Journal of Oral Research and Review

: 2021  |  Volume : 13  |  Issue : 1  |  Page : 76--80

Biomaterials for periodontal regeneration: A brief overview

Dhiraj B Dufare 
 Department of Periodontia, Dr. R. Ahmed Dental College and Hospital, Kolkata, West Bengal, India

Correspondence Address:
Dhiraj B Dufare
Department of Periodontia, Dr. R. Ahmed Dental College and Hospital, Kolkata, West Bengal


The aim of periodontal regenerative therapy is to restore the original architecture and function of lost periodontal tissues as a result of trauma or following destructive periodontal diseases. This review includes the biological principles, efficacy, and effectiveness of different biomaterials and their limitation in periodontal regeneration. Various human clinical trials showed a successful periodontal regeneration with different biomaterials. The regenerative potential of biomaterials was assessed truly by human histological study. However, there were a limited number of human histological evidences to demonstrate the true regenerative potential of biomaterials; further human histological studies were required to establish strong evidences for application of biomaterials in the regeneration of periodontium.

How to cite this article:
Dufare DB. Biomaterials for periodontal regeneration: A brief overview.J Oral Res Rev 2021;13:76-80

How to cite this URL:
Dufare DB. Biomaterials for periodontal regeneration: A brief overview. J Oral Res Rev [serial online] 2021 [cited 2021 Aug 4 ];13:76-80
Available from:

Full Text


Periodontal regeneration is the reconstitution of the lost periodontium as a result of trauma or diseases to restore original architecture and function of the periodontium.[1] According to a position paper from American academy of Periodontology (AAP), regenerative periodontal procedures include soft-tissue graft, guided tissue regeneration (GTR), bone replacement grafts, root bio-modification, and a combination thereof, for osseous, furcation, and recession defects.[2] The objectives of periodontal regenerative therapy were to augment the periodontal attachment and bone level of periodontally compromised tooth and decrease pocket depth along with limited/or minimal soft tissue recession. The outcomes of a regenerative periodontal treatment were evaluated clinically by means of periodontal probing, radiographs, and re-entry evaluation. However, these methods are unfortunate for signifying true attachment gain. The efficacy of a periodontal regenerative therapy was assessed only by means of histology/histological method. From a biological point of view, periodontal treatment was considered as regenerative procedures when controlled animal histological studies affirming new cementum, periodontal ligament (PDL), and alveolar bone.[3] A strong native regenerative potential of the periodontium can be influenced by local and systemic factors.

 Different Biomaterials for Periodontal Regeneration

Barrier membrane/guided tissue regeneration

Basis for the development of the GTR principle was based on the understanding that the PDL has an essential significance to the regenerative processes of the tooth-supporting structure. The GTR was the first technique to be used for periodontal regeneration that had a sound biological principle.

Biological principle for the use of guided tissue regeneration

The rationale behind the GTR concept was based on the use of a physical barrier membrane between the soft-tissue flap and the root surface that provides space by deflecting migration/proliferation of gingival epithelium and connective tissue cells from the root surface during early healing phases and allows/favors the migration/proliferation of cells from the PDL and bone cells to repopulate root surface.

Efficacy and effectiveness of guided tissue regeneration membrane

The PDL cells possibly form a new connective tissue attachment only if the epithelium and gingival connective tissue were not permitted to occupy the wound area adjacent to the root surface.[4] Nyman et al.,[5] in a landmark proof of principle study established that by using a Millipore filter, gingival epithelial and connective tissue cells were not permitted to repopulate the periodontal wound could resulting in periodontal regeneration. These treatment concepts were eventually named GTR. The barrier membranes mainly contribute to wound stability and space provision and to a lesser extent in the compartmentalization of tissue. Systematic reviews[6],[7] and multicenter human clinical trials[8],[9] support the efficacy and effectiveness of barrier membrane in reducing the pocket depth and improving clinical attachment level (CAL) and bone level gain in the intrabony defect. A systematic review[6] and AAP position paper in 2005 found that there was no statistically significant difference between nonresorable and bioabsorbable membrane.

Limitations of the barrier membrane

Delayed wound healing and poor regenerative outcomes are the consequences of membrane exposure, bacterial contamination, and infection. Bioresorable membrane lack structural rigidity, which result into the collapse of membrane onto the root surface as a result of pressure from overlying soft tissue flap leads to space loss which in turn compromised the outcomes of regenerative therapy.[ 10] Machtei[11] in his meta-analysis concluded that membrane exposure following GTR and GBR has remarkably deleterious effects on bone formation.

Bone graft/bone substitutes

Autogenous bone, allogenic bone, xenogenic bone, and alloplastic materials are collectively referred to as bone filler, all have been used with the aim of achieving periodontal regeneration.[12]

Biological principles for the use of bone graft/bone substitutes

The biological rationales behind the use of bone graft and or alloplastic materials for regenerative therapy were based on one of the following properties: (1) osteogenesis – contains bone-forming cells, (2) osteoconduction – scaffold for bone formation, and (3) osteoinduction – the matrix of the bone graft contains bone inducing substances.

Efficacy of autograft

Some of the human histological studies reported complete reconstruction of periodontal tissue, i.e., the complete resolution of the defect,[13],[14] whereas some reported healing by both long junctional epithelium and periodontal regeneration,[15] while some studies noticed healing only by long junctional epithelium and osseous repair.[16]

Efficacy of allograft

Two studies reported almost complete periodontal reconstitution.[17],[18] Some reported combination of long junctional epithelium and periodontal regeneration/connective tissue attachment.[19] No studies to date have demonstrated complete defect resolution, but equally, none has reported any significant inflammation.

Efficacy of xenograft

Partial periodontal regeneration was observed, but none of the studies reported complete regeneration and no information on the degree of inflammation was provided.

Efficacy of alloplast

Healing was predominantly characterized by a long junctional epithelium and connective tissue encapsulation of the graft particles. Periodontal or cementum regeneration was usually limited to the apical parts of the defect. Partial periodontal regeneration was observed, but none of the studies reported complete defect resolution and remarkably little inflammation was observed.

Efficacy and effectiveness of bone graft/bone substitute

Periodontal and bone regeneration supported by bone graft materials when used in combination with GTR is by space provision rather than the osteoconductive properties of the grafting material.[20] The ability of bone graft/bone substitute materials to restore lost connective tissue attachment is missing. Biomaterial particles demonstrated new bone, especially in proximity to the former alveolar bone, signifying biocompatibility rather than an osteoconductive or osteoinductive properties. The native regenerative potential of the periodontium does not seem to improve by bone graft/bone substitute materials. With regard to periodontal regeneration, which includes the formation of new connective tissue attachment to the root surface, currently available data are not promising. Histological evidence of new connective tissue attachment is limited. No large-scale multicenter human clinical trial on bone replacement grafts has ever been performed, and hence, the applicability of these results to clinical practice remains to be established. One systematic review[21] showed insufficient evidence to support bone graft, whereas another[22] showed that bone graft materials provide a significant clinical improvement in periodontal osseous defect.

Limitations of bone graft/substitute

In preparations of allograft, limiting factors were donor age,[23] variations in techniques for commercial preparations,[24] and particle size.[25] Autogenous bone usually involves a second surgical site which, in turn, increases patient morbidity and the volume of graft available is also invariable. The resorption of autogenous bone graft is unpredictable.

Enamel matrix derivative

Biological principle of enamel matrix derivative

The enamel matrix derivative (EMD) consists of a heterogeneous mixture of proteins containing amelogenins as a major component. These biologically active molecules capable of encouraging the development of an acellular cementum together with collagenous fibers that develop over newly formed bone.[26]

Efficacy and effectiveness of enamel matrix derivative

Human clinical trials, systematic reviews, and meta-analysis provide significant additional benefits of EMD in terms of pocket depth reduction, CAL gain, and radiographic bone level in intrabony defects. A large multicenter human clinical trial[27] demonstrated both efficacy and effectiveness of EMD in intrabony defects.

Limitations of enamel matrix derivative

One of the possible drawbacks associated with EMD preparation is its gel-like consistency after reconstitution. When used in intrabony defects, it may limit the space provision potential of the preparation.[28] Application of EMD is a technique sensitive procedures and contamination of the material jeopardizing the regenerative potential.

Growth/differentiation factor

Growth/differentiation factors (GDFs) represent a large family of polypeptidic molecules that modulate cell responses such as cell attachment/adhesion, cell survival, proliferation, chemotaxis, and differentiation. Bone, PDL, and cementum are highly differentiated tissues and different growth factors regulate the signaling events and their neoformation during wound healing. Different growth factors have specific functions on specific target cells in wound healing and their delicate balance is required for optimal tissue repair.

Biological principles of growth factors

Biological rationale behind the use of several growth factors was these biologically active molecules are able to regulate proliferation, accelerate activity and/or stimulate differentiation of key cells involved in the periodontal regenerative process, such as cementoblast, PDL fibroblast, and osteoblast, encouraging successful regeneration of lost tissue.

Different types of growth factors

Platelet-derived growth factor – BB

Efficacy and effectiveness of platelet-derived growth factor –BB

Two multicenter studies[29],[30] on recombinant human (rh) platelet-derived growth factor (PDGF–BB) in the treatment of intrabony defect have been conducted. Both the studies show added benefits compared with controls in terms of bone gain, whereas one study[29] did not induce a statistically significant difference in terms of CAL gain. Efficacy and effectiveness of human PDGF-BB have to be further explored before clinical application.

Fibroblast growth factor-2

Efficacy and effectiveness of fibroblast growth factor -2

Two multicenter studies[31],[32] on fibroblast growth factor (FGF-2) in the treatment of intrabony defect have been conducted. Both the studies show added benefits compared with controls in terms of bone gain, whereas no study demonstrated a statistically significant difference in terms of CAL gain. Both efficacy and effectiveness of FGF-2 have to be further explored before clinical application.

Bone morphogenic protein-2

Efficacy and effectiveness of bone morphogenic protein -2

Long-term follow-up with bone morphogenic protein (BMP)-2 in some human trials supported its use in hard tissue augmentation. No human studies were available regarding its use in true periodontal regeneration. Some reports showed that BMP-2 stimulates root resorption and ankylosis. The Food and Drug Administration approved BMP-2 for sinus augmentation and alveolar ridge augmentation associated with extraction socket defects. A randomized controlled trial[33] provides evidence that rh GDF-5/β tricalcium phosphate may substantially support periodontal wound healing/regeneration. Further studies with a larger sample size will have to be conducted to verify these findings.

Limitations of growth/differentiation factor

They lack structural integrity and rigidity to help in the provision of space and blood-clot stabilization. Probably because of proteolytic breakdown receptor-mediated endocytosis and solubility of the delivery vehicle, growth factors undergo unsteadiness and rapid dilution from the target sites,[34] so their half-lives are remarkably reduced and the period of exposure should not be enough to act on osteoblast, cementoblast, or PDL cells. Therefore, growth factor delivery by different methods needs to be considered.[35]


GTR has a sound biological principle for periodontal regeneration. However, various human clinical studies support the use of other biomaterials such as bone graft/bone substitute materials, enamel matrix derivative, and several GDFs for periodontal regeneration. The regenerative potential of biomaterials was assessed truly by human histological study. However, there were a limited number of human histological evidences to demonstrate the true regenerative potential of biomaterials; further human histological studies were required to establish strong evidences for application of biomaterials in the regeneration of periodontium.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Catón J, Bostanci N, Remboutsika E, de Bari C, Mitsiadis TA. Future dentistry: Cell therapy meets tooth and periodontal repair and regeneration. J Cell Mol Med 2011;15:1054-65.
2Greenwell H; Committee on Research, Science and Therapy American Academy of Periodontology. Position paper: Guidelines for periodontal therapy. J Periodontol 2001;72:1624-8.
3Polimeni G, Xiropaidis AV, Wikesjo UM. Biology and principles of periodontal wound healing/regeneration. Periodontology 2000 2006;41:30-47.
4Karring T, Nyman S, Gottlow J, Laurell L. Development of the biological concept of guided tissue regeneration–animal and human studies. Periodontol 2000 1993;1:26-35.
5Nyman S, Lindhe J, Karring T, Rylander H. New attachment following surgical treatment of human periodontal disease. J Clin Periodontol 1982;9:290-6.
6Murphy KG, Gunsolley JC. Guided tissue regeneration for the treatment of periodontal intrabony and furcation defects. A systematic review. Ann Periodontol 2003;8:266-302.
7Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ. Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev 2006;19:CD001724.
8Tonetti MS, Cortellini P, Suvan JE, Adriaens P, Baldi C, Dubravec D, et al. Generalizability of the added benefits of guided tissue regeneration in the treatment of deep intrabony defects. Evaluation in a multi-center randomized controlled clinical trial. J Periodontol 1998;69:1183-92.
9Cortellini P, Tonetti MS, Lang NP, Suvan JE, Zucchelli G, Vangsted T, et al. The simplified papilla preservation flap in the regenerative treatment of deep intrabony defects: Clinical outcomes and postoperative morbidity. J Periodontol 2001;72:1702-12.
10Haney JM, Nilvéus RE, McMillan PJ, Wikesjö UM. Periodontal repair in dogs: Expanded polytetrafluoroethylene barrier membranes support wound stabilization and enhance bone regeneration. J Periodontol 1993;64:883-90.
11Machtei EE. The effect of membrane exposure on the outcome of regenerative procedures in humans: A meta-analysis. J Periodontol 2001;72:512-6.
12Committee on Research, Science and Therapy of the American Academy of Periodontology. Tissue Banking of Bone Allograft used in Periodontal Regeneration. J Periodontol 2001;76:834-8.
13Dragoo MR, Sullivan HC. A clinical and histological evaluation of autogenous iliac bone grafts in humans. I. Wound healing 2 to 8 months. J Periodontol 1973;44:599-613.
14Evans RL. A clinical and histologic observation of the healing of an intrabony lesion. Int J Periodontics Restorative Dent 1981;1:20-5.
15Froum SJ, Kushner L, Stahl SS. Healing responses of human intraosseous lesions following the use of debridement, grafting and citric acid root treatment. I. Clinical and histologic observations six months postsurgery. J Periodontol 1983;54:67-76.
16Moskow BS, Karsh F, Stein SD. Histological assessment of autogenous bone graft. A case report and critical evaluation. J Periodontol 1979;50:291-300.
17Bowers G, Felton F, Middleton C, Glynn D, Sharp S, Mellonig J, et al. Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with purified bovine collagen. J Periodontol 1991;62:690-702.
18Mellonig JT. Histologic and clinical evaluation of an allogeneic bone matrix for the treatment of periodontal osseous defects. Int J Periodontics Restorative Dent 2006;26:561-9.
19Koylass JM, Valderrama P, Mellonig JT. Histologic evaluation of an allogeneic mineralized bone matrix in the treatment of periodontal osseous defects. Int J Periodontics Restorative Dent 2012;32:405-11.
20Polimeni G, Koo KT, Qahash M, Xiropaidis AV, Albandar JM, Wikesjo UM. Prognostic factors for alveolar regeneration: Effect of a space-providing biomaterial on guided tissue regeneration. J Clin Periodontol 2004;31:725-9.
21Trombelli L, Heitz-Mayfield LJ, Needleman I, Moles D, Scabbia A. A systematic review of graft materials and biological agents for periodontal intraosseous defects. J Clin Periodontol 2002;29 Suppl 3:117-35.
22Reynolds MA, Aichelmann-Reidy ME, Branch-Mays GL, Gunsolley JC. The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review. Ann Periodontol 2003;8:227-65.
23Schwartz Z, Mellonig JT, Carnes DL Jr., de la Fontaine J, Cochran DL, Dean DD, et al. Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation. J Periodontol 1996;67:918-26.
24Acarturk TO, Hollinger JO. Commercially available demineralized bone matrix compositions to regenerate calvarial critical-sized bone defects. Plast Reconstr Surg 2006;118:862-73.
25Shapoff CA, Bowers GM, Levy B, Mellonig JT, Yukna RA. The effect of particle size on the osteogenic activity of composite grafts of allogeneic freeze-dried bone and autogenous marrow. J Periodontol 1980;51:625-30.
26Hammarström L. Enamel matrix, cementum development and regeneration. J Clin Periodontol 1997;24:658-68.
27Tonetti MS, Lang NP, Cortellini P, Suvan JE, Adriaens P, Dubravec D, et al. Enamel matrix proteins in the regenerative therapy of deep intrabony defects. J Clin Periodontol 2002;29:317-25.
28Mellonig JT. Enamel matrix derivative for periodontal reconstructive surgery: Technique and clinical and histologic case report. Int J Periodontics Restorative Dent 1999;19:8-19.
29Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, et al. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: Results of a large multicenter randomized controlled trial. J Periodontol 2005;76:2205-15.
30Jayakumar A, Rajababu P, Rohini S, Butchibabu K, Naveen A, Krishnajaneya Reddy P, et al. Multi-centre, randomized clinical trial on efficacy and safety of recombinant human platelet-derived growth factor with b-tri calcium phosphate in human intra-osseous periodontal defects. J Clin Periodontol 2011;38:163-72.
31Kitamura M, Nakashima K, Kowashi Y, Fujii T, Shimauchi H, Sasano T, et al. Periodontal tissue regeneration using fibroblast growth factor-2: Randomized controlled phase II clinical trial. PLoS One 2008;3:e2611.
32Kitamura M, Akamatsu M, Machigashira M, Hara Y, Sakagami R, Hirofuji T, et al. FGF-2 stimulates periodontal regeneration: Results of a multi-center randomized clinical trial. J Dent Res 2011;90:35-40.
33Stavropoulos A, Becker J, Capsius B, Acil Y, Wagner W, Terheyden H. Histological evaluation of maxillary sinus floor augmentation with recombinant human growth and differentiation factor-5 coated beta-tri calcium phosphate (rhGDF-5/-TCP). Results of a multi center randomized clinical trial. J Clin Periodontol 2011;38:966-74.
34Anusaksathien O, Giannobile WV. Growth factor delivery to re-engineer periodontal tissues. Curr Pharm Biotechnol 2002;3:129-39.
35Anusaksathien O, Jin Q, Ma PX, Giannobile WV. Scaffolding in periodontal engineering. In: Ma PX, Eliseeff J, editors. Scaffolding in Tissue Engineering. Boca Raton, FL, USA: CRC Press; 2005. p. 427-44.