The native periodontium includes cementum, a functionally oriented periodontal ligament, alveolar bone and gingiva. Pathologic and/or traumatic events may lead to the loss or damage of this anatomical structure. Since the 1970s, a number of procedures have been investigated in an attempt to restore such lost tissues. Numerous clinical trials have shown positive outcomes for various reconstructive surgical protocols. Reduced probing depths, clinical attachment gain, and radiographic bone fill have been reported extensively for intrabony and furcation defects following scaling and root planing, open flap debridement, autogenous bone grafting, implantation of biomaterials including bone derivatives and bone substitutes, guided-tissue regeneration (GTR) procedures, and implantation of biologic factors, including enamel matrix proteins. Histological studies have shown that various surgical periodontal procedures can lead to different patterns of healing. Healing by formation of a long junctional epithelium (epithelial attachment) is characterized by a thin epithelium extending apically interposed between the root surface and the gingival connective tissue (4, 23). Connective tissue repair (new attachment) is represented by collagen fibers oriented parallel or perpendicular to a root surface previously exposed to periodontal disease or otherwise deprived of its periodontal attachment. In contrast, periodontal regeneration is characterized by de novo formation of cementum, a functionally oriented periodontal ligament, alveolar bone, and gingiva (restitutio ad integrum). Nevertheless, it would be naive to expect these to occur as distinctly separate biologic outcomes following reconstruction of the periodontal attachment. For example, periodontal regeneration should be expected to include elements of a new, as well as an epithelial, attachment. Predictability of outcomes following surgical procedures is of fundamental importance in medicine. As periodontal-regenerative procedures are time consuming and financially demanding, there is increasing interest by clinicians to learn of factors that may influence the clinical outcome following periodontal reconstructive surgery in order to provide the best possible service to patients. This goal can only be achieved if biological aspects of wound healing and regeneration are taken into consideration. The objectives of the present article are to provide an overview of wound healing following periodontal surgical procedures, to discuss the basic principles of periodontal regeneration, and to illustrate the factors that influence this process.

Biology and principles of periodontal wound healing/regeneration.

Background: Alveolar bone regeneration is frequently necessary prior to placement of implants. Efforts to improve wound healing have focused on factors that may enhance bone formation following guided bone regeneration (GBR) techniques alone or in combination with bone replacement graft materials. Recent reports suggest that platelet-rich plasma (PRP), presumably high in levels of peptide growth factors, may enhance the formation of new bone when used in combination with autogenous graft material. Methods: In this report, the clinical and radiographic results are presented on 15 consecutively treated patients using autologous PRP in combination with freeze-dried bone allograft (FDBA) for sinus elevation and/or ridge augmentation. FDBA and PRP (0.5 g/2cc PRP) were mixed and placed as a composite graft material. A gel formed by mixing autologous thrombin-rich plasma with PRP (1:4 ratio) was used to cover the graft material. Core biopsies of grafted areas were obtained in several patients as part of implant ...

Alveolar Ridge and Sinus Augmentation Utilizing Platelet‐Rich Plasma in Combination With Freeze‐Dried Bone Allograft: Case Series

Recombinant human bone morphogenetic protein-2 is an osteoinductive protein that plays a pivotal role in bone growth and regeneration. Several hundred studies were conducted in the past 7 years in numerous animal models to establish unequivocally the efficacy, safety, mechanism of action, pharmacokinetics, and surgical handling properties of recombinant human bone morphogenetic protein-2, building a solid foundation for clinical development programs. Pilot clinical trials have shown the feasibility and safety of recombinant human bone morphogenetic protein-2 treatment, and defined the effective dose for its use in open long bone fractures and for augmentation or preservation of the alveolar bone in the dental ridge. Prospective observational clinical studies helped define clinical efficacy end points, identify significant variables, and estimate appropriate population sample size for pivotal clinical trials. Pivotal clinical trials of recombinant human bone morphogenetic protein-2 are underway in patients with open tibial shaft fractures and in patients with a deficiency of the alveolar ridge.

Clinical evaluation of recombinant human bone morphogenetic protein-2.

Potential applications and delivery strategies for bone morphogenetic proteins.

Aim: The purpose of the present review was to determine the clinical effect of the use of bioactive agents (BAs) for the treatment of intra-osseous and furcation defects. Material and Methods: The effectiveness of the BAs was evaluated when used in addition to open flap debridement either alone or in association with grafts and/or guided tissue regeneration (GTR). Among the included agents, recombinant human platelet-derived growth factor-BB (rhPDGF-BB), platelet-rich plasma (PRP), commercially available enamel matrix derivative (cEMD) and peptide P-15 (P-15) have been clinically tested for treating periodontal defects. Results and Conclusions: The results of the present review indicate that: (1) cEMD either alone or in combination with grafts can be effectively used to treat intra-osseous defects and the clinical results appear to be stable long term; (2) the additional use of a graft seems to enhance the clinical outcome of cEMD; (3) the combined use of rhPDGF-BB and P-15 with a graft biomaterial has shown beneficial effects in intra-osseous defects; (4) contrasting results were reported for PRP and graft combinations; and (5) limited evidence supports the use of BAs either alone or in association with graft/GTR for the treatment of furcation defects.

Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration

The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) concentration on regeneration of alveolar bone and cementum, and on associated root resorption and ankylosis. Contralateral, critical size, supra-alveolar, periodontal defects were surgically produced and immediately implanted with rhBMP-2 in an absorbable collagen sponge (ACS) carrier in 8, young adult, male, beagle dogs. 6 animals received rhBMP-2/ACS (rhBMP-2 at 0.05, 0.10, or 0.20 mg/mL; total construct volume/defect approximately 4.0 mL) in contralateral defects following an incomplete block design. 2 animals received rhBMP-2/ACS (rhBMP-2 at 0 and 0.10 mg/mL) in contralateral defects (controls). The animals were euthanised at 8 weeks post-surgery and block sections of the defects were collected for histologic and histometric analysis. Supra-alveolar periodontal defects receiving rhBMP-2 at 0.05, 0.10, or 0.20 mg/ml exhibited extensive alveolar regeneration comprising 86%, 96%, and 88% of the defect height, respectively. Cementum regeneration encompassed 8%, 6%, and 8% of the defect height, respectively. Root resorption was observed for all rhBMP-2 concentrations. Ankylosis was observed in almost all teeth receiving rhBMP-2. Control defects without rhBMP-2 exhibited limited, if any, evidence of alveolar bone and cementum regeneration, root resorption, or ankylosis. Within the selected rhBMP-2 concentration and observation interval, there appear to be no meaningful differences in regeneration of alveolar bone and cementum. There also appear to be no significant differences in the incidence and extent of root resorption and ankylosis, though there may be a positive correlation with rhBMP-2 concentration.

Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment.

This report describes observations of healing following guided tissue regeneration (GTR) including surgical implantation of the prostaglandin E1 analog misoprostol with calcium-layered methacrylate particles. Critical size, supra-alveolar periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in 4 beagle dogs. Wound management included soaking with a 24 microg/ml misoprostol solution and implantation of the misoprostol/methacrylate composite. One jaw quadrant per animal was prepared for GTR using expanded polytetrafluoroethylene membranes. The gingival flaps were coronally advanced and sutured to submerge the teeth. The tissues covering the surgical sites daily received topical misoprostol in an oral adhesive over the 4-week healing interval. Upon euthanasia, tissue blocks were prepared for histometric analysis of regeneration of alveolar bone and cementum, root resorption and ankylosis. The defect area underneath the membrane and the density of methacrylate particles were recorded for the GTR defects. The methacrylate particles appeared encapsulated in a dense connective tissue without signs of an inflammatory reaction, some in contact to newly formed bone. Alveolar bone regeneration height averaged (+/-SD) 1.2+/-1.0 and 1.0+/-0.6 mm for GTR and non-GTR defects, respectively. Corresponding values for bone regeneration area were 1.3+/-1.0 and 0.7+/-0.5 mm2. Cementum regeneration was confined to the apical aspect of the defects. Small areas of root resorption and ankylosis were observed for all teeth. Bone regeneration area correlated positively to the defect area and negatively to the density of methacrylate particles in the GTR defects. The histologic observations suggest that the methacrylate composite has marginal potential to promote bone and cementum regeneration under provisions for GTR.

Periodontal repair in dogs: histologic observations of guided tissue regeneration with a prostaglandin E1 analog/methacrylate composite.

Background: Although the need for "adequate" amount of keratinized tissue (KT) for periodontal health is questionable, the mucogingival junction (MGJ) often serves as a measurement landmark in periodontal evaluations. Limited information is available on the reproducibility of KT width (KTW) assessment. The purpose of this study was to assess intra- and inter-examiner reproducibility in measuring KTW by using 3 different methods to identify MGJ location. Methods: Fifteen patients provided 17 teeth which had undergone a gingival augmentation procedure (connective tissue graft; surgery group) and an equal number of contralateral, non-treated teeth (control group). At the midbuccal aspect of each tooth, KTW was assessed by 2 independent examiners after MGJ identification by the visual (VM), functional (FM), and visual with histochemical staining (HM) method. Data analysis was based on intra-class correlation coefficients (ICC) and 3-way analysis of variance (ANOVA) for differences between replicate measuremen...

Intra- and inter-examiner reproducibility in keratinized tissue width assessment with 3 methods for mucogingival junction determination.

Background: HLA-B27 transgenic rats exhibit generalized, severe inflammatory reactions and spontaneously develop arthritis and chronic gastrointestinal inflammation, as well as inflammatory lesions in other tissues. Our hypothesis was that HLA-B27 rats would also be susceptible to inflammatory periodontal disease, and therefore alveolar bone loss. The purpose of this investigation was to compare the naturally occurring alveolar bone loss in HLA-B27 and wild type rats. Methods: Age- and sex-matched HLA-B27 transgenic (TG) and wild type Fischer 344 (WT) female retired breeders, and their age-matched male WT breeding mates, were examined for alveolar bone loss (ABL). Thirty-eight animals were used: twelve, 20, and 6 animals were 6, 8, and 12 months old, respectively. ABL was measured as the exposed root surface area (mm2) in the defleshed maxilla and mandible. Results: The coefficient of variation for replicate ABL measurements was 4.4%. For the 6- and 8-month age groups, ABL was significantly greater in TG ...

HLA-B27 Transgenic Rats Are Susceptible to Accelerated Alveolar Bone Loss

OBJECTIVE: Patients with arthritis and Crohn9s disease may be more susceptible to periodontitis associated alveolar bone loss (ABL). HLA-B27 transgenic (TG) rats spontaneously develop arthritis and colitis. Based on the hypothesis that TG rats would also be susceptible to ABL, we compared the naturally occurring ABL in TG and Fischer 344 wild-type (WT) rats. METHODS: Eighteen TG and 18 WT virgin female rats were used. Pairs (I TG, I WT) were housed in suspended wire cages. At age 2.6, 6, and 11 months, 8, 5, and 5 pairs were sacrificed, respectively. ABL was measured as exposed molar root surface area (mm2). Western blotting was used for analysis of serum reactivity against bacteria associated with arthritis, colitis, and periodontitis development. RESULTS: At 2.6 months of age, there was no difference in ABL between TG and WT rats. At 6 and 11 months ABL was significantly greater in TG animals by 28% and 53%, respectively. For TG rats, ABL was significantly different between the 3 age groups. For WT rats, ABL was not significantly different between 6 and 11 months. Western blotting revealed distinct TG serum reactivity against extracts of Bacteroides vulgatus, B. fragilis, Prevotella intermedia, and to a lesser extent against extracts of B. forsythus. CONCLUSION: The accelerated ABL in HLA-B27 TG rats is an adult onset condition, independent of husbandry conditions or parity status. HLA-B27 rats exhibit strong immunoreactivity against bacteria implicated in arthritis, colitis, and periodontitis.

https://www.jrheum.org/content/jrheum/29/6/1244.full.pdf

Paola Guglielmoni

Papers

Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment.

Periodontal repair in dogs: histologic observations of guided tissue regeneration with a prostaglandin E1 analog/methacrylate composite.

Intra- and inter-examiner reproducibility in keratinized tissue width assessment with 3 methods for mucogingival junction determination.

HLA-B27 Transgenic Rats Are Susceptible to Accelerated Alveolar Bone Loss

Accelerated alveolar bone loss in HLA-B27 transgenic rats: An adult onset condition