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Biomedical subjects

Samuel E Lynch

Publications and source records attributed to Samuel E Lynch.

14 recordsLinked to original sources

Effect of rhPDGF-BB delivery on mediators of periodontal wound repair.

Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of tooth-supporting structures. This investigation examined the effect of the local delivery of PDGF-BB when combined with reconstructive periodontal surgery on local wound fluid (WF) levels of PDGF-AB, vascular endothelial growth factor (VEGF), and bone collagen telopeptide (ICTP) in humans with advanced periodontitis. Sixteen patients exhibiting localized periodontal osseous defects were randomized to one of three groups (beta-TCP carrier alone, beta-TCP + 0.3 mg/mL of recombinant human PDGF-BB [rhPDGF-BB], or beta-TCP + 1.0 mg/mL of rhPDGF-BB) and monitored for 6 months. WF was harvested and analyzed for PDGF-AB, VEGF, and ICTP WF levels. Teeth contralateral to the target lesions served as controls. Increased levels of VEGF in the WF was observed for all surgical treatment groups with the 1.0 mg/mL rhPDGF-BB group showing the most pronounced difference at 3 weeks in the AUC analysis versus control (p < 0.0001). PDGF-AB WF levels were increased for the carrier alone group compared to both rhPDGFBB groups. Low-dose rhPDGF-BB application elicited increases in ICTP at days 3-5 in the wound healing process, suggesting a promotion of bone turnover at early stages of the repair process (p < 0.02). These results demonstrate contrasting inducible expression patterns of PDGF-AB, VEGF, and ICTP during periodontal wound healing in humans.

Adult↗

Effect of rhPDGF-BB on bone turnover during periodontal repair.

PURPOSE: Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of periodontia. Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a well-known biomarker of bone turnover, and as such is a potential indicator of osseous metabolic activity. The objective of this study was to evaluate the release of the ICTP into the periodontal wound fluid (WF) following periodontal reconstructive surgery using local delivery of highly purified recombinant human PDGF (rhPDGF)-BB. METHODS: Forty-seven human subjects at five treatment centres possessing chronic severe periodontal disease were monitored longitudinally for 24 weeks following PDGF regenerative surgical treatment. Severe periodontal osseous defects were divided into one of three groups and treated at the time of surgery with either: beta-tricalcium phosphate (TCP) osteoconductive scaffold alone (active control), beta-TCP+0.3 mg/ml of rhPDGF-BB, or beta-TCP+1.0 mg/ml of rhPDGF-BB. WF was harvested and analysed for local ICTP levels by radioimmunoassay. Statistical analysis was performed using analysis of variance and an area under the curve analysis (AUC). RESULTS: The 0.3 and 1.0 mg/ml PDGF-BB treatment groups demonstrated increases in the amount of ICTP released locally for up to 6 weeks. There were statistically significant differences at the week 6 time point between beta-TCP carrier alone group versus 0.3 mg/ml PDGF-BB group (p<0.05) and between beta-TCP alone versus the 1.0 mg/ml PDGF-BB-treated lesions (p<0.03). The AUC analysis revealed no statistical differences amongst groups. CONCLUSION: This study corroborates the release of ICTP as a measure of active bone turnover following local delivery of PDGF-BB to periodontal osseous defects. The amount of ICTP released from the WF revealed an early increase for all treatment groups. Data from this study suggests that when PDGF-BB is delivered to promote periodontal tissue engineering of tooth-supporting osseous defects, there is a direct effect on ICTP released from the wound.

Adult↗

New composite endpoints to assess efficacy in periodontal therapy clinical trials.

BACKGROUND: Clinical attachment level (CAL) and bone height (radiographic or clinical) are two well-accepted endpoint measures for periodontal clinical trials; however, neither one has been shown to be more predictive of long-term success than the other. We propose using a composite endpoint analysis combining clinical and radiological parameters to assess the beneficial effects on both hard and soft tissues following periodontal therapy using a single statistical test. To address this need, two composite endpoint alternatives are offered as a yardstick for clinical success; each includes the improvement in CAL and either improvement in linear bone growth or percent bone fill. METHODS: The data for composite endpoint analyses were derived from a clinical trial evaluating two concentrations of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with beta-tricalcium phosphate (beta-TCP) compared to beta-TCP plus buffer as follows: group I, beta-TCP + 0.3 mg/ml rhPDGF-BB; group II, beta-TCP + 1.0 mg/ml rhPDGF-BB; and group III, beta-TCP + buffer. The construction of composite endpoints was based on the greatest values for change, accepted by the U.S. Food and Drug Administration (FDA), for clinical attachment level (DeltaCAL), mean change in radiographic linear bone gain (LBG), and mean radiographic percent bone fill (%BF), with the following dual standards defining a successful clinical result: CAL gain > or =2.67 mm and radiographic LBG > or =1.1 mm at 6 months and CAL gain > or =2.67 mm and radiographic %BF > or =14.1% at 6 months. RESULTS: Group I (beta-TCP + 0.3 mg/ml rhPDGF-BB) demonstrated statistically significant differences from group III (active control) for both composite endpoints. For the CAL/LBG composite endpoint, 61.7% of sites in group I versus 30.4% of sites in group III met the composite endpoint benchmarks (P <0.001). For the CAL/%BF composite endpoint, 70% of sites in group I versus 44.6% of sites in group III met the composite endpoint benchmarks (P = 0.003). A non-significant trend was observed for group II versus group III with 37.9% (P = 0.20) and 55.2% (P = 0.13) of sites meeting the CAL/LBG and CAL/%BF composite endpoints, respectively. These results are further emphasized by findings demonstrating a low correlation between the individual efficacy endpoints (DeltaCAL and %BF; DeltaCAL and LBG) for each of the three treatment groups. CONCLUSIONS: Composite endpoints are advantageous in periodontal clinical trials where no single efficacy endpoint has been established as the most important. A composite endpoint, combining outcome measures of both hard and soft tissue components of the periodontium, may be preferable for assessing efficacy of periodontal regenerative therapies. Two composite endpoints are offered to meet this need.

Alveolar Bone Loss↗

rhPDGF-BB promotes healing of periodontal defects: 24-month clinical and radiographic observations.

A new therapeutic system using purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in combination with a biocompatible, osteoconductive, synthetic scaffold beta-tricalcium phosphate (beta-TCP) has recently been shown in a large-scale, prospective, blinded, randomized clinical trial to safely and effectively treat advanced periodontal osseous defects. A significant gain in clinical attachment level was observed 3 months postsurgery for sites treated with 0.3 mg/mL rhPDGF-BB + beta-TCP versus beta-TCP + buffer (active control), with this trend continuing at 6 months postsurgery. Additionally, sites treated with 0.3 mg/mL rhPDGF-BB + beta-TCP also had significantly greater radiographic linear bone gain and percent defect fill at 6 months postsurgery than sites that received bone substitute with buffer. Representative cases from the clinical trial were followed to assess their ability to maintain the initial effect of treatment observed at 6 months. At 18 or 24 months postsurgery, with the same clinical and radiographic measurement techniques used as were performed at the 6-month time point for the clinical trial, these cases demonstrated maintenance of the clinical attachment level for all but one case, with all cases demonstrating substantial increases in linear bone gain and percent bone fill versus measurements obtained at 6 months postsurgery. Substantial radiographic changes in the appearance of the defect fill were observed for both rhPDGF-BB treatment groups, consisting of increased radiopacity and bone trabeculation, indicative of increased mineralization and maturation of the bone observed 6 months postsurgery.

Adult↗

A new era in periodontal and periimplant regeneration: use of growth-factor enhanced matrices incorporating rhPDGF.

A new, powerful off-the-shelf wound healing and bone regeneration technology termed growth-factor enhanced matrix (GEM) has recently become available for clinical use. This graft material consists of a concentrated solution of pure recombinant human platelet-derived growth factor (rhPDGF-BB), the synthetic form of the body's key natural wound healing stimulator PDGF-BB, and an osteoconductive (bone scaffold) matrix. This is the first available purified, recombinant (synthetic) growth factor product and is the result of over a decade of extensive research. Clinical and animal study results with this graft material demonstrate that it is capable of simultaneously promoting wound healing, regeneration of bone, and acceleration of gingival attach-plent gain in challenging periodontal and periimplant defects.

Alveolar Bone Loss↗

Methyl cellulose gel obstructed bone formation by GBR: an experimental study in rats.

AIM: To evaluate whether bone formation under Teflon capsules may be enhanced by concomitant implantation of recombinant human platelet-derived growth factor-BB/insulin-like growth factor-I (rhPDGF-BB/IGF-I) incorporated into a methyl cellulose gel. MATERIALS AND METHODS: Fifty-five male 6-month-old albino rats of the Wistar strain were used in the study. The lateral aspect of the mandibular ramus was exposed on both sides of the jaw. In 70 sites, the periosteum was removed from the ramus, leaving the bone denuded, while in 35 sites, it was preserved. On 10 non-periosteal (P-) sites and five periosteal (P+) sites, an empty rigid teflon capsule (d=7 mm), serving as control, was placed on the ramus. In the 40 test animals, the capsule placed on the one side of the jaw was filled at random with one of three different concentrations (1,200, 600, 150 microg/ml) of rhPDGF-BB/IGF-I gel. The capsules placed on the contralateral side of the jaw contained a placebo methyl cellulose gel. Each growth factor group, defined according to the gel concentration, and the placebo group contained 10 capsules placed on the P- side and five capsules placed on the P+ side. Two months after surgery, all animals were sacrificed. RESULTS: Histologic analysis revealed that in the non-filled control capsules, the amount of new bone including the bone marrow was 29.9% and 39.7% of the capsule area on the P- and P+ sides, respectively. In the test capsules with the growth factor gel and placed on the P-sides, the amounts of new bone ranged from 5.6% to 6.3%, which were similar (p>0.05) to that formed in the capsules filled with the methyl cellulose gel (5.5%). New bone formation was larger in the capsules on the P+ sides than in those on the P- sides but was similar in the capsules with different growth factor concentrations (range 17.9-19.6%) and in those with placebo gel (21.0%). In all groups, the carrier gel was poorly absorbed and occupied most of the capsules. CONCLUSION: Local application of a methyl cellulose gel obstructed bone formation under Teflon capsules placed adjacent to uninjured cortical bone in the mandibular ramus of rats. These data suggest that another material should be utilized to deliver growth factors under Teflon membranes for guided bone regeneration.

Animals↗

Effect of Bio-Oss with or without platelet-derived growth factor on bone formation by "guided tissue regeneration": a pilot study in rats.

AIM: To investigate the effect of Bio-Oss with and without the local application of recombinant human platelet-derived growth factor (rhPDGF-BB) on bone formation under Teflon capsules. MATERIALS AND METHODS: Eight male, 6-month-old, Wistar strain rats were used in the study. In each animal, the lateral aspect of the mandibular ramus was exposed and small perforations were produced in the bone. A rigid, non-porous hemispherical teflon capsule (diameter 7 mm) was placed on the ramus in both sides of the animals. The capsule placed on the one side of the jaw was filled with Bio-Oss granules soaked in a solution of PDGF-BB (20 microg/capsule) and autogenous blood prior to placement. The capsules placed on the other side of the jaw were filled with Bio-Oss granules soaked in autogenous blood only (controls). Four rats were sacrificed after 3 months and the remaining four after 5 months. Undecalcified sections containing the capsule and surrounding tissues were prepared and analysed in the microscope. RESULTS: Histologic analysis revealed limited amounts of bone formation. Most of the space underneath the capsules was occupied by Bio-Oss particles surrounded by fibrovascular connective tissue. Given the small sample size statistical analysis was not possible, however, the mean amount of mineralized new bone in the control group (20.8%) appeared to be larger than that in the test group (6.7%). After 5 months the amount of newly formed bone appeared similar in the two groups (23.0% test, 26.0% controls). The Bio-Oss particles occupied between 31.4% and 41.1% of the capsule area at 3 months and between 34.0% and 34.7% at 5 months. Only particles adjacent to the mandibular ramus were incorporated in newly formed bone. CONCLUSION: Limited bone formation was present in the capsules grafted with Bio-Oss with or without the growth factor.

Animals↗

Platelet-derived growth factor enhancement of two alloplastic bone matrices.

BACKGROUND: The use of alloplastic matrices that mimic the mineral phase of bone has become a viable alternative to current mainstream therapies in dentistry such as allografts and autogenous grafts. Because alloplastic bone substitutes generally have relatively poor osteogenic properties, analyzing their potential as vehicles to deliver growth factors is an important step in assessing methods to enhance their clinical efficacy. The aim of these studies was to treat beta-tricalcium phosphate (beta-TCP) and calcium sulfate (CaSO(4)) with platelet-derived growth factor (PDGF)-BB to enhance the osteogenic capabilities of these materials. METHODS: In the beta-TCP studies, PDGF-BB adsorption and release were accomplished using (125)I radiolabeled growth factor and non-radioactive human recombinant PDGF at a ratio of 1:300 M. For the adsorption studies, the radiolabeled PDGF-BB/ non-radioactive PDGF solutions with resultant PDGF concentrations of 10(7) and 10(8) M were incubated with beta-TCP from 1 to 120 minutes, and the amount of adsorbed (125)I-PDGF-BB was measured using a gamma counter. Similar adsorption studies were conducted with a 30-minute incubation of beta-TCP with various PDGF concentrations. In vitro release studies were conducted with beta-TCP to which radiolabeled PDGF had been adsorbed as above. Release studies were also conducted with CaSO(4) that was hydrated with the radioactive PDGF solution described above for the TCP studies. In vivo PDGF-BB release from beta-TCP and CaSO(4) was evaluated in a mouse model, where the radioactive PDGF/non-radioactive PDGF-BB treated beta-TCP or CaSO(4) sample was inserted subcutaneously and later removed for radioactive measurement. Proliferation of human osteoblastic cells in the presence of PDGF- treated beta-TCP or CaSO(4) was assessed by (3)H thymidine incorporation. RESULTS: The absorption studies revealed that PDGF-BB was absorbed in a concentration and time-dependent manner to beta-TCP. In the in vitro release studies, approximately 45% of the adsorbed PDGF-BB was released after 10 days. In vivo release from both materials occurred faster than in vitro release. Osteoblastic cells incubated with PDGF-BB-treated matrices showed significantly (P <0.05, ANOVA) greater proliferation than with control matrices alone. CONCLUSION: These experiments demonstrate the feasibility of using PDGF-BB in combination with alloplastic materials such as beta-TCP or CaSO(4) to serve as more effective bone graft materials with enhanced osteogenic properties.

Adolescent↗

Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial.

BACKGROUND: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing. METHODS: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups. RESULTS: CAL gain was significantly greater at 3 months for group 1 (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP + buffer) (3.8 versus 3.3 mm; P = 0.032), although by 6 months, this finding was not statistically significant (P = 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P = 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linear bone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57% versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group 1 compared to group 3 (P = 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting in comparable GR. There were no serious adverse events attributable to any of the treatments. CONCLUSIONS: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.

Adult↗

Three-dimensional micro-computed tomographic evaluation of periodontal regeneration: a human report of intrabony defects treated with Bio-Oss collagen.

This study utilized three-dimensional micro-computed tomography (micro-CT) to evaluate the regenerative response to Bio-Oss Collagen when used alone or in combination with a Bio-Gide bilayer collagen membrane for the treatment of four intrabony defects (5 to 7 mm) around single-rooted teeth. The micro-CT observations are compared to the clinical, radiographic, and histologic results, which have been previously reported. After reflecting a full-thickness flap, thorough degranulation and root planing were accomplished. Bio-Oss Collagen was then used to fill the defects, and in two cases a Bio-Gide membrane was placed over the filled defect. Radiographs, clinical probing depths, and attachment levels were obtained before treatment and immediately preceding en bloc resection of teeth and surrounding tissues 9 months later. A mean pocket depth reduction of 5.75 mm and mean clinical attachment level gain of 5.25 mm were recorded. The histologic evaluation demonstrated the formation of a complete new attachment apparatus with new cementum, periodontal ligament, and alveolar bone at the level of and coronal to the calculus reference notch. Micro-CT evaluation confirmed the histologic results and demonstrated the absence of ankylosis or root resorption for all specimens. This human histologic study demonstrated that Bio-Oss Collagen has the capacity to facilitate regeneration of the periodontal attachment apparatus when placed in intrabony defects. Micro-CT observations confirmed the histologic results and enhanced the three-dimensional understanding of periodontal wound healing. The results indicate that micro-CT may be useful for three-dimensional evaluation of periodontal regenerative procedures.

Animals↗

Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone.

BACKGROUND: Purified recombinant human platelet-derived growth factor BB (rhPDGF-BB) is a potent wound healing growth factor and stimulator of the proliferation and recruitment of both periodontal ligament (PDL) and bone cells. The hypothesis tested in this study was that application of rhPDGF-BB incorporated in bone allograft would induce regeneration of a complete new attachment apparatus, including bone, periodontal ligament, and cementum in human interproximal intrabony defects and molar Class II furcation lesions. METHODS: Nine adult patients (15 sites) with advanced periodontitis exhibiting at least one tooth requiring extraction due to an extensive interproximal intrabony and/or molar Class II furcation defect were entered into the study. Eleven defects were randomly selected to receive rhPDGF-BB. Following full-thickness flap reflection and initial debridement, the tooth roots were notched at the apical extent of the calculus, the osseous defects were thoroughly debrided, and the tooth root(s) were planed/prepared. The osseous defects were then filled with demineralized freeze-dried bone allograft (DFDBA) saturated with one of three concentrations of rhPDGF-BB (0.5 mg/ml, 1.0 mg/ml, or 5.0 mg/ml). Concurrently, four interproximal defects were treated with a well accepted commercially available graft (anorganic bovine bone in collagen, ABB-C) and a bilayer collagen membrane. Radiographs, clinical probing depths, and attachment levels were obtained preoperatively (at baseline) and 9 months later. At 9 months postoperatively, the study tooth and surrounding tissues were removed en bloc. Clinical and radiographic data were analyzed for change from baseline by defect type and PDGF concentration. The histologic specimens were analyzed for the presence of regeneration of a complete new attachment apparatus coronal to the reference notch. RESULTS: The post-surgical wound rapidly healed and was characterized by firm, pink gingivae within 7 to 10 days of surgery. There were no unfavorable tissue reactions or other safety concerns associated with the treatments throughout the course of the study. In rhPDGF/allograft sites, the vertical probing depth (vPD) reduction for interproximal defects was 6.42 +/- 1.69 mm (mean +/- SD) and clinical attachment level (CAL) gain was 6.17 +/- 1.94 mm (both P < 0.01). Radiographic fill was 2.14 +/- 0.85 mm. Sites filled with ABB-C had a PD reduction and CAL gain of 5.75 +/- 0.5 and 5.25 +/- 1.71, respectively. Furcation defects treated with rhPDGF/allograft exhibited a mean horizontal and vertical PD reduction of 3.40 +/- 0.55 mm (P < 0.001) and 4.00 +/- 1.58 mm (P < 0.005), respectively. The CAL gain for furcation defects was 3.2 +/- 2.17 mm (P < 0.030). Histologic evaluation revealed regeneration of a complete periodontal attachment apparatus, including new cementum, PDL, and bone coronal to the root notch in four of the six interproximal defects and all evaluable (four of four) furcation defects treated with PDGF. Two of the four interproximal intrabony defects treated with ABB-C and membrane exhibited regeneration. CONCLUSIONS: Use of purified rhPDGF-BB mixed with bone allograft results in robust periodontal regeneration in both Class II furcations and interproximal intrabony defects. This is the first report of periodontal regeneration demonstrated histologically in human Class II furcation defects.

Adult↗

Evaluation of periodontal regeneration following grafting intrabony defects with bio-oss collagen: a human histologic report.

This study evaluated the clinical, radiographic, and histologic response to Bio-Oss Collagen when used alone or in combination with Bio-Gide bilayer collagen membrane for the treatment of four intrabony defects (5 to 7 mm) around single-rooted teeth. After reflecting a full-thickness flap, thorough degranulation and root planing were accomplished. In all cases, Bio-Oss Collagen was then used to fill the defects, and in two cases, a Bio-Gide membrane was placed over the filled defect. Radiographs, clinical probing depths, and attachment levels were obtained before treatment and immediately preceding en bloc resection of teeth and surrounding tissues 9 months later. Reduction in pocket depth and gain in clinical attachment level were observed for both treatment protocols. The histologic evaluation demonstrated the formation of a complete new attachment apparatus, evidencing periodontal regeneration that varied with defect morphology. This human histologic study demonstrated that Bio-Oss Collagen has the capacity to induce regeneration of the periodontal attachment apparatus when placed in intrabony defects.

Alveolar Bone Loss↗

Periodontal regeneration in human Class II furcations using purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with bone allograft.

This human clinical trial evaluated the clinical and histologic response to recombinant human platelet-derived growth factor-BB (rhPDGF-BB) delivered in bone allograft for the treatment of advanced Class II furcation defects. Three mandibular and one maxillary molar furcation defects were treated: Two received 0.5 mg/mL and two received 1.0 mg/mL rhPDGF-BB, in all cases mixed with DFDBA. Clinical probing depths and attachment levels were obtained presurgically and 9 months postsurgical, after which the teeth and surrounding tissues were removed en bloc. Both concentrations of rhPDGF-BB resulted in substantially improved horizontal (mean 3.5 mm) and vertical (mean 4.25 mm) probing depths and attachment levels (mean 3.75 mm). Histologic evaluation revealed periodontal regeneration, including new bone, cementum, and periodontal ligament coronal to the reference notch. Regeneration was also present coronal to the original osseous crest In one case where an enamel projection extended into the fornix of the furcation, new calcified tissue with new inserting connective tissue fibers was observed over the enamel. This study documented the favorable tissue response to rhPDGF-BB treatment at both the clinical and microscopic levels, provided the first human histologic evidence that new calcified tissue with inserting collagen fibers can occur over enamel projections within furcations, and demonstrated for the first time that complete periodontal regeneration can be achieved in advanced Class II furcation defects using a combination of purified recombinant growth factor and bone allograft.

Adult↗