Year : 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
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.
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Dufare DB. Biomaterials for periodontal regeneration: A brief overview.J Oral Res Rev 2021;13:76-80
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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: https://www.jorr.org/text.asp?2021/13/1/76/309436
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. 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. 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. 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. Nyman et al., 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, and multicenter human clinical trials, 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 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 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.
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,, whereas some reported healing by both long junctional epithelium and periodontal regeneration, while some studies noticed healing only by long junctional epithelium and osseous repair.
Efficacy of allograft
Two studies reported almost complete periodontal reconstitution., Some reported combination of long junctional epithelium and periodontal regeneration/connective tissue attachment. 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. 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 showed insufficient evidence to support bone graft, whereas another 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, variations in techniques for commercial preparations, and particle size. 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.
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 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. Application of EMD is a technique sensitive procedures and contamination of the material jeopardizing the regenerative potential.
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, 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 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, 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 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, 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.
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.
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