Curren PERIOI Annual review of all i Compr< Ray Micl and t Opinion in •" 5ONTOLOGY idvances • Evaluation of key references ^hensive listing of papers Editors mond A Yukna, lael G Newman, Ray C Williams STUART J FROUM D.D.S., PC PER1ODONTIC5 IMPLANTOLOGY THE ROCKEFELLER APARTMENTS SUITE 1 CD (7WESTS4TH STREET NEW YORK. NY 10O19 FAX (212) 246 7599 (212) 586-4209 GS CURRENT WTPlSJiPPB ol^ 1 tLlNL-Ii • Periodontal regeneration Stuart Jay Froum, DDS,*1 and Cynthia Gomez, DDS+ "Veterans Administration Hospital, and +New York University Dental Center, New York, New York, USA This paper reviews the current clinical and histologic literature in the field of periodontal regeneration. Various procedures and agents that have been used to attain regeneration and new attachment are reviewed, including open flap debridement, root conditioning, the use of bone grafts and bone substitutes, guided-tissue regeneration, coronaily positioned flaps, and a combination of these. Future directions for clinical and research efforts are discussed, with emphasis on growth factors, their delivery, and enhancement of the healing response. Literature identifying factors that will aid in the regeneration of lost periodontium is reviewed and critiqued. Current Opinion in Periodontology 1993:111-128 Periodontal regeneration The ultimate goal of periodontal therapy is the reconstruction of supporting tissue lost as a result of disease. In the past, conflicting reports and terminology following various attempts at regeneration led manv to question whether this goal was attainable. The .standardization of precise definitions of terms involved in the healing phenomenon (ie, regeneration, repair, new attachment, and reattachmentJ has resulted in a more accurate assessment of the healing response [1|. This accuracy, together with improved measurement techniques, has allowed critical evaluation of new attachment procedures, with the recognition that periodontal regeneration and new attachment are possible following various surgical procedures [2-8], Regeneration is now denned as the reproduction or reconstruction of a lost or iniured part' [1]. Periodontally. this definition implies the formation of new bone. new cementum. and a functional v oriented penodontal ligament. Regeneration therefore may only be assessed by histologic data. New attachment is defined as the reunion of connective tissue with a root surface that has been deprived of its periodontal ligament. This occurs with the formation of new cementum with inserting collagen libers [1|. Tiiis again is a histologic phenomenon. The histologic determination and differentiation of regeneration, new attachment, or repair has been facilitated by the calculus notch marker system (31. This system assures that the pretreatment root surface being studied has been altered by disease and is free of periodontal ligament fibers. The submerged root model system has also been instrumental in determining whether the healing response is by regeneration or repair (91. • New clinical attachment (pocket closure) may occur as a result of regeneration, new attachment, or repair. However, from a clinical standpoint, this attachment implies a gain in clinical attachment level as measured by a decrease in probing pocket-depth, when measured from a fixed reference point. Current clinical studies use attachment-level gain, gingival shrinkage, and pocket-depth reduction and reentry or tissue probing bone measurements to describe the clinical response. Various procedures and agents have been used to attain periodontal regeneration. This article will review current literature relating to periodonta! regeneration by organizing these efforts into the following topics: open flap debrtdement (OFD): Abbreviations CPF—toronallv positioned flap; DFDBA—decalcified ireeze-dned bone allogratt: FDBA—treeze-dned bone .illosratt: CTR—guided-tissue regeneration: OFD—open tlap debridement; PTFE—polytetrailuoroethvlene. © 1993 Current Science ISBN 1-870485-58-0 ISSN 1065-626X 111 112 Periodontology root conditioning; bone grafting and hone substitutes; guided-tissue regeneration <GTR) (membranes ); coronallv positioned Haps iCPFs); combination procedures; and future directions. Open flap debridement The OFD procedure has been shown to clinically reduce probing pocket depth with a gain in probing attachment level. This effect was contrasted with resective procedures that also resulted in a decrease in probing pocket depth, but with a loss of attachment level [101. Fig. I. Hematoxvlin-eosm stain ixlO). Note sort-tissue closure within notch, and shape and position of alveolar crest. \From Stahl and Froum |)18|; with permission.) The OFD procedure is a viable clinical procedure, and often serves as a clinical and histologic control in assessing various regenerative models. Studies have shown that the OFD procedure results in a decrease in gingival inflammation, bleeding on probing, and pocket depth [6,111. However, a recurrence of pocket depth and bleeding on probing was shown to occur with OFD 112.13). Overall, various clinical studies using OFD procedures have shown an average gain of probing attachment level ranging from 1.1 to 1.4 mm |l4.1S,l()(. Conflicting results were observed with reentry of sites treated by the OFD procedure. Variable amounts of bone fill were reported [14.17,18.191. Fill of osseous defects ranged from O.T to 3 mm I U.2U-22]. Plaque control and professional maintenance seemed strongly correlated to (he degree of osseous response [231 and new clinical attachment [14]. Human histology suggests that the retention of gingival fibers results in reattachment [24]. With injury to the root surface, only limited reattachment can be expected, and apical migration of the functional epithelium occurs !24l. Histologic research has demonstrated that the primary healing response to the OFD procedure is a soft tissue adhesion of the flap to the root, with the formation of a long junctional epithelium with little or no new cementum (25-27). Schroer et al. [28*] evaluated the clinical response of facial grade it furcations in molars comparing closed versus OFD procedures. The authors found a gain in probing attachment level of 0.6 mm in the midfurcal area in the scaling and root planing groups. This contrasted with a loss of 0.46 mm in the OFD group. The OFD procedure is often used in periodontal therapy in areas of shallow to moderate periodontal defects. Deep intrabony and furcation lesions may be more effectively treated by other regenerative techniques. Citric acid conditioning Citric acid conditioning of the root surface is based on the premise that demineratizing the root surface exposes the collagen fibers present in dentin or cementum. which form a barrier against epithelial migration. It has been demonstrated that a root surface affected by periodontal disease undergoes pathologic changes manifested by hypermineraiization reported to a depth of 40 to 60 |im [291, and also by binding of endotoxin [301. Establishment of a biologically acceptable root surface involves removal of plaque, calculus, and affected cementum. Studies have shown that instrumentation of the root surfaces with hand or ultrasonic devices results in the formation of a smear layer (31). This layer may act as a barrier to connective-tissue attachment to the root. Application of a demineralizing agent removes the smear layer, thereby exposing the collagen fibers present in cementum or dentin [32]. The exposed collagen fibers are chemotactic to fibroblasts and serve as a substrate for attachment, growth, and synthesis of new connective-tissue attachment on previously diseased roots (331- These exposed fibrils were thought to allow interdigitation ot collagen fibers from repairing connective tissues (3-*JIn addition, adhesion of the wound coagulum or granulation tissue to the root surface is enhanced by demineralizing agents. The fibrin present in the blood clot of the early wound links with the collagen in the root surfaces, forming a stable bond. Periodontal regeneration hroum and Gomez \ 13 which prevents apical migration of the epithelium [351. Fig. 2. Higher magnitication ol crestal area from site shown in Figure 1 (x 25). Note resorption at the facial aspect of the labial plate, osteogenesis at the periodontal aspect of the plate, and cementogenesis at the root surface. Also note the tip of the crest tilting toward the root. {From Stahl and Froum [118|; with permission.I Early animal model studies of previously denuded root surfaces treated with citric acid demonstrated new eementum, fiber linkage, and a minimal amount of alveolar bone growth [36—38). In humans, the results ot citric acid conditioning of the root surfaces have been varied [39—ill. Doubleblind clinical evaluations showed no benefits to the use of citric acid conditioning [-t2j. Eschler and Raplev [43! noted that citric acid alone was not effective in removing plaque and calculus. Hanes et al. [-*-+"] noted that root planing was necessary before citric acid treatment. In another study, Hanes et at. [-n"l noted that citric acid removed the smear layer on hand-instrumented roots, enlarged dentinal tubules, and increased tubule diameters. LeBahn et al. h6*| agreed with Hanes et at., demonstrating that citric acid removed the smear layer and opened the dentin tubules. Sterret et al. [-t7] claimed that the peak solution for citric acid was pH l.-il for dentin demineralization. Chaves et al. \-i8"\ found that citric acid did not alter the effects ot scaling and root planing and caused no penetration of dentin tubules. These findings were contrary to those of Hanes [44",45**] and LeBahn [46*1. The results of studies using citric acid and root conditioning are still inconclusive, and biologic mechanisms are still unclear Earlier studies documented the attachment of penodontal-ligament cells to root-planed roots, even with the smear layer [211. At present, while adverse effects of citric acid root conditioning appear limited [49-511. further studies are necessary to ascertain true clinical or histologic advantage. Bone grafts and bone substitutes An excellent review by Bowers and Reddi [52"1 of some current approaches and future directions for periodontal regeneration was recently published. i Although omitted from this paper, autogenous intraoral bone grafts have also been shown to facilitate successful regeneration l53-:>6].) An excellent review of the use of freeze-dried bone allografts (FDBAs) was recently provided [571. Mellonig et ul. [58*! used bone contaminated with HIV to demonstrate that demineralization and treatment with a virucidal agent inactivates HIV and renders the allograft safe for human use. The authors [58**1 also provide a detailed explanation of the time-related cellular and molecular events in the bone-induction process. Future techniques and materials are mentioned, including the use of morphogenetic proteins produced by recombinant- DNA techniques. A recent paper by Bowers et al. [S9"l. using the calculus notch marking system, histoiogicaliv evaluated 36 submerged defects in eight patients and SO nonsubmerged defects in six patients with famonth biopsies. The findings indicated that osteogenin combined with decalcified freeze-dried bone allograft (DFDBA) enhanced regeneration in a submerged environment. In nonsubmerged defects, DFDBA and osteogenin and DFDBA alone formed significantly more new attachment than either tendon-derived matrix plus osteogenin or tendon-derived matrix alone. Also, osteogenin did not impair normal lymphocyte blastogenesis 6 months postsurgery. Drury and Yukna [60*] used nylon mesh chambers placed in surgically created windows in the mandibles of baboons to determine if tetracycline rehydration of FDBA would enhance bone regeneration compared with rehydration of FDBA with sterile water. Threeand 5-week histology demonstrated much greater C>5 times) new bone formation with tetracyclinerehydrated, compared with water-rehydrated FDBA. The osteoinduction capacity of demineralized bone matrix was confirmed in a recent paper bv lsaksson and Alberius [(•>!•). 114 Periodontology ^ 1 FIJJ. I. Fop left, Mandibular in< isors with orthodontk brae kets plat ed prior to surgery Top right Surgii al flap exposing osseous defei i Bottom left, Following dHcu ,irul root ilchriilrinrr: implications of citric acid (pH = 1) with (nttnn >.v\.ihs toi i minutes. Bottom right Coronal!} an< hored flap with silk sutures. A review oi studies using alloplastk materials suggests thai these materials result in improved probing-depth reduction, decreased defect depth, and added hulk ol'ilu osseous structures preseni However, use ol either beta tricalcium phosphate or hydroxyapatitt does noi result in regeneration of the periodontium 121 From a clinical stand point. FDBA showed a greatei improvemeni in clinical parameters t hnn porous hydroxyapatite in intraosseous defects, ie osseous fill. 2 1 mm versus 1.3 mm: new clinical attachment gain. 2.2 mm versus 1.3 mm; decrease in probing depth, 3.0 nun versus I i mm respectively |( -I Recently, Galgut el at [63*1 reported on i-year clinical results comparing 58 sites treated with nonre sorbuble hydroxyapatite and 59 sites treated with OFD Ai the tih year, reduction in pocket depth w.is significantly greatei For sites treated with the tmplam material From years 2 n> t. gains in probing attai.htin.-nt improved with the hydroxyapatite treated ^itrs but deteriorated in tlir control sites Extraction ol a hopeless tooth ! yr.it following treatment with a porous hydroxyapatite implant material vv.is reported b\ Mellonig [64*|. Histologically. ;i fibrous ct>nnective-tissue attachmem !o a planed root surface was "strongly sugges tive of a new attachment." However, as the author [6^] points out, "the root surface was noi notched in calculus prior to grafting" and new at tachment "could not be confirmed." Previous his tology on notched root surfaces "demonstrated in creased bone mass bui healing by long junctional epithelium withoul new attachment.' Frank ci al [66**] reported on bone formation following implantation or three bioceramic powders into human periodontal lesions. The) conclude thai bone- formation around the three bioceramics occurred through similar mechanisms ;H the ultrastaicrural level. However, by 6 months, small microsized hydroxyapatite had a significantly greater amount ol peripheral bone compared with the other ceramics The authors conclude that ens tal size may be important in determining the el Periodontal regeneration Fmum tma Gomez 115 ficiency of bone formation. They recommend that the manufacturers indicate the crystal size or the various bioceramic powders. Partide size or' the most commonly used alloplasts has been shown to be consistent and ranges from 100 to -(00 \im [67]. Two recent studies tested two different alloplastic graft materials. In the first studv. Wilson and Low 1(>8#| compared tour bioactive ceramic materials. All tour ceramics allowed bone repair but Biogiass (Bioglass Research Center. Gainesville, FL) appeared to limit the downgrowth of epithelium. Shamiri et ai. [69*1 recently published a clinical study comparing HTR polymer versus OFD in 30 intrabony detects in IS patients. Their findings demonstrated that whereas pocket reduction was significantly greater initially in the implanted Mte.s versus control sites, there were no significant differences in pocket reduction responses at 12 months postsurgery. Histologicallv. HTR appears to perform similarly to other alloplastic materials, being well tolerated but of limited regenerative potential [~0]. Cuided-tissue regeneration tn 19~(i. Meicher [~1| suggested that healing in the periodontal milieu was determined by the cell type that repopulated the wound surface. If epithelial ceils were allowed to repopulate the wound, a long |unctional epithelium resulted. Cells from the gingival connective tissue caused resorpiion of the root surfaces, while bone-derived cells brought about ankylosis. New attachment would result if cells from the penodontal ligament were allowed to repopuiate the wound area. More recently, in two separate studies. Meicher et ai. [*72| and Meicher and McCulloch [""31 demonstrated that cells derived from bone also have the potential to mediate a regenerative response This concept of selective cell repopulation or GTR influenced Nyman et ai. ["4.751 to use occlusive barriers in periodontal healing studies. Recently. Duff [76*1, Dowell et ai. [77*1. Phillips and Palou [~8»|. Caffesse and Becker P9"l. Mmabe |S0"|. and Nyman I81"l wrote reviews on GTR and the use of barrier membranes. Collagen s effectiveness as a potential barrier received much attention tn a number of studies. The rationale tor the use of collagen is that type I collagen is the main constituent o\ connective tissues in the periodontium; collagen is a substrate for adhesion, migration, and proliferation, and aids in the orientation of penodontal ligament ceils {821: it is hemostaric: it is available in many forms; and it is weaklv immunogenic in humans I83|. Fig. 4. Overview of root surface coronal to calculus notch at tooth #31, 18 weeks arter surgical procedure thematoxvlineosin stain). Note root surface resorption apical to junctional epithelium. Arrow points to apical position of lunctional epithelium. (From Stahl and Froum [119"l: with permission Flanary et ai. [84*] evaluated the use of Biobrane Temporary Wound Dressing (Withrop Pharmaceuticals, NY), a synthetic skin substitute in paired class II furcation defects in mandibular molars. They concluded that Biobrane hud limited clinical application in GTR. Galgut et ai. (85*) evaluated the histologic response of Millipore * Millipore Corp, Harrow. Middlesex. UK), Gore-Tex (W.L Gore. Flagstaff. AZ) and two biodegradable materials when placed transcutaneously in rats. Quteish and Dolby [86*] developed and tested a biodegradable collagen membrane on paired defects in humans. The 6-month clinical evaluation showed a gam in attachment compared with OFD alone. Paul et ai. [H7«| used Collistat (The Kendal Co.) in paired class II furcation defects in seven patients. Sites were reentered in 6 months. Warrer and Kamng i88*| evaluated Tisseel Ummuno AG. Vienna. Austria), a two-component adhesive system with fibronectin. on four dogs. Tisseel failed to facilitate repopulation of the root with penodontal ligament cells on a predictable basis. Tal and Pitaru [89*1 used collagen membranes in dogs. New 116 Periodontology cementum, new bone, and new periodontal ligament (at the apical half of the defect) were seen at 30 days. Lekovic et al. [90*j used autogenous periosteum in class II furcation defects and reentered the sites in 6 months. Yukna [91*1 compared Gore-Tex with freeze-dned dura matter in class II furcation defects in human mandibular molars. Kon et al. 192"| compared the healing and regenerative capacity of the periodontal ligament using resorbable (Vicryl: Ethicon. East Brunswick, NJ) and nonresorbable (Gore-Tex) membranes in dogs. The nonresorbable membranes showed better regeneration potential than the resorbable ones. Metzler et at. [93**1 evaluated paired class II furcation defects in maxillary molars treated with OFD or placement of Gore-Tex memDranes. They concluded that results in class II furcation defects in maxillary molars were not predictable. Pontoriero et al. [94**| created three types of defects in dogs and treated these defects by OFD and placement of Gore-Tex membranes. The sites were evaluated after 4 months. The authors concluded that GTR may result in new attachment in furcations, but the size of the defect and the degree of bone loss determined the amount of tissue regeneration. Flap recession was cited as an obstacle to regeneration using the Teflon membranes. Caton et at. [95**] evaluated the use of GTR in onewall interproximal defects in monkeys. The authors concluded that the position of the barrier defined [he magnitude of coronal regeneration. Moreover, regeneration is the result of participation of cells from the periodontal ligament and alveolar bone. This finding was similar to that of Melcher [72] and Melcher and McCulloch [73]. Lu [96*1 studied the topography of root trunks and found that 94% of the molars studied had a concavity on the trunk that prevented the membrane from adapting to the root. Wenzel et al. [97*1 noted that bone changes after GTR correlated best with clinical measurement of attachment gain when assessed with digital subtraction radiography. Bragger et al. [98*1 used computer-assisted densitometer image analysis and found it to be a noninvasive. objective method of obtaining information on remodeling of alveolar bone at sues treated by GTR. Gottlow et al. [99*1 noted that GTR can result in gains of attachment, which can be maintained for periods over S years. Various histologic studies performed used different defect types and morphologies. These studies •*eem to suggest that successful regeneration was hampered by flap recession. Clinical studies concurred with this observation. Exposure of the membrane led to incomplete soft or hard tissue fill of the defects. Three separate abstracts reported colonization or bacterial contamination of the Gore- Tex material that was exposed to the oral cavity [100-1021. The importance of defect morphology in the resultant healing cannot be discounted. Most of the studies stressed the impact of the size of the defect on the outcome of GTR procedures. This issue may relate to the adequacy of soft-tissue closure or complete coverage of the defect by the membrane barrier. Coronally positioned flap The rationale for employing CPFs in regeneration is based on the biologic principle of delaying migration of epithelial cells, thereby allowing the fibrin clot and connective-tissue cells to repopulate the rcK)t surface. By placing the flap in a more coronal position, preferably against the enamel of the tooth, the epithelium is displaced at a greater distance from the root surface [1031. This creates a space, allowing for cells from the periodontal ligament or alveolar bone to repopulate the wound and affect a new connective-tissue attachment (104). Coronally positioned flaps have been used mainly in conjunction with citric acid conditioning or demineralized bone allografts. When treated with the combination of CPF and allografts. turcal defects in dogs were decreased or completely closed [I05|. In humans, furcal defects were treated with citric acid (pH=l. 3 min) and CPF. and were compared with defects treated with CPF. citric acid, and allografts. There was a decrease in pocket depth in class II furcation defects from 5.5 mm to 2 mm. due to attachment gain rather than recession. Bone allografts did not enhance bone formation: only 48% of class II furcations were completely closed [106], Evaluation of the CPF and citric acid conditioning in dogs showed an enhanced flap adaptation to root surfaces and new cementum in 21 of 23 furcations in one study [107|. New connective-tissue attachment with CPF with or without citric acid occurred in 13 ot 1-4 sites evaluated in another study 1104). Connective-tissue adhesion was observed if the flaps were placed in apposition to the roots [10H|. Resorption of the roots by the cells of the gingival corium was a variable rinding, xs was ankvlosi.s [ 10-+I. Periodontal regeneration Froum and Gomez 117 Games et at. (109*1 evaluated the response of class III furcations treated with citric acid and CPF or with citric acid. CPF. and allografts. They noted that complete soft-tissue coverage of the furcation was critical for success, with only one of 14 nongrafted and three of 13 grafted defects showing complete soft-tissue clinical closure. In another review. Games and Garrett [110") presented the healing responses of beagle dogs to CPF. Successful regeneration once more depended on adequate soft-tissue coverage of the defects. The most dramatic results were observed when the clinical crown was completely covered by the soft-tissue flaps. Even when complete soft-tissue coverage was not obtained, positive results were reported. Combination techniques In an attempt to produce more predictable results, vanous studies have attempted to combine the biologic principles and elements of different regenerative procedures. Combining the techniques of GTR, root conditioning, and composite grafting showed a clinical advantage of the membrane-graft group over the membrane alone [111]. Handelsman et til. [112"] compared the use of polytetrafluoroethvlene (PTFE) membrane (W.L. Gore. Flagstaff. AZ) in the treatment of intraosseous defects with and without prior root conditioning wuh curie acid <pH = 1. for 3 min). Although in both groups clinical parameters improved, there were no statistically significant differences between the two groups. Citric acid root conditioning did not enhance clinical findings when used with PTFE membranes. Anderegg et al. (U3"l compared the use of a membrane barrier alone (PTFE) or in combination with DFDBA in the treatment of class II and III furcation invasions. Six months posttreatment, surgical reentry on each site (2"T class II and three class 111 furcations • showed no difference in attachment level changes but greater reduction of probing depths in the sites treated with DFDBA and membrane versus membrane alone. Although hardtissue changes were comparable for alveolar crest resorption. there was a statistically greater horizontal and vertical bone repair in defects treated with the DFDBA and membrane combination. However, the authors noted that only four sites of 30 closed completely. This finding differed from six of l-» noted in the previous study [111]. A recently published abstract [1HI compared treatment of two and three-wall bony defects after GTR with and without hydroxyapatite implants. Conventional surgery served as a control group. There were no statistically significant differences among the groups and among the 6 to 12 months' results. The addition of hydroxyapatite implants when using membranes snowed no advantage. Another abstract presented by Vamada et al. 1115] compared the effects of the use of a PTFE barrier membrane with and without DFDB in created class III furcation defects in four mongrel dogs. Results suggested the use of DFDB in coniunction with the membrane can support regeneration of new bone and penodontai tissue. A recent study by Warren and Karnng [116*1. using surgically created horizontal defects in three dogs compared a Teflon membrane (Zitex: Norton Chemplast. New York) plus a fibrin sealant <Tisseel) with the membrane, sealant, and Kielbone (Braun; Melsungen. Germany). Histologic analysis after 3 to 4 months of healing failed to demonstrate consistent penodontai regeneration in either of the two groups. Combined Teflon membrane and porous hvdroxyapatite was used by Stahl and Froum [IP") in the treatment of seven vertical lesions at seven teeth in three adults. Notches were placed in calculus and blocks were taken 10 to 28 weeks postsurgery. Histologically. rwo sites exhibited closure by long junctional epithelium. The remaining five sites showed gingival recession to be apical to the calculus notch (or epithelium in the notch). However, cellular cementum was seen just apical to the notch. Within the osseous crater, increased bone mass and functionally oriented penodontai ligament were seen. Two recent histoiogic studies explored healing of human suprabony defects, which may be the most difficult type of defect to regenerate. In one study, Stahl and Froum 11181 applied a Teflon membrane over four suprabony lesions and sutured flaps as coronally as possible using orthodontic brackets as anchors. Using a calculus notch marker. 2- to 3-month block sections showed new cementum and functionally oriented fibers in three of four membrane-treated sites and immediately apical to the notch in one sue (Fig. IV Cementogenesis adjacent to supracrestal osteogenesis was seen with the new bone filling the space created by the membrane (Fig. 2). In a second study [119"*l. seven suprabonv pockets were treated with debndement. citric acid root demineralization. and coronal positioning ut the marginal flaps with orthodontic brackets xs .in118 Periodontology chocs i Fig. 3> Block sections at ~ and 18 weeks demonstrated histologic evidence of new cementum with Functionally inserted fibers within the calculus notch in all coronally anchored sites < Figs. •\ and 5). Fig. 5. Site of calculus notch in specimen shown in Figure 4 (x 25). This was located apically to root surface resorption. Note osteogenesis, cementogenesis. and oriented periodontal ligament fibers inew attachmentl in the calculus notch [From Stahl and Froum |119"]; with permission.I Future directions Several years ago recommendations were made for future directions in clinical practice and research into regenerative procedures [2]. Many of the "combination therapy" regenerative procedures discussed in that review now appear to offer the opportunity for enhancing clinical results while improving the predictability of the regenerative response. A combination of CPFs in conjunction with membranes, grafts, or root conditioning has demonstrated promising clinical results (Figs. 6 and 7), When using combination-type procedures, one must avoid the "throwing everything in" philosophy, which may be no more effective (or even less effective) than any of the component techniques used individually. This certainly was the case in a studv by Wikesio et al. [120**!. Test protocol on created supra-alveolar defects included root surface treatment with citric acid and tetracycline, followed by placement of a composite graft including hydroxvapatite. freeze-dried decalcified bone, tetracy- Uine, and finronectin with flaps placed and sutured to cover most ot the crown. Controls included citric acid root conditioning and similarly placed flaps. Six-week histologic results showed that the composite graft protocol did not offer any advantages over citric acid alone for periodontal reconstruction. Regeneration is a complex phenomenon that depends on a coordinated response from several cell types, extracellular matrix, and proteins. The more that is understood about the biology of events and mechanisms regulating periodontal tissue healing. the easier it will be to transfer this knowledge to clinical techniques and to achieve more predictable regenerative results. To this end, Wang and Somerman (121"] presented a review of the proteins and factors considered essential for the maintenance and regeneration of penodontal tissues. A review of extracellular matrix, growth, and morphogenic factors was presented by Ripamonti and Reddi [122"]. Further examination of osteogenin and recombinant human bone morphogenetic protein-2B was presented by Luyten et al. 11231. Several recent studies examined other growth factors related to their possible use in periodontal regeneration. A combination of platelet-derived and insulin-like growth factors was shown to .enhance regeneration of the periodontal structures in periodontitis-affected teeth in beagle dogs [124"|. The use of recombinant human platelet-derived growth factor and insulin-like growth factor tn debrided, experimentally produced lesions in monkeys (Rutherford et al. [125"]) suggests that further study of these growth factors is needed to treat adult periodontitis. Matsuda et al. [126"] demonstrated that recombinant human platelet-derived growth factor and insulin-like growth factor stimulate mitogenesis. proliferation, and chemotaxis of periodontal ligament fibroblastic cells. Moreover. pH recombinant human platelet-derived growth factor also stimulates collagen synthesis by periodontal ligament cells. Takeshita et al. [IT7] demonstrated that interleukin 13 is a regulatory cytokine involved in the regeneration of the human periodontal ligament. Using growth factors in periodontal regenerative procedures requires a biocompatible and effective delivery system. To that end. various bone graft materials and gels have been used. Decalcified freeze-dried bone allograft combined with osteogenin. a bone-inductive protein, was used in submerged and nonsubmerged defects in humans Periodontal regeneration Froum and Gomez 119 Fig. 6. Top left, ( lass II furcation on tooth #1'). Top center, Furcation detect exposed- Top right, Probe penetrates 5.0 mm horizorttally. Middle left. Gore-Te\ (W.L. Gore, Flagstaff, AZ) periodontal material positioned and sulured. Middle center Coronal flap positioning utilizing Gore-Tex sutures Middle right. Healing open probing new atu< hment following membrane remov.il. Bottom left, Coronally sutured flap. Bottom center, Reentry 16 months postsurgery showing hone filling ihe furcation. Bottom right Tooth #ll), 2 years postsurserv [59"1. Ripamonte el at [ilH*] used resorbable and non-resorbable hydroxyapatite rods with and without osteogenin in intramuscular sites in baboons. Only nonresorbabie hydroxyapatite with and without osteogenin showed differentiation of bone. Osteogenin did not increase the amount ol bone An abstract by Yewey et a!. [129*1 used .i biodegradable polymer (AtrigeL Atrax Lab Ine. Fort Collins. (X)) to release in vitro fibronectin and fibrohlasi growth factor. The results may hold promise for this method as a delivery system. Another future direction of regenerative research \\,i> discussed by Wikesjo et <il 1130"! in their re- Mew of early healing events in periodontal repair. The authors note the importance of establishing and maintaining a root surface-adhering fibrin clot to prevent apical migration ol gingival epithelium and thus favor connective tissue attachment. Another attempt to prevent apical migration of epithelium during initial stages of wound healing was studied in dog.s by Fitaru et til [131"). Using hilayered collagen harriers enriched with fihronectin and heparan sulfate, the authors repopulated 95% of the occlusal-apical length of created defects in dogs by connective-tissue cells I .M) Puriodontology • I Fig. 7. Top left, Eight millimetei probing depih on the mosi.il oi tooth #5. Top center Mucoperiosleal flap reflected .md mcsi.il defeel and furcation probed Top right, Defecl depth H rum Middle left, Following debridement, fill of the defeel with decalcified freeze dried hunt' allografl under Gore-Tex (W.I Gore. Flj^si.itt. A/> periodontal ni.iirii.il. Middle center, Memhr.ine positioned and sutured over the delect. Middle right, One year reentry following membrane removal. Note defeel fill Bottom left Two y<J.ir probing w i th apparent K d i n in t linn .if attai hmenl (rxx kel closure). Conclusions Periodontal regeneration has been demonstrated to be pcxssible. However, to date, no single technique has been shown to IK- predictable for all defects. Identification of the healing events and factors that control or enhance these events has led to development of clinical techniques and new agents that we hope will improve predictability. Testing combinations of the various procedures has shown that some do not enhance (and may even inhibit) healing whereas others hold promise for improved responses With more research data, regenerative treatment may becomt site-specific, with certain growth factors, root conditioning agents, and membrane or Hap designs used with spe rifle defect types. At present, nonresorbable Teflon membranes have shown the best results in fin cation defects Research using membranes or citri< acid root conditioning with CPFs has shown the potential foi supracrestal attachment Certainly, resorbable membranes and delivery systems for growth-regulating proteins lie in the near Future. We hope the studies cited in this paper will bring us closer to the reality of predictable regeneration. References and recommended reading P a p e r s 'it p a r t i c u l a r i n t e r e s t , p u b l i s h e d w i t h i n i h i - .• iirui.il | j f r n n . l uf review have been highlighted as • i )i -.|x-c i.il inleresi • • < >1 ' " U l N t . M u t i n y ii i l i !• "SI I IHKI \ \ i . . DMIMHUI. WH. MCFAU VFT, < > 11 \KS TJ. I'Kh ll\KH IF: ( i l o s s a n cil pcriiHluni.il ii'rms I PeriotUmtuI I I A \ I I X K KB Regeneration procedures In proceedings ol the world workshop in <.linic;il pcriodoatics. Edited tu Sevin> M. Becker \\. Kornrn.in K. PrincelcMi: American Academy r,l Periodonlnlogy: I989:V1 I VI 20 Periodontal regeneration Froum and Gomez 121 10 11 12. 13 \-i COLE RT. CRICGER M. BOOLE G. EGELBERG J. SELVIC kA Connective tissue regeneration to peruxlontallv diseased teeth I Penodont Res 1980. IS: 1-9. Si LLI\ -\S HC. DR^GOO MR Regenerative techniques in penodonul therapv Dem Cltn \ortb Am VPb. 20:131—153 \\ Miv AH An evaluation of rcparative procedures in penudontaJ surgerv hit Dent I 1971, 21 -KJ—iiO. Mt'lRTHUN MR The current status ot new attachment therapy. J Penodontoi 1981. 52:529-5-4*1 EGELBERG I Regeneration and repair of periodontal tissues. / Pentnii»u Mvs [987. 22:233-242 FROl'M S: Clinical attempts at penodontal regeneraiion. .W Slate Dent I 1<)H<) 44 •*•*—o BOWFK-S GM, CHADROFF B, CARNEVAL R. MELLOMG J, CORIO R. EMERSON [. STTVFNS M. ROMHERG E: Histologic evalua- (ion of new attachment apparatus lormation in humans. / Penodontol 1989. 60:664-674. ROSUNC B. N'VMAN s. LJNUHE J TTic healing potential of the periodontal tissues following different techniques of penodonial surgcrr in plaque tree dentitions. / Cttn Pertndimioi 1976. 3 233—250. [SIDOR F. KARRIM*. T. ATTSTROM Z. The effect of root planing as compared to that of surgical treatment. J Clin Penodontot 19H4. 11 669-681. CXSE.N C. AMMON W. VAN BELLE C: A longitudinal study compannn apicallv repositioned tlaps with and without osseous surgery. />;; / Pentxiont Rest Dent 198*), 4:11-31. SMITH 1). AMMONS W. V^N HELLH a A longitudinal study of the periodontal status comparing osseous surgery with flap curettage I Results after (> months. J Penodonlot 1980. si 567-3-5 FROUM S. CURA.M I. THULLER B. Penotlontal healing following [lap dcbniJernent procedures [ Clinical assessment of soft tissue and osseous repair. / Penodonlol 19H2, 53:8-14. 15. DLRW1S -V CHA.\1BERUUN H. GMtRETT S. RENVERT S. KGELBERG I Hcilinp after treatment of penodontal intraosseous detects IV. Effect of a non-resective vs. a partially resective approach. J Clin Penodonlol 198S. 1(), REJJVEKT S. BADEHSTEN A. NlLVEt'S R. EGELBERO J. Healing after treatment ot penotlontal intraossrous defects. I. Comparative study of clirucal methods. / Clin Penodontol 1981. 8:387-399 I" RENVERT S. EtiELBEJKi I: Healing after treatment of periodontal mtraosseous defects II Effects of citric acid conditioning of the root surface. / Clin Pent nionlnt 1981, 8:-4S9—173. 18 ElLECAARD B. LOE H. New attachment of penodontal tis- IUCS aner treatment of intrabonv lesions. / Penoduniol 1971. 20 HIATT W, UFL^TO D. HlATT W" LINDFORS F The induction of new bone and cementum formation. V: A comparison of graft and control sites in deep infrabony lesions hit I Periodont Rent Dent 1986. 6:8-21. 21 POLSON A. HEML L: Osseous repair in infrabonv penodontal defects / Clin Penodontot 19"8. S: 13-23 12. F.GELBERG I: Regeneration and repair of penodonul tissues J Periodonl Res 1987. 22.11^1-12. 2.1 ROSUNC LS. NYMAN S. LINDHE J The effect of systematic plaque control on bone regeneration in intrabonv pockets. J Ctln Penodontol 1976, iiS-^i. 2-i. STAHL S. LEVINE H Repair of penodontal flap surgery with retention of gingival fibers / Penodonlot 1972, 43:99—103 25. LlSTCMKTEN M. ROSENHKBIJ M Histologic repair of new attachment procedures in human penodontal lesions. I Penodontol 1979, 50:333-3-4-4. 26. STAHL S. FROI.'M S. KUSHNER L Periodontal healing of open (lap dtbridemem flap procedures. II. Histologic observations. J Penodonlol 1982. ^i 15. 27. CATON I. ZANDER H: The attachment between tooth and gingival tissue after penodic root planing and soft tissue curettage. / Penodonlol 19Tl), S0:-l02. 28. SCHROER M. WAHL T. HLTCHENS L. MORlARTf I. BERGES- • HOLTZ B: Closed versus open debridement of facial grade II molar furcations. / Clin Penodontol 1991. 18323-329. Twenty-hve teeth with facial class II furcation problems were treated with scjling und root piamnji and were evaluated at -i months. Twelve i>( 25 teeth were treated *uh OFD- 13 were treated with scaling and r<xjl planing. There was a decrease in probing depth. jjln8lv:1' inflammation, and Plaque Index al lb months. Scaling and roo! planing groups gained probina auachnient level bv 0.6 mm; OFD groups lost U -IO mm 29 SELVir, K. HALS D: Periodontallv diseased cementum studied by correlated microradiography. electron-probe analysis and clcctromicroscope. j Periodont Res 1977. 12:419—»29 19 FLLEGAARD ti. K.VRR1SG T. DAVIS R. LOK H: New attachment After treatment ot Lnfrabony lesions. / Penodontot 1974. 30. 31. 32. 33. 34. 35. ALEO J, I>ERENZIS T. FAHBEH H; in vitro attachment of human gingivai hbroblasts to root surfaces / Penodonlol 19~5 46639-645. JONES S. LOZDAN I. BOVDF A Tooth surfaces treated in sicu with penodontal instruments SEM studies Br Dent J 1972. 132:57-<M. POLSON AM. FREDERICK GT LADENHEIM S. HANES PI The production of a rool surface smear layer by instrumentation and its removal by citric acid. / Penodontoi FERNYHOLTGH W. PAGE R: Attachment, growth and svnthesis by human gingival ribroblasts on demuieralizcd or fibronectin treated normal and diseased tooth roots, j Penodontol 1983. 54:133-140 LOPEZ Nl: Connective tissue regeneration to penodontallv diseased roots, planed and conditioned with cunc acid and implanted into the oral mucosa / Penodontoi POLSON AM. PROVE MF Fibnn linkage: A precursor for new attachment. / Penoduntol 1983. *4:l4l-U7 122 Periodontology 36 REGISTER A. m RD1CK F Accelerated reattachment with cementogencsis to dentin. demineralized in situ. II Defect repair, / Penodontoi Wb. 47:497-505 5"l RlRIE CM. CRitiGER M, BOGLE G. ECELBERG I, SELVIG K Healing of pcriodontal connective tissue following surgical wounding and application of citnc acid in dogs. / Penrjdonl Res 6980 15:314-327. *H NOVELS R- EtiELBERG I The effect of topical citric acid application on the healing of experimental furcation defects in dogs. III. The relative importance of coagulum support, flap design and systemic antibiotics / Penoctont Res 1980. 1V55! j9 COLE KT. CRIOCER M. BOOLE G. EGELBERC I, SELV1G K: Connective regeneration to penodonully diseased teeth. / Penodont Res 1980, 15:1-9. 4(1 FROUM SJ, KUSHNER L. STAHL SS Healing responses in human intraosseous lesions following the use of tie bride me nt. uraltinx and citric acid root treatment. II. Clinical and histolojjtc observations, one year postsurgcry. J Penodontoi 1983, 54:325-338. t) REWFHT S. EGELBEKC I Healing after treatment of periodontal mtraosseou* defects. II. Effect of citric acid conditioning of the root surface. j Clin Penoaontol 1981. 8:459—473. 42. MOORE J. ASHLEY KP, WATERMAN l A The effect on healing of application of citric acid during replaced flap surgery j Clin Penodontoi 1987. 14:130-135. •i* E.SCHLER B. RAPLFY I Mechanical and chemical root preparation in vitro Efficiency of plaque and calculus removal / Penodontoi 1991, 62:755-760 -H HANES P. POLSON F. FREDERICK T Citnc acid treatment of •• penodontitis affected cementum: a SEM study. J (Jin Penodontoi 1991. 18:567. I'ementum surfaces from roots of extracted human teeth from ar- C-JS Ix'neuth penoduntal ligaments (normal) and calculus deposits i penodnntitis-alfectedt were evaluated. Oniv scaling was done on affected roots Hoth groups were treated with citnc acid (pH"l, 3 mini. Citric acid treatment of normal roots exposed a hbnllar collagen substrate, wnile penodontitis-attected roots were not allered in appearance by citnc acid treatment, implying thai these roots had undergone changes that reduced the effects of a demineralizing agent. •o HANES P. O'BRIEN N, GAJINICK J: A morphologic compar- •• ison of radicular dentin following root planing and treatment wuh Citric acid or tetracvcline HCL / Clin Penodonioi 1991, 18:t*CM)68. \n evaluation usinj{ scanning electron microscopy is presented of the morphology of dentin after the use of hand instruments, citnc acid (pH-l. J mint, and tetracvcline (pH-3 2, 5 mint. Hand instruments produced a smear layer, with no dentinal orifices exposed Citric jciti produced round-to-ova! dentinal orifices shat were irregular in shape, flared, or funneled in appearance Tetracvcline produced numerous liennnal orifices thai were variable in size and *.iune. with some specimens exhibiting a layer of organic debris. to LEBAHN R. FAHRENBACH W, CLARK 5, UE T, ADAMS D Root • dentin morphology after different modes of citric acid and tetraevchne hvdrochloride conditioning. J PvntxU>ntt>i 1902. 63:303-309 Twenty denun blocks trom Ireshlv extneted. nondtseased human molars were rtxil-pianed and treated wuh citnc acid or tetracvcline for 30. 00. 120. and 2-*0 seconds There was a time dependent increase in dentinal lubule diameter wuh citnc acid. Citnc acid caused more extensive changes than letracycline 47. STERRET J, DELANEY B. RIZICALLA A. HAWKINS C Optimal citric acid concentration for deminal derruneralization. Quintessence Int 1991. 22.371-375 -iH CHAVES E. COX C, MORRISON E, CAFFESSE R. The effect of •• citric acid application on penodonully involved root surfaces. I. An in film light microscopic study, Int I Penodonl Rest Dent 1992. 12:219-229. Forty penodontally involved teeth were divided into four groups: no treatment, citric acid treatment, nxx planing, and citnc acid with n.Kjt planing Ciim Ji id application .mine had no effect on the root surface and did not alter the appearance or penetrate the dentinal tubules of the planed root surface. The authors noted an incomplete removal of the cementum without careful root planing in an in iitro model. The effects obtained after scaling and root planing were not altered bv curie acid application on a light microscopic level, 49. WIKESIO U. CLAFFEY N. NHVEUS R. EGELBERG I PenodontaJ repair in dogs: effect of root surface treatment with stannous flouride or citnc acid" on root resorption. / Penodomol 1991. 62 180-184. 50. AUKHIL 1. PETTF.RSSON E: Effect of citric acid conditioning on rtbroblast cell densitv m penodontal wounds. J Clin Penodontoi 198*. I4:80-*4. 51. PETTERSSON E, ALKHIL i. Citric acid conditioning of roots affects guided tissue regeneration in experimental penodontaJ wounds. J Penodonl Res I9H0 21 543-552. 52. BOWERS GM. REDDI AH: Regenerating the penodontium •• in advanced penodonul disease. / Am Dent Assoc 1992. 122:45-48. An excellent review of some current approaches and future directions for penodontal regeneration. The authors reference his- [ologic research, documenting regeneration using autologous cantellous bone and marrow References ure cued for use of DFDBA materials with the limiting factor being limited performance in supracrestal (and furcation) defects due to the small particle size allowing displacement by overlvmg flap The authors discuss the fear of disease transmission and quote from the literature estimating the risk of transmuting HIV as being one m 8 million after the graft material is frozen and with proper tissue banking. The authors also provided a detailed explanation of the nme-relaled cellular and molecular events in the bone-induction process. Future techniques and materials are mentioned and include the use of morphogenic protesns produced by recombmant DNA techniques One such bone-induilive protein, osteogenin. in association with a bone-denved collagenous matrix, appears (O be safe in humans and is cun-ently being evaluated. 53. FROUM Sj, THALER R. S<:OPP IW. STAHL VV Osseous autografts. II Histological responses to osseous coagulumbonc blend grafts / Penodontoi 1976. 46<:iM>-<>o! 54. SCHALLHOR-N R<, Present status of osseous grafting procedures. I Penodontoi 19T 48:5-()-S~() 55. HlATT W"H. SCHALLHORM KG. AAKONIAN A| The induction of new bone and cementum formation IN' Microscopic examination ot the penodontium following human bone and marrow allogrart. autograft and nongrart penodonul regenerative procedures / Periadoniol 1978. 4<M95-M2 Periodontal regeneration Froum and Comez 123 50 Bovrem GM. 5CKAUHORN RG. MELLONIG IT. Histologic evaluation of new attachment in human intrabony defects: A literature review / Penodontol 1982. 53:509-514. greater for sues treaied with the implant material From vears 2 to •+. Rains in probing attachment improved with the hvdroxvapautetreated sites but deteriorated in the control sites. MFLLOMG [T. Freeze-dried bone allografts in periodontal reconstructive surgery [X'tital dimes of Sorth America 1991. 35:505-520, ^H MELIDNIG IT. PREWETT AH. MOVER MP HIV inactivation in •• a bone allograft / Periodontoi 1992. 63:979-^983. Direct evidence is presented demonstrating that processing of a DFDBA renders the allogrart safe tor human use. Using diseasetree tomcat bone that was then contaminated with viral particles, .ind conical bone from a donor who died of AJDS. the authors -.how ih.ii all treaied samples were negative when assaved for HIV. 59 BOWERS G. FELTON F. MIDDLETON C. GVLNN D, SHARP S, • • MELLONIG J. GORIO R. EMERSON I. PARK S. SUZUKI J. MA S, ROMBERC E. REDD: AH: Histological comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone aUograft and with puniied bone collagen. / Penodonloi 1991, 62:690-702. Ising the calculus noich marking system, the authors histologically t-vaiualed Mi submerged defects in eight patients and 50 nonsubmerged defects in six patients wiih omonth biopsies The findings indicate thai osteogemn combined with DFDBA enhanced regeneration in a submerged environment In nonsubmerged defects DFDBA and osteofjenin and DFDBA alone formed significantly more new attachment than either tendon-Jenved mamx plus osleogenin or tendon-derived matrix alone. Also, osteogenin did nol impair normal lymphocyte blastogenesis 0 months postsurgery. (i0 DRIRY Gl. YIKNA RA: Histolopic evaluation of combining • tetracycline and allogenic frccze-dried bone on bone regeneration in experimented defects in baboons / Penodonloi 1991. 62,052-658 The authors used nylon mesh chambers placed in surgically erejtted windows in the mandible of hatxxms to determine it tetrancline rehydration of FDBA would enhance txme regeneration mmpared with rehydration of KDBA with stenle water. Three- ,ind five-week histology demonstrated much greater (>5 xt new bone formation with letracycline rehvdraied compared with the water-rehvdrated FDBA ol ISAKSSON S. AJLBEKIUS P: Companson of regenerative capac- • itv elicited by demineralized bone matrix of different embnonic ongins. / (.ramomaxillofuc Siin^ 1992, 20:73-80. The osieoinduction capacity of demineralized bone matrix was i nnnrmed Fitteen-week results with demir.eralized bone matrix (of Ixnh membranous and t-nchondral origin I implanted in trephined calvaral delects in adult rabbits displayed extensive osteomduclive ijpacirv and early bone production lhal signincantlv exceeded the ivvo controls, autogenous btine chips and an unfilled detect '.ID, MELLONIG .IT. GRAY [L. TONXIE HI: Companson of freeze-dried bone aliograft and porous hydroxvlapatite in human periodontoi defects. / Penodottlol 19H9. 60:231-2.17 63 GAICLT PN. WMTF IM. BR(XJKSHA« |D, KINGSTON CP; A • t-vear controlled clinical study into the use of a ceramic hydroxylapaiitr implant matenal tor the treatment ot pen- (Kiontal bone defects. / Out PeniKlunloi 1992, 19 5"O-5 The authors reported on -t-vear clinical results comparing 58 sites treated with nonresorhjble hvdroxvapatittr and 5') sues treated hy OFI). Pockeis were taiegonzed as shallow (less than 3 mm), moderate ( j mm to o mm i and deep I greater than o mm). Both lesl and control groups !t>st attachment (0» mm and I ,i» mm I in shallow ^Hts For moderate and deep ptx.kels. IHMII groups gained aitachnicnt At the -tth year, reduction in pocket depth i\us significantly 04 MELLONIG JT: Porous paniculate hvdroxyapatite in a human • periodontal osseous defect: a case report. Int j Penodonl Res: Dent 1991, 11:217-223. A tooth diagnosed as peiiodontally hopeless was treated wiih a synthetic bone graft (porous hvdroxyapatite) and was extracted 1 vear postsurgery. Clinical findings indicated a fractured root. Histologic examination revealed previously planed fibrous connective tissue attached to the rool surface. This connective tissue contained particles of hydroxyapatite. Because the author did not delineate the extent of root planing, a determination of new attachment or reattachment cannol be made. 65. STAHL S. FROL'M S: Histologjc and clinical responses to porous hydroxyapatite implants in human penodontal defects three to twelve months post-implantation. / Penodontol 1987. 58:689-695. 66. FRANK RM, KLEUPANSKY P. HEMMERLE j , TENENBALM H ukra- •• structural demonstration of the importance of crystal size of bioceramic powders implanted into human penodoncaJ lesions. J Clm Penodomol 1991. 18669-680. The authors reported on bone formation following implantation of three bioceramic powders into human penodontal lesions Twelve-month biopsies of sues implanted with B tricalcium phosphate or hydroxyapatite were compared wiih 6-month biopsies ot sites implanted with microsized hydroxyapatite The authors concluded that bone formation around the three bioceramics occurred through similar mechanisms at the ultrastructural ievel. However. by 6 months, small microsized hydroxvapatite had a significantly greater amount of peripheral bone compared with the other ceramics at 12 months. The authors concluded that crystal size may be important in determining the efficiency of bone formation They recommend that the manufacturer indicate the crystal size of the various bioceramic powders 67. ZANER DJ. YUKNA RA: Particle size of penodontal bone grafting materials. ./ Perttxioiiloi 1984. SS 406—+09. <>8. WILSON J. Low SB. Bioactive ceramics for penodontal treat- • ment: comparative studies in patus monkey / Appl BUimat 1992, 3:123-129. The authors compared four bioactive ceramic materials. Two forms of Bioglass: synihagraft and augmen. and alveolograf and penogral were implanted in surgically created defects in o adult monkeys (Hrythrocebus patus) All four ceramics allowed bone repair but Hioglass appeared to limit the downgrowth ot epithelium. The authors claim that bone growth from the surface of the alveolus is augmented by bone growth on the Bioglass surface, thus causing a more rapid fill of the defect with Bioglass. (>9. SHAMIRI S. SINGH IJ, STAHL SS Clinical response to the use • of HTR polymer implant in human intrabony lesions. Int J Penodont Rest Dent IW2. 23:295-299 This siudy compared hard-tissue replacement polymer versus OFD in 30 intrabony defects in 15 patients. Their findings demonstrated that whereas pocket reduction was significantly greater initially in the control sues, there was no significant difference in pixket reduction responses JI 12 months postsurgery. "0. STAHL .SS. Fnot M M. T\KSOU I) Human clinical and histolugical responses to the placement of HTR polymer particles in intrabony lesions. / Periadotitoi W90. G1.2G9-2~-i "1. MELCHEB AH: On repair potential of penodontal tissues. / PenuUontoI !*>"(). 4~ 25C)-2tK) 124 Periodontology MELCHER AH1. CHEONO T. COX J. NEMETH E. SHIGA A: Synthesis of cement um-likc and bone-like tissue in vitro may migrate into the pcnodontal ligament in vivo. / Penodont Res 1986. >l 592-612. MHCHEP AH McCt LLOCH C: Cells from bone synthesize cementum-likc and bone-like tissue in vitro and may rrukiratc into pcriodontai ligament in vivo. / Pertodont Res HI NYMAN S: Bone regeneration using the principle of guided •• tissue regeneration, j Clm Penodontol 1991 I8:-^)H—(48 Reviewed the history of GTR and discussed the use of membranes m endodontic surgerv, ndge augmentation, and implants. 82. POSTLEWAITE A. SEYER J. K.\.NG A Clhcmoucuc attraction of human hhrohlasts to npe 1. II. Ill collageiu and collagen derived peptides. Proc Sail Mad 5<ri U S A 1978. ~-i VYMAN S GoTTtow I. KARRINC'F T The regenerative poteniial of pcnodomal ligament: an experimental study in the monkey. / Ctin Pvnodontol 1982. 9:257-265. "5 SYMAN S. UNDHE J. KARJUNC T: New atiachment following surgical treatment of penodontal disease. J Ctin Penodonlol 19H2. 9 290-2'Hi •'6. IXFF H Guided tissue regeneration: a new frontier in pe- • ruxiomics. / Vub fh'ni Assoc l'Wl. Apr/May: 1 T - 19 In ihi.s literature review, ihe author notes that the use of mernhranes in GTR is best m three wall intrabony lesions, and class II furca with vertical bone loss. He pomis out that careful case selection is crucial, and that the surgical technique is demanding He Mates that the exact nature of attachment with OTR in humans is not completely elucidated DOWH1 P. Mi IRAN .1, QLTEISH D Guided tissue regenera- • lion. Br Dent ! 1991, 171:125-12"-. The authors discussed the materials used in GTR. and their limitations Oore-Tex has a tendency to adhere to root surfaces during healing, preventing cell regeneration in the area (it contact- It is expensive, and recession is u common sequel. Miilipore fillers are brittle and difficult to manipulate. Collagen membranes do not consistently provide new attachment in humans. There is the risk of developing Creutzfeldt-Jakob disease if dura mater is used. Poiylactic acid has not been sufficiently studied. "H I'HILLIPS I I'ALUV M: A review (it the guided tissue regen- • eration concept Gen Dent 1W2. Mar/Apr: 118-123 The authors reviewed the various materials used in GTR and pointed out the problems in using nonresorbable membranes. These problems include abscess formation, membrane exfoliation, jnd recession They also pointed out the varierv of responses and the lack tit long-term predictability and Mobility of GTR-lreateti defects "9 CAFFESSE K. BECKED »' Principles and techniques of guided •• nssue regeneration. Dent din Sorth Am 1991. J5:479-*94 A review ot the literature is presented. The authors point out that ihe ideal defects for GTR procedures are three-wall defects, two- In three-wall defects funnel-shaped detects with definite osseous Mops greater than S mm deep, and class it furca with or without a vertical component Kull thickness ilaps are used in the surj;]- <.al procedure The interdental papillae are retained, and vertical a incisions are recommended MI) MlNABE M A critical review <>t the biologic rationale for • • guided tissue regeneration. / Periotiontoi 1991. 62:171-179. This is .i uood literature review' wuh u tabulation irf results from .inimal jnd human studies. The author pointed nut that detects lievond a tertain size may not be compleie.lv restored bv GTR. .ind the morphology ot the detect as well as postsuriycal recession .ire importam m the success of GTR. The author also pointed out uie advantage nt Cl'Fs to decrease recession VChen discussing re- •Jirbahle membranes, the author noted that the time ol degradauon <•! ihe membrane is crucial, but the critical period for nl the resorbahie membrane is still noi known 8^. COOPERMAN L. MICHAEU D The immunogemcity of inlectable collagen I: A one year prospective study / Amer Acad Dermatoi 1984. 10:<)3H-o-t<> 84. FLANARY D, TWOHEY S. GRAY J, MELLOMG J. GHER M The • use of synthetic skin substitute is a physical barrier to enhance healing in human penodontal furcation defects: a follow up report. / Penodontol 1991. 62:68+^89. The authors evaluated the use of Biobrane. a synthetic skin substitute of polydimethylsiloxane bonded to nvion tabnc with peptides from porcine dermal collagens. In paired class II furcation defects in mandibuiar molars in humans, none of the furca treated with the material were completely closed in a horizontal direction at the b-momh reentry point. The authors concluded that Hiobranthas limited clinical application in GTR H";. GALGIT R. PrntOLA K. WAITF I, DOYU I. SMITH R Histologic • evaluation of biodegradable membranes placed transcuta neousty in rats. / CUn Penodontol 1991. 18 SH1-SH6. The authors evaluated the hisiologic responses to Miilipore, Gore- Tex, and two biodegradable materials of different molecular weights in iranscutaneous wounds in rats. Healing was governed by a variety of factors, including host responses, the chemical composition of the materials, the physical and surface character of the material, its porosiry. and the depth of insertion into the tissue. Kf) QLTEISH D. DOLBY AE: The use of irradiated crosvlinked • human collagen membrane in guided tissue regeneration. / Clm Periodontol 1992, 19 H ' < > - ^ Type I collagen was extracted, prepared, irradiated, and crosslinked. The collagen was placed in 2() penodontal detects in 19 patients. No untoward reactions were observed in the test period There was no reentry. Clinical examination revealed a yam ol jltachmenl with the use of this collagen preparation. 87. I'AL'L B. MFLLONIC I. TO*I.R H. GHAS. I Lse of collagen • barrier to enhance healing in human penodontal furcation defects, int j Periottonl (test Dent IW. 12:123-131. The authors used (ollisu; in paired class 11 furcation defects in seven patients. The studv reported an improvement in probing depths and horizontal osseous support with Colhstat. but the changes adjacent to the matenal mav have been due lo difference in defect morphology rather than to a function of the barrier. 88. WARRER K, KAKKIM. T The effect ot Tissecl on healing • after penodontal flap surgerv. / f.7i« Pi>nodimi<tt IW2. Tisseel. a two-component adhesive system with lihronectin. was used in s-mm defects in four dogs. The animals were sacrificed in 4 months. Ti.sseel failed to facilitate repopulation ot the rool surface wuh pcnodomal ligament cells on a predictable basis Tissed ntay not lavor new attachmenl unless the rool is |irt-trealed with ulnc .icid S') TAL H. I'liAHt i Rirmation ill new penodontal attachment • apparatus after experimental root isolation with collagen membranes in the dog. hit I I'rnmiinu Rest Dent I'J1^. 12:231-242. Periodontal regeneration Froum and Gomez 125 Four-mm buccai defects were induced in maxillarv canines, and l-shaped defects were induced in premolars ol nine dogs. Mem- Cranes made of collagen from rai tail were plated Animals were sacrificed at tu jnd 50 days Histology showed lunctional epithelium ot the coronal ^uaner ot the delect, wuh new bone, penodontal ligament, and cementum at (he apical half, Connective- Lissue adhesion was seen between [he functional epithelium and new cementum No bone tnrmation was seen in the canines. 90 l.KKOMi: V. KENNTV B. ( AAKANZA F. MAKTKNONI M: The use • of autogenous periosicaJ grafts as barriers tor the treatment of class II furcations involvements in lower molars. I /V rnxtowot 1991. 61:77V-780. Fifteen patients with class II furcation defects were treated using periosteum as a hamer to utilize progenitor cells in the periosteum The sues were reentered in 6 months. The use of penosleum vielded similar results to those reported in the Gore-Tex siudies. The periosteum may modify the cellular dynamics ol wound healing. 91 YlKNA K CUnical human comparison of expanded polyte- • lrafluoreihvlcne tamer membrane and freeze dried dura mater allograrts lor guided tissue regeneration of lost peruxlontai support. I. MandibuUr molar class II furcations. / Penndoniul 1992. 6M31-*-t2- Yukna compared Gure-Tex and freeze-dried dura mater in the ireatment of class II furcation defects in mandibular molars in humans, with a 12-month reentry evaluation He saw no "complete* fill in furcations with soft- or reformed tissue, leading him to question the use ol GTR in the management of class It furcation defects. 92. KON S, Ri BEN ML BLOOM A. DEY tt'M. BOFFA J: Regenera- •• tion of penodonial ligament using resorbable and non-resorbable membranes clinical. histoJogicaJ and histometric study in do^s. hit I Periodont Resl [X'ril 1991. 11:59-71. Defects measuring 5 mm by <i mm were created in three dogs and were treated with Victyl, Gore-Tex and control sites, Gore- Tex was removed in 5 weeks New attachment divided inio ihree /.ones: apical zone had penodontal ligament, bone, and cementum. Middle zone had hbers into cementum and cementoid. The coronal /.one had loose connective nssue in an undefined structure. Vicryl had I -trt mm of regeneranon ^ixrv percent of the lesion (0-9 mm) h.id new attachment apicailv. -tl)% 10.^8 mnu had connective nssue attachment inserted in cementoid tor undefined structure* coronal to (he Nine. 91 METZLER 1). SKAMONS B. MEIXONIC J. GHER M. GRAY J: Clin- •• ical evaluation of guided tissue regeneration in the treatment of maxillarv class It molar furcation invasions. / Penottontot 1991. 62:355-560. Seventeen pauenis with paired class II furcation problems on maxillary molars were treated with OFD or placement of Gore-Tex membrane Membranes were removed in •> weeks, and sites were reentered at <> months Recession was setrn in 50% of the cases. No defect rilled" with bone in o months There was an increase in attachment levels and a decrease in probing depths, but regeneration was not predictable The authors suggested the use of citric acid. letracvciine or allograrts to enhance results ligament was seen where new bone and cemenium formed Part II involved through-and-through furcation defects ij mm high. 4 mm wide) treated with Gore-Tex. Animals were sacrificed at -n Jays. Histology' showed new collagen in one ot five test sues. The remaining sues had partial healing with new attachment. Lick of new attachment was correlated to tlap recession and membrane exposure 2 weeks alter the surgery. Part [II involved creating wide, ihrough-and-lhrough defects (S mm high, -t mm wide) Gore-Tex was placed, jnd animals were sacrificed in -ti days There was recession in all the teeth, and no new cementum in eight ol ihe 10 furcations studied. Guided tissue regeneration mav result in new attachment in furcation defects, but the size of the defect and the degree of bone loss ad|acent to the defect and the soft-tissue recession determines ihe outcome of regenerative procedures. l>v CATON J, WAGENER C, POLSON A. NYMAN S, FRANTZ B. •• BOI'WSMA O, BUEDEN T: Guided tissue regeneration in intcrproximal defects in monkeys Int J Penodom Rest Dent 1992. 12:267-2" One-wall interproximal defects were created in monkevs. and Gore-Tex was placed. The membranes were left for 1 and 3 months, at which times the animals were sacrificed. At 1 month, there was (unctional epithelium to the membrane, new cementum. cementoblast-like cells in the apical area, immature penodonial ligament, new bone, and osteoid. At 3 months, there was mature cemenium with Sharpey s fibers in the coronal one third of the root, and new bone. Some of the angular defects filled completely with bone, maintaining a penodonia! ligament space. The new penodontal ligumeni had normal morphology The position of the barrier denned the magnitude of coronal regeneration Fhe authors suggested leaving barriers in place tor longer periods of time—anywhere Irom I to j months %. Li: I Topographical characteristics of root trunk lengths • related to guided tissue regeneranon. / Penodonial 1992. 63:215-216 Lu studied the topography of root trunks and found that LM°<) ill the molars studied had concavity depths on the trunks that prevented (he membranes from adapting to the root. The author •-uKgested a supragingital placemen! ot the membrane to avoid ibis concavity. 97. WF.NZEL A. WARKKR K. K.AKR1NI. T Digital subtraction radio- • graphy in assessing bone changes in penodontal defects following guided tissue regeneration. I Ctin Penmiunlol 1992. 19:208-213 Clinical gain of attachment is accompanied by formation of new alveolar bone. The amount of Ixme formation alter GTR vanes considerably. Changes in the marginal bone level determined by conventional radiography are terminated in o months Bone changes after GTR correlated better with clinical measurements of attachment gain when assessed with digital subtraction radiography. 98. BRAGUER U. HAMMERLE CHF. MOMBEIU A, BlRGlN W. LANO • NP: Remodelling of periodonul tissues adjacent to sites treated according to the principles of guided tissue regeneration. / Ciin Pvnodontoi 1992. 19:G1S-G2-+. The authors noted that because hard-tissue changes are complete in 1 vear, reentry should not he done unul that time 94 PONTOHHtO K. NYMAN Y ERICSSON I. LlNliHE I Guided tis- •• sue regeneration in surgically produced furcation defects, an experimental studv in the beagle dog. / Clin Pentxionlot 1992. 19 IW-163 Han I ot the studv involved creating "keyhole" defects (I x 1 mm) in the furcations ol dogs. Gore-Tex was placed and removed in M) davs, and animals were sacrificed at -t months. Histology revealed new cementum and collagen in ihe roots lacing the furcation detect. Bone regeneration ot 0.99 to 2 3 mm was .seen (i0% to 100% ot original bone height restored). Kunctior.allv oriented penodoniai 99. GOTTLOW I. NYMAN S. KAHJUNO I" Maintenance of new • attachment gained through guided tissue regeneration. / Clin Penodontol 1992. 19:315-317 Gain of probing attachment was observed in HO new attachment •.ues: 80 were monitored for 1 year. t>7 for 2 vears. -vi tor 3 \eare. 1" for -4 years, and nine for S vears Nine ot nine sites at i vears were found to have retained the improved probing attachment level value. The gain of probing atiachmem observed mav reflect a new connective tissue attachmcni that can be maintained on a long-term basis. 126 Periodontology S00. C.HEVSTAD HJ, LEKNF-S KN: Ultrastniciurc of PTFE membrane associated plaque. / Dent Res 1992. "2 -580. 101 KARJUNG T: Clinical results of guided tissue regeneration: what are its limitations? J Dent Res 1992. "2 519 102 GOMEZ C. LlNKE H Microbiota around the Gore-Tex periodontal matenaJ. I Dent Res 1992. 7t:2i6. 10.V MARTIN M. G ANTES B GARRETT S. F.CELBERC; |: Treatment of periiRlonul furcation defects. I. Review of literature and description of regenerative surgical technique. J Clin Penodontol 1988, IS 227-231. 104. GOTTLOW J N'YMAN S. KARRING T. LJNDHE J: Treatment of localized Ringival recessions with corotuUy displaced flaps and citnc acid: an experimental study in the dog. J Clin Penodontoi 1986. 13:57-63. 105. NILVEUS R, JOHANNESSON D. EGEUiERC J: The effects of autogenous cancriicius bone grafts on healing of experimental defects in dogs. / Periodonl Res 1978, 13-532-537, )06. CIANTES 8, MARTIN M, GARJIETT S. EGELBERG J: Treatment of pehodonul furcation defects. II. [tone regeneration of mandibular class II defects. / Clin PenoUonloi 1988, 15:232-239 107. CRJGGER M. BOGU G. NILVEUS R. EGELBERG J. SELVIG K: The effect of topical citnc acid application to the healing response of experimental furcation defects in dogs. J Penodont Ra 1978, l3:53&-">42. 108. BOGLE G, CLAFFEY N. FGELBERG J Healing of horizontal circumferential periodontal defects following regenerative surgery in beagle dogs. / Clin Periodontol 1985, 12:837-849 109 ('.ANTES M. SYMOWSKY B. GARHETT S. F.GELBERG J: Treat- • ment of pcnodontal furcation defects: ManUihular class III defects. / Penodontoi 1991. 62361-365. Twenty-seven class III furcation defects in mandibular molars were treated by citnc acid root conditioning and CPF (in CPF 14 cast's, otnc acid, and DKI)BA in 13 fuses). Clinical measurements were taken and reevaluated b months after treatment Vertical probing depth-reduction and mean probing aitachment-level gain in (he furca were 2.6 mm and 2.2 mm for ihe nongrafted defects and 19 mm and 1.5 mm for the grafted defects. No differences were observed between ihe defects trealed with or without bone grafts. 110. GANTES B, GARRETT S: Cororolly displaced flaps in recon- •• sirucuve penodontaj therapy. Dent Clin North Am 1991. 35:495-504. This paper was a presentation of studies performed on dogs and humans. The first part was a hislologic documentation of healing responses in dogs lo CPF and citnc acid (pH-1. 3 min) Small furcation defects were successfully regenerated, but large defects had no pnmarv closure and were not treated with success. Citric acid with extreme CPFs (clinical crowns completely covered) showed complete regeneration, with flaps gniduallv receding and stabilizing at the cemenioenamel lunction Citric acid with moderate coronal position (Haps anchored 1 mm above the cementoenamel lunction. sutures attached to enamel with composite) showed that if the flaps staved attached to the crowns, regeneration occurred. Clinical techniques and flap design tor use in clinical situations were presented. The authors also reported on the treatment of class II furcation problems using citric acid and CPF Only 50% of ihe lesions were paruallv closed, while 4H% completely closed. I'rohmg depths were reduced from 5.5 mm to 2 mm Decreases in probing depth were due to gain in attachment, not recession. I l l SCHALLHORN KG. McCuiN PK Combined osseous composite grafting, root conditioning and guided tissue regeneration. Int J Penodont Rest Dent 1988. 8 9-31 112. HANDELSMAN M. DAVARPANAH M. CELEETI R: Guided tissue •• regeneration with and without citric acid treatment in vertical osseous defects. int J Penodont Rest Dent 1991. 11:351-363. The authors compared the use of a PTFE membrane in the treat ment of intraosseous defects with and without prior root conditioning wiih citnc acid (pH"l lor 3 minutest. Although in both groups clinical parameters were improved, there were no statistically significant differences between the two groups Citric acid root conditioning did not enhance clinical findings when compared to the membrane-only group. 113 ANDEREGG CR. MARTIN SJ, GRAY JL. MELLOMG JT, GHER •• ME: Clinical evaluation of the use of decalcified freezedried bone allograft with guided tissue regeneration in the treatment oi molar furcation invasions, j Penodontoi 1991. 62:26+-268. The authors compared the use of membrane barrier aione (PTFE> or in combination with DFDBA in (he treatment of class II and ill furcation invasions. Six months post-treatment, surgical reentry on each site <27 class II and three class 111 furcations) showed no dttlerence in attachment level changes bul greater reduction of probsng depths in the sues treated with DFDBA and membrane versus membrane alone Although hard-tissue changes were comparable for alveolar crest resorption. there was a statistically greater horizontal and vertical bone repair in defects treated with the DFDBA and membrane combination. However the authors note that onlyfour sites of 30 completely closed. 114. FATH S. WACHTEL HC, BERMMOILIN JP Treatment of periodontal intrabony lesions with the GTR technique and hydroxylapatite implants. / Dent Res IW2. "2(special is- .sue):624. 115. YAMAHA S. TAKAHASHI V. VAMANOICHI K: Penodontal healing following guided tissue regeneration with bone matrix application. / Dent Res 1992, 72<special issuetiBl 116. WARREN K. KAKRING T Guided tissue regeneration com- • bined with osseous grafting in suprabonv penodontal lesions. J Clin Penixiontoi 1992. 19:J?3-3H0 Surgically created horizontal defects in three dogs compared the use of a Teflon membrane (Zitex) with a fibrin sealant (Tisseel) with the membrane, sealant, and Kielbone. Various complications and exposure of the membrane occurred during the study phase Hisiologic analvsis after 3 to i months of healing failed to demonstrate consistent penodontal regeneration in either of the two groups. The authors caution against the use of large membranes that may result in rxxir wound closure and disturbed healing, leading to a loss of the grafted materials. 117. STAHL bS. FROUM S: Human imrabony lesion responses to •• debridement. porous hydroxylapalite implants and teflon barrier membranes. / Clin Penodanlol 1992. 18605-610 A Teflon membrane and porous hydroxyapaiue were used in the treatment of seven vertical lesions at seven teeth in three adults. Notches were placed in calculus and hlocks were taken H> to 28 weeks postsurgery Hislologically. two sites exhibned closure by long |unctional epithelium. The remaining live sues showed gingival recession to be apical to the calculus notch tor epithelium in the notch). However, cellular cememum was seen lust apical to the notch Within the osseous crater, increased bone mass, and functionally orienied penodontal ligament was seen 118. STAHL SS. FROUM SJ: Healing of human suprabonv lesions treated with guided tissue regeneration and coroPeriodontal regeneration Froum and Comez 127 rally anchored flaps: case reports. / Cltn Penodomol 1991. 18 69-74. 119 STAHL SS. FROUM S: Human suprabony healing responses • • following root demmeralization and coronal flap anchorage: histologic responses in 7 sites. / Clin Periodontol 1991, Seven suprabony lesions on anlenor teeth of two panenis were treated with root debndement and citric acid conditioning Flaps were coronally positioned or coronally anchored to orthodontic brackets bonded to enamel Block sections were taken at 7 and 18 weeks after surgery The average gam of attachment was 1,8 mm in CPF. and -t.i mm with coronal anchorage Coronally anchored sites had new attachment in all instances. One site gained ft.7 mm in 18 weeks New cellular cementum was present, with attached fibers on dentin. There were varying degrees of crestal osteogenests in all specimens. 120 WIKESIO UME. BOOLE GC, NILVEUS RE: Periodontal repair • • in dogs; effect of a composite graft protocol on healing in supra alveolar periodonul defei.is. / Penodonloi 1992, 63107-113. The studv evaluated a composite graft protocol for treating surgically created supra-alveolar penodontal defects in beagle dogs. A comparison was made between a test group treated with citric acid and tetracycline root conditioning followed hv placement of a lomposiie graft (including hydroxvapanie. FDBA. tetracycline and hbronectin* and flaps sutured to cover most of the crowns of the teeth and a control group of citric acid root conditioning and similarly positioned flaps. Connective-tissue repair was greater in the control group (98% vs 60% of defect height! compared wnh the composite graft group Rooi resorpcton was observed on almost all teeth wnh ankylosis present on two ciiric-acid-ireaied teeth. The composite graft pro«xol did not offer anv advantages over cilnc acid conditioning alone as an adjunct to CPFs in this model system 121 VCANG HL. SOMKRMAN Ml: Periodontal connective tissue. • • Curr qpiM Dent 1991. 1.HI&-H2S. The review summarizes current information on proteins and factors associated with the periodoniium. li also references literature on >>rowth factors associated with penodonul tissue regeneration. 122 RJPAMONTI U, REOOI AH (irowth and morphogcnetic fac- • tors in hone induction: role of osicogenin and related bone morphogenetic proteins in craruofacial and pcnodonlal bone repair. Crtt Ret) Oral Bioi Med 1992, 3 1-1-t The developmental cascade for collagenous matrix-bone formation, including migration of progenitor cells by chemoiaxis. attachment of cells through nhronectin. proliferation of mesenchymal cells, and ditterenliation of bone is discussed The bone-inductive protem oMeogenin. its denvation as recombinant osteogenin. and applications to oral and orthopedic surgery are presented. 123 1-IYTEN HP. V( MY. YANAGISHfTA M. VlKICEVIC. S. HAMMONDS KG KUJDI Ail Natural bovine osteogerun and rccombinani human bone morphogeneiic Pmtein-2B are cquipoient in the maintenance ot proteoglycans in bovine articular cartilage explant cultures. } Biot Cbem 1992, 267 •««1-V)')S 124 I.YNi.H SE, DECASTIUA (jR. VX'tt.UAAfS KC. KlBITSV CP, IIOWELl. • • TH. RKI)[>V MS, ANTONIAUGS HN The effects of shon-ierm application of a combination of platelet-derived and insulinlike growth factors on penodontal wound healing. / Pen nduntol 1991, 62/I^H-167 This studv on beagie dugs contrasted J lea group utilizing a combination of recombinant platelet derived growth tactor-H and insulin-like growth (actor I. in a methvkelluiose gel. with a control eroup receiving the gel alone Two and T weeks postsurgerv revealed a significant I five to I0-fold> increase in new bone and cementum in the test sites compared with the control gel A physiologic ligament space was formed berween the new bone and cementum and no increase in ankylosis was seen ai the lest sites. 125. RLrrHERFORO RH, N1EKRA.SH CE. KENNEDY JE. CHARETTE MF: • • Platelet-derived and insulin-like growth factors stimulate regeneration of penodontal attachment in monkeys. J Penodonl Res 1992. 27:28V290 The regimen of platelet-denved and insulin-like growth factors induced regeneration ol nearly ^(M of lost attachment in -i weeks in ligature-induced defects in adull monkeys New attachment in some cases included regeneration of horizontally resorbed interdental septa. 126. MATSUDA N. KUMAR W-L NM. CHO MI, GENCO RJ: Mitogemc, • chemotactic. and synthetic responses of rat penodonul Ligament hbroblastic cells to polypepude growth factors in vitro. J Penodontoi 1992, 63:51<t-'i25. Using penodomal ligament cells obumed from the coagulum of healing tooth sockets in rats, epidermal growth faaor. transforming growth factor (J. recombinant human plalelet-denved growth factor rh, platelet-denved growth faaor pp. natural platelet-derived growth factor a p. and insulin-like growth factor-1 were examined in intro. Transforming growth faaor p revealed no and epidermal growth factor slightly increased chemotactic effects. Both rh platelet-derived growth faaor-a(J and transforming growth faaor (i stimulated collagen svnthesis Insulin-like growth faaor-1 had no erlect on collagen synthesis. Findings suggest that rh platelet-derived growth faaor p"P and insulin-like growth factor-1 stimulate mitogenesis proliferation and chemoiaxis ol penodontal ligament fibroblastic cells and may thus be useful for clinical application in penodontal regenerative procedures. 127. TAKESHITA A, ZMON GYINC; NJU HANAZATA S. TAKARA I. HIGUCHI H, KAFAYAMA I. KITANO S Effect of interleukin- If3 on gene expressions and functions of fibroblastic cells derived from human penodontal ligament. / Penoetont Res 1992. 27:2<; 128. RIPAMONTI U, MA SS. RKDO] AH: Induction of bone in com- • posites of osteogenin and porous hvdroxvapatite in haboons. /'last Rixonstr Sum 1992. 89:731-7^9 This study examined the osteogenic potential of osteogemn in combination wnh porous nonresorbable and resorbable hydroxyapatiie. Rods impregnated wnh osieogenin were implanted intramuscularly in eight adult baboons. Specimens at 30 and 90 days showed no evidence of bone in the resorbable hvdroxvapatite with and without osteogemn. The nonresorbabie hvdroxyapatite showed evidence of bone independent of the osteogemn Osteogemn did not increase significantly the amount of bone formation. 129. YKWEY GL. TllTON Aj, SOMEHMAN Ml. Dl'NN RL Delivery • of periodontal tissue-regeneration factors. / Dent Kes 1992. 7l(special issuei:29HFibronectin and Rbrohlasi growth factor were incorporated in a biodegradable polymer (Atngelf I>I tttm to test the ethcacv ot this as a delivery system The bioactiviry of fibronectin released was measured by in Vitro penodontal ligament cell attachment jnd recorded 4S% 10 9-t'"o of native hlironectm bioacnvirv Released fibroblasi growth factor gave a bioactiviry ot H3°* to 100% 130 WIKFSJO 11MF.. NlLVEtis RE. SELVKi KA: Signihcance of eartv • • healing events on periodontal repair: a review. / Penodonlol 1992. 63 ISH-loS The authors review healing sludies and conclude thai connectivenssue repair to the root surface (ollnwmg reconstructive penodontal surgery is a function ol the establishment and maintenance ot a liable root surface adhering fibrin clot. Tins clot will prevent apical 128 Periodontology migration of gingival epithelium and allow for new connective-tis- |unctional epithelium with l>5% of the occlusai-apical length of the sue attachment without ankvlosis or Ions |unclional epithelium. defects repopulated by connective-tissue cells in the enriched collagen group. In the iron enriched bilavered collagen barrier und 131. HITWUJ S, NOFF M, GROSSKOPF A. ROSES O, TAL H. SARION mono-layered nonennched collagen barrier group, a lung |unc- •• V Hcparan sulfate ind tibroncctin improve the capacity of Monal epithelium developed, wiih only 65% of defea being recollagen barriers to prevent apical migration of the junc- populated by connective-tissue ceils. tional epithelium / Penodomot l')91. 62:S98-hOl liilayered collagen barriers enriched with fibronectm and heparan suifate were compared with non enriched bilavered collagen barriers using the GTR technique in experimentally produced osseous defects un 12 maxillarv canines in eight doRs. Histolojjic and his- Stuart Jay Froum. DDS, 17 West S-tth .Street. New York. NY 10019. (omoiphometric examinations 10 days posLsurgery revealed a .short l.'SA.