Tanta Dental Journal

: 2017  |  Volume : 14  |  Issue : 4  |  Page : 169--172

Role of combination therapy/composite graft in periodontal regeneration: A mini review

Deepa Dhruvakumar, Chandni Gupta 
 Department of Periodontology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India

Correspondence Address:
Deepa Dhruvakumar
Department of Periodontology, Subharti Dental College and Hospital, Delhi-Haridwar By-Pass Road, Meerut 250005, Uttar Pradesh


Bone grafts are necessary to provide support, fill voids, and enhance biologic repair of skeletal defects. They are desired to be bioresorbable in nature and also to present no antigen-antibody reaction. Despite of the tremendous number of bone-graft substitutes that can be used in, there is no ideal bone graft that has the function capabilities and the potentiality to reduce the need for autograft. This paper reviews the role of the combination therapy for periodontal regeneration.

How to cite this article:
Dhruvakumar D, Gupta C. Role of combination therapy/composite graft in periodontal regeneration: A mini review.Tanta Dent J 2017;14:169-172

How to cite this URL:
Dhruvakumar D, Gupta C. Role of combination therapy/composite graft in periodontal regeneration: A mini review. Tanta Dent J [serial online] 2017 [cited 2019 Jan 23 ];14:169-172
Available from: http://www.tmj.eg.net/text.asp?2017/14/4/169/221377

Full Text


Periodontitis is an inflammatory disease of the supporting tissues of the teeth caused by groups of specific microorganisms, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation, recession or both and leading to the formation of defects in the interdental and marginal bone. If left untreated, could lead to the loosening and subsequent loss of teeth [1]. Nonsurgical therapy is initiated to stop the disease activity, but if it is unsuccessful, periodontal surgery may be required to stop the progressive bone loss and regenerate the lost bone. Surgical procedures include open flap debridement, osseous surgery; it could be combined with bone grafting and/or guided tissue regeneration [2].

Regeneration is defined as a reproduction or reconstruction of a lost or injured part in such a way that the architecture and function of the lost or injured tissues are completely restored. Various materials such as autogenous grafts, allografts, xenografts, alloplasts have been aimed in the treatment of intrabony defect [2]. Assuming that their application would potentially manipulate the biological response into a regenerative rather than a predominantly reparative pattern has rendered the use of bone replacement grafts an attractive choice in certain periodontal defect configurations [3]. It had also become apparent that, if the goal of periodontal regeneration is to be realized, the problem of regeneration needs to be approached from a basic biological perspective [4]. Biologic principles supporting 'combination therapy' relate to the possibility of obtaining an additive effect from combining different regenerative principles, including osteoconductivity, and osteoinductivity, capacity for space provision and blood clot stabilization and ability to induce or accelerate the processes of matrix formation and cell differentiation that are inherent in barriers, grafts and bioactive substances. The aim of the present article is to review the role of composite graft in the future direction of regeneration.

Historical background

Among the various bone grafts used in the regeneration of intrabony defects, autogenous bone graft was most popularly used for this purpose, but the availability of the donor site and the limited quantity of the material caused limitations when the intraoral autogenous bone graft was used. To overcome the limitation of autogenous graft, allografts and xenografts were introduced in the field of periodontics. Although these materials offer a solution to some of the above problems, the question of immunogenicity and disease transfer had often been raised [5]. Therefore, considering all the above mentioned problems, alloplastic materials were introduced. These materials are synthetic, biocompatible, inorganic bone-graft substitutes which represent a possible alternative for the treatment of intrabony defects. Advantages of these materials are easier availability, eliminating the need of a donor site, and carry no risk for disease transmission [5]. Ceramics have been utilized solely as osteoconductive bone-graft matrices [6].

Evolution of composite graft concept

Composite grafts can be defined as any combination of materials that includes both an osteoconductive matrix and an osteogenic or osteoinductive material. The desire to incorporate the favourable properties of different materials into a single graft compound has led to the production of various composite grafts. Some advantageous properties of collagen over other materials include haemostatic function, allowing an early wound stabilization, chemotactic properties to attract fibroblasts and semipermeability, facilitating nutrient transfer [7]. However, its mechanical properties are relatively low (E ~ 100 MPa) in comparison to bone (E ~ 2 50GPa) and it is therefore highly cross-linked or found in composites, such as collagen–glycosaminoglycans for skin regeneration, or collagen–hydroxyapatite (HA) for bone remodelling [8],[9],[10]. Composite synthetic grafts offer an alternative that could potentially unite the three essential bone-forming properties in more controlled and effective combinations without the disadvantages found with autograft. For example, collagraft is composite of suspended fibrillar collagen and a porous calcium phosphate ceramic, in a ratio of 1: 1 and Healos includes type I collagen fibre coated with HA. In addition, HA and type I collagen composite having similar nanostructure and composition, could give promising results in periodontal regeneration [11].

The manufacture of composites is a biomimetic approach, as bone can be viewed as a composite of collagen, the principal organic component; HA, the inorganic mineral component, water and small amounts of other organic phases [12]. Not surprisingly, improvement in regeneration has been observed in composite constructs mimicking the composition and structure of bone.

Different methods for collagen–HA composite preparation include – (i) in-vitro collagen mineralization, (ii) thermally-triggered assembly of HA/collagen gels, (iii) vacuum infiltration of collagen into a ceramic matrix, (iv) enzymatic mineralization of collagen sheets, (v) water-in-oil emulsion system, (vi) freeze drying and critical point drying scaffolds and (vii) solid freeform fabrication with composite scaffolds [13].

In-vitro collagen mineralization method

Direct mineralization of a collagen substrate involves the use of calcium and phosphate solutions. Collagen can either be a fixed solid film through which calcium and phosphate ions diffuse into the fibrils [14], or as a phosphate-containing collagen solution [10], or an acidic calcium-containing collagen solution [15]. The advantage of using the first method is that the orientation of the collagen fibres can be controlled [16]. Indeed, it has been shown that the c-axis of HA crystals can be made to grow along the direction of collagen fibrils if the right conditions of mineralization are met. These conditions (pH 8–9 and T = 40°C) promote calcium ion accumulation on the carboxyl group of collagen molecules, leading to HA nucleation [10] [Table 1].{Table 1}

Benefits of composite graft

Although ceramics and collagen when used separately provide a relatively successful alternative for augmenting bone growth, the composite of the two natural materials exceed this success [13]. The ductile properties of collagen help to increase the poor fracture toughness of HA and the addition of a calcium/phosphate compound to collagen sheets provide higher stability, increases the resistance to three-dimensional swelling compared to the collagen and enhance their mechanical 'wet' properties [17]. Several other advantages including combining the osteoconductivity and bone-bonding potential of the inorganic phase with the porosity and interconnectivity of the three-dimensional construct. The most prominent natural polymer used to fabricate matrices in composite is collagen type I, probably due to its prevalence in bone's extracellular matrix and its ability to promote mineral deposition and provide binding sites for osteogenic proteins [18],[19]. Although collagen itself is an inadequate bone graft, but when combined with ceramics and growth factors, it becomes a powerful inducer of bone regeneration [20]. HA-polymer composite scaffolds can improve osteoblastic cell growth. They significantly enhance the expression of mature bone marker genes such as osteocalcin and bone sialoprotein. Finally, HA/collagen scaffolds have shown important roles in tissue engineering, with good in-vitro and in-vivo results [21],[22].


As conventional periodontal therapy has limited scope and results are not predictable, currently, bone replacements graft materials are being popularly used [23]. The interest in bone replacement grafts has emerged from the desire to fill an intrabony or furcation defect rather than radically resect surrounding intact bone tissue. The major solid components of human bone are collagen (a natural polymer, also found in skin and tendons) and a substituted HA (a natural ceramic, also found in teeth). Alloplasts (ceramics) are synthetic, inorganic, biocompatible bone substitutes that primarily function as defect fillers in the treatment of periodontal intrabony defects. They can aid in bone regeneration by a process called osteoconduction. However, ceramics (e.g. HA, tricalcium phosphate and/or coral) are brittle and does not match alone the mechanical properties of cortical bone.

On the other hand, collagen has excellent biocompatibility properties, easily degraded and resorbed by the body and allows good attachment to cells. However, its mechanical properties are relatively low in comparison to bone [8]. Although these two components when used separately provide a relatively successful alternative for augmenting bone growth, but the composite of the two natural materials exceed this success [13].

Both collagen type I and HA enhance osteoblast differentiation, but combined together, they have shown to accelerate osteogenesis. A composite matrix when embedded with human-like osteoblast cells, showed better osteoconductive properties compared to monolithic HA and produced calcification of identical bone matrix in a study conducted by Wang et al.[24]. The results of an in-vitro study conducted by Lickorish et al. [25] revealed that collagen–HA composite prepared by biomimetic process is a cytocompatible material that supports cellular attachment and proliferation. Similar, results were obtained in an in-vitro study conducted by Minabe et al. [26] where HAP-collagen complex group seemed to have positively promoted the formation of collagen fibres, based on histological examination as epithelial down growth was smaller in HAP-collagen complex group and the regenerated fibres showed an orientation perpendicular to the root surface. Sugaya et al. [27] in their histological animal study reported increased success in terms of new cementum and bone formation by using HA/collagen mix in treatment of bone defects. Currently, composite materials being tested in preclinical and clinical trials may exhibit functionality comparable to autograft and allograft. When comparing ceramic scaffolds and ceramic composite scaffolds, it was shown that collagen–HA composites performed well compared to single HA or tricalcium phosphate scaffolds in a study conducted by Wang [28]. Therefore, composite graft combines an osteoconductive matrix with bioactive agents that provide osteoinductive and osteogenic properties, potentially replicating autograft functionality. The osteoconductive matrix becomes a delivery system for bioactive agents, requiring less chemotaxis and less migration of osteoblast progenitor cells to the graft site. The direct infusion of progenitor cells could lead to more rapid and consistent bone recovery.


Composite synthetic grafts offer an alternative that could potentially unite the three essential bone-forming properties in more controlled and effective combinations without the disadvantages found with autograft. Also, the addition of collagen to a ceramic structure could provide many advantages to surgical applications: Shape control, spatial adaptation, increased particle and defect wall adhesion and the capability to favour clot formation and stabilization. The role of composite grafts as a successful graft material is still in its infancy but seems to be promising in the treatment of periodontal infrabony defects.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Newman MG, Takei HH, Klokkevold PR, Carranza FA, Novak MJ. Classification of diseases and conditions affecting the periodontium. Clinical periodontology. 10th ed.. St Louis, MO: Saunders; Elsevier India Pvt Ltd; 2006. pp. 103–104.
2Karring T, Linde J, Cortellini P. Regenerative periodontal therapy. Clinical periodontology and implant dentistry. A text book of clinical periodontology and implant dentistry. 4th ed. Oxford, UK: Blackwell Publishing Ltd; 2003. p. 650.
3Nasr HF, Aichelmann-Reidy ME, Yukna RA. Bone and bone substitutes. Periodontol 2000 1999; 19:74–86.
4Polson AM. Periodontal regeneration: current status and directions. 1st ed. Denver, CO: Quintessence Books; 1994. p. 21.
5Nery EB, Lee KK, Czajkowski S, Dooner JJ, Duggan M, Ellinger RF, et al. A veteran administration co-operative study of biphasic calcium phosphate ceramic in periodontal osseous defects. J Periodontol 1990; 61:737–744.
6Gazdag AR, Lane JM, Glaser D, Forster RA. Alternatives to autogenous bone graft: efficacy and indications. J Am Acad Orthop Surg 1995; 3:1–8.
7Yaffe A, Ehrlich J, Shoshan S. Restoration of periodontal attachment employing enriched collagen solution in the dog. J Periodontol 1984; 55:623–628.
8Clarke KI, Graves SE, Wong ATC, Triffitt JT, Francis MJO, Czernuszka JT. Investigation into the formation and mechanical-properties of a bioactive material based on collagen and calcium-phosphate. J Mater Sci Mater Med 1993; 4:107–110.
9O'Brien FJ, Harley BA, Yannas IV, Gibson L. Influence of freezing rate on pore structure in freeze-dried collagen-gag scaffolds. Biomaterials 2004; 25:1077–1086.
10Kikuchi M, Matsumoto HN, Yamada T, Koyama Y, Takakuda K, Tanaka J. Glutaraldehyde crosslinked hydroxyapatite/collagen self-organized nanocomposites. Biomaterials 2004; 25:63–69.
11Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitute: an update. Injury 2005; 36:20–27.
12Weiner S, Wagner HD. The material bone: structure mechanical function relations. Annu Rev Mater Sci 1998; 28:271–298.
13Wahl DA, Czernuszka JT. Collagen-hydroxyapatite composites for hard tissue repair. Eur Cell Mater 2006;11:43-56.
14Lawson AC, Czernuszka JT. Collagen – calcium phosphate composites. Proc Inst Mech Eng H 1998; 212:413–425.
15Bradt JH, Mertig M, Teresiak A, Pompe W. Biomimetic mineralization of collagen by combined fibril assembly and calcium phosphate formation. Chem Mat 1999; 11:2694–2701.
16Iijima M, Moriwaki Y, Kuboki Y. Oriented growth of octacalcium phosphate on and inside the collagenous matrix in vitro. Connect Tissue Res 1996; 32:519–524.
17Yamauchi K, Goda T, Takeuchi N, Einaga H, Tanabe T. Preparation of collagen/calcium phosphate multilayer sheet using enzymatic mineralization. Biomaterials 2004; 25:5481–5489.
18Sachlos E, Gotora D, Czernuszka JT. Collagen scaffolds reinforced with biomimetic composite nano-sized carbonate-substituted hydroxyapatite crystals and shaped by rapid prototyping to contain internal microchannels. Tissue Eng 2006; 12:2479–2487.
19Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci 2004; 4:743–765.
20Yunoki S, Ikoma T, Monkawa A, Marukawa E, Sotome S, Shinomiya K, et al. Three-dimensional porous hydroxyapatite/collagen composite with rubber-like elasticity. J Biomater Sci Polym Ed 2007; 18:393–409.
21Kim K, Dean D, Lu A, Mikos AG, Fisher JP. Early osteogenic signal expression of rat bone marrow stromal cells is influenced by both hydroxyapatite nanoparticle content and initial cell seeding density in biodegradable nanocomposite scaffolds. Acta Biomater 2011; 7:1249–1264.
22Zhang L, Tang P, Xu M, Zhang W, Chai W, Wang Y. Effects of crystalline phase on the biological properties of collagen-hydroxyapatite composites. Acta Biomater 2010; 6:2189–2199.
23Dumitrescu AL. Bone grafts and bone graft substitutes in periodontal therapy. Chemicals in surgical periodontal therapy. Berlin; Heidelberg: Springer-Verlag Publishing Ltd; 2011. pp. 73–144.
24Wang RZ, Cui FZ, Lu HB, Wen HB, Ma CL, Li HD. Synthesis of nanophase hydroxyapatite collagencomposite. J Mater Sci Lett 1995; 14:490–492.
25Lickorish D, Ramshaw JAM, Werkmeister JA, Glattauer V, Howlett CR. Collagen–hydroxyapatite composite prepared by biomimetic process. J Biomed Mater Res 2004; 68:19–27.
26Minabe M, Sugaya A, Satou H, Tamura T, Ogawa Y, Hori T, et al. Histological study of the hydroxyapatite-collagen complex implants in periodontai osseous defects in dogs. J Periodontol 1988; 59:671–678.
27Sugaya A, Minabe M, Tamura T, Hori T, Watanabe Y. Effects on wound healing of hydroxyapatite-collagen complex implants in periodontal osseous defects in the dog. J Periodontol Res 1989; 24:284–288.
28Wang M. Developing bioactive composite materials for tissue replacement. Biomaterials 2003; 24:2133–2151.