Growth Factors For Periodontal Regeneration Research Articles

A Tribute to Gerald M. Bowers and Robert G. Schallhorn

I am privileged to be the guest editor of this issue of Clinical Advances in Periodontics, one that honors two of the greatest clinicians, educators, and scholars in the field of periodontology. It is especially appropriate that we honor Jerry Bowers and Bob Schallhorn together not only because they have collaborated on numerous articles and courses on periodontal regeneration but they also happen to be the best of friends. What I find most remarkable about Jerry and Bob is their impact on our specialty, an impact that transcends time. The articles contained in this issue of Clinical Advances in Periodontics demonstrate firsthand how Jerry and Bob’s research on regeneration continues to influence the way members of our profession practice today and will do so well into the future. Regeneration is, after all, one area of dentistry that we as periodontists can say we “own.”Their contributions to the field of regeneration also apply to dental implants diagnosed with peri-implantitis, a growing area of concern and one in which periodontists should remain in the forefront. Jerry and Bob have left an indelible mark on our profession, and future periodontists will continue to benefit from their work. Remember that Jerry was the first periodontist to look at growth factors for periodontal regeneration. He did this in 19911 when he combined osteogenin with demineralized freeze-dried bone allograft. Furthermore, his histologic evaluation of new attachment studies2,3 proved definitively that regeneration was possible. Almost all of us use combination therapies for guided tissue and/or bone regeneration. Bob Schallhorn and Pam McClain’s landmark article from 19884 continues to influence us when we use techniques to restore lost periodontium or alveolar bone. Most importantly, Bob and Jerry’s work serves as a constant reminder that: 1) the basis for our clinical decisions should be grounded in evidence; 2) adherence to surgical techniques that capitalize on the fundamentals of wound healing is essential to achieve success; and 3) the patient relies on our clinical judgment and compassion. I encourage all of you to meet these two greats at the 99th Annual Meeting of the American Academy of Periodontology in Philadelphia in September. It will be an experience you will not forget. Their enthusiasm for the field of periodontology is infectious. Their service to our chosen profession is something to be emulated. Their contributions to the boarding process and clinical studies, their leadership in the American Academy of Periodontology, and their grooming of the educators who continue to mold our future clinicians and leaders are things for which we owe them a big debt of gratitude. I have been blessed to be mentored by Bob and Jerry, who have shown me how a professional should act. Above all, they are cherished friends. Jerry and Bob, this issue is but a small token of our appreciation. Your students, your colleagues, and your friends will always admire you, and those in your profession will always be indebted to you. I thank all of you who have contributed to this special issue of Clinical Advances in Periodontics. I know that I speak for all of us when I say thank you, Jerry and Bob, from the bottom of our hearts. n

A Systematic Review of the Use of Growth Factors in Human Periodontal Regeneration

There is a large body of evidence using cells and animal models demonstrating the effectiveness of growth factors in periodontal regeneration. However, there appears to be minimal literature comparing the efficacy of growth factors in human periodontal regeneration compared to other techniques and procedures. Therefore, the aim of this study is to perform a systematic review of human studies using growth factors for periodontal regeneration and to compare the efficacy of these growth factors to other accepted techniques for periodontal regeneration. An electronic and manual search based on agreed search phrases between the primary investigator and a secondary investigator was performed to identify the use of growth factors in periodontics for the literature review. The articles that were identified by this systematic review were analyzed in detail, which included the study of their inclusion and exclusion criteria, outcome measures determination and analysis, risk of bias, adverse events, and conclusions or inference of the efficacy of growth factors to the general population. Five papers fulfilled the inclusion criteria. Two papers were identified that had sufficiently similar study design that a meta-analysis of their outcomes was possible. Most of the reported outcomes from the selected papers were descriptive. The articles demonstrated periodontal regeneration at least comparable to their respective positive controls, with only a couple of articles demonstrating significantly greater outcomes compared to their respective positive controls. Histologic evidence demonstrated greater periodontal regeneration when using growth factors compared to other regenerative techniques and an increased healing and bone maturation rate compared to other regenerative and bone augmentation techniques in these human studies. Within the limits of this systematic review, the use of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) led to greater clinical attachment level gain of ≈1 mm compared to an osteoconductive control, β-tricalcium phosphate (β-TCP). The use of rhPDGF-BB led to greater percentage bone fill of ≈40% compared to the osseoconductive control, β-TCP. Last, the use of rhPDGF-BB led to an increased rate of bone growth of ≈2 mm compared to the osseoconductive control, β-TCP.

Systematic review of the use of growth factors in periodontal regeneration

Systematic review of the use of growth factors in periodontal regeneration

Growth factors for periodontal regeneration

Periodontal tissue repair and regeneration are regulated by the local production of growth factors. However, naturally produced growth factors may not be sufficient to optimally stimulate periodontal regeneration. Exogenous growth factors can be used to supplement natural growth factors in wound healing. The authors focus on describing the mechanisms of five growth factors in periodontal regeneration: platelet-derived growth factor; fibroblast growth factor; transforming growth factor-beta; insulinlike growth factor; and bone morphogenetic protein. The objective is to encourage strategies to exploit growth factors in the stimulation of cells in periodontal regeneration, which should result from continued in vivo animal studies.

Effects of TGF-β1, PDGF-BB, and IGF-1 on the Rate of Proliferation and Adhesion of a Periodontal Ligament Cell Lineage In Vitro.

Considering the role of growth factors in periodontal regeneration, the aim of this study was to evaluate the influence of platelet-derived growth factor (PDGF)-BB, insulin-like growth factor (IGF)-1, and transforming growth factor-beta 1(TGF-β1), alone or in combination, on the rate of proliferation and adhesion of periodontal ligament (PDL) cells in vitro. After establishment and characterization of a primary culture of PDL cells, 72 culture dishes were plated with 103 cells distributed among four test groups and a control group. Test groups had PDGF-BB, TGF-β1, IGF-1, or a combination of all three added to the culture medium, whereas the control group received no growth factor. The samples were counted in triplicate 1, 3, 5, and 7 days after seeding. For the adhesion assay, 14 patients provided 30 root fragments distributed among 10 groups: scaling and root planing (SRP), SRP + growth factors, SRP + citric acid plus tetracycline (CA+T), and SRP + (CA+T) + growth factors. The data were evaluated statistically by analysis of variance complemented by Tukey, Dunnett, and Student-Newman-Keuels methods. Maximum rates of proliferation were observed at day 3 for all groups. TGF-β1 induced a 344.17% ± 58.80% increased proliferation rate over control (P <0.05), followed by the combination (277.5% ± 29.38%), PDGF-BB (238.79% ± 5.79%), and IGF-1 (233.16% ± 19.19%). Groups treated by (CA+T) showed increased numbers of cells attached to root fragments, especially SRP + (CA+T) + combination (13.25 ± 1.79), with significant differences (P <0.05) from groups treated only by SRP. This combination of growth factors stimulated a mitogenic response and favored the adhesion of PDL cells in vitro, suggesting its possible role in periodontal regeneration.

Gene-enhanced tissue engineering for dental hard tissue regeneration: (2) dentin-pulp and periodontal regeneration.

Potential applications for gene-based tissue engineering therapies in the oral and maxillofacial complex include the delivery of growth factors for periodontal regeneration, pulp capping/dentin regeneration, and bone grafting of large osseous defects in dental and craniofacial reconstruction.Part 1 reviewed the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. This manuscript will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration.

In Vitro Evaluation of the Mitogenic Effect of Platelet‐Derived Growth Factor‐BB on Human Periodontal Ligament Cells Cultured with Various Bone Allografts

Several studies have documented the role of growth factors in periodontal regeneration. It has been shown that platelet-derived growth factor (PDGF) is a potent stimulator of human periodontal ligament (PDL) cells. A variety of bone graft materials are used to treat osseous defects caused by periodontal disease. We evaluated the mitogenic effect of PDGF on human PDL cells cultured with different allografts to determine which of the allografts with or without PDGF promoted periodontal regeneration. Two human demineralized freeze-dried allografts of cortical (DFDBA) and cancellous (DFBA) bone and a non-demineralized freeze-dried allograft (FBA) from cancellous bone were used alone or supplemented with PDGF-BB. Human PDL cultures were derived from the mid-root of 2 maxillary premolars extracted for orthodontic reasons. Cells were grown separately in 24-well dishes with or without 20 mg of each bone allograft. On day 2 of quiescence, new medium was added with 10 ng/ml of PDGF-BB. DNA synthesis was estimated by measuring [3H] thymidine incorporation to determine the effects of the test agents on cell proliferation. Cells were processed and subjected to scintillation counting after 48 hours of incubation. Counts per minute (cpm/well) were determined for each sample. There was no statistically significant difference (P<0.05) on PDL cell proliferation when the allografts were used alone. PDL cells exhibited significantly greater proliferative responses to the 2 demineralized bone allografts, DFDBA and DFBA, when combined with PDGF-BB. A statistically significant difference on DNA synthesis was noticed when PDGF-BB was added to PDL cells cultured with FBA. PDL cells displayed no significant increase in mitogenic activity when cultured with PDGF-BB alone. The findings of this study demonstrate the beneficial role of DFDBA, DFBA, and FBA as synergic agents with PDGF-BB to periodontal regeneration. The significant ability of the 2 decalcified bone allografts, DFDBA and DFBA, combined with PDGF to stimulate PDL cell proliferation might be a useful adjunct in the treatment of periodontal defects.