Histological Review of Demineralized Dentin Matrix as a Carrier of rhBMP-2

Abstract

In 2007, recombinant human bone morphogenetic protein-2 (rhBMP-2) was approved for use in humans at a concentration of 1.5 mg/mL with absorbable collagen sponges as an alternative to autogenous bone grafts for alveolar ridge augmentation, defects associated with extraction sockets, and sinus augmentation. However, the use of supraphysiological doses and the insufficient retention of rhBMP-2, when delivered through collagen sponge, result in dose-dependent side effects related to off-label use. Demineralized dentin matrix (DDM), an osteoinducing bone substrate, has been used as an rhBMP-2 carrier since 1998. In addition, DDM has both microparticle and nanoparticle structures, which do not undergo remodeling, unlike bone. In vitro, DDM is a suitable carrier for BMP-2, with the continued release over 30 days at concentrations sufficient to stimulate osteogenic differentiation. In this review, we discuss the histological outcomes of DDM loaded with rhBMP-2 to highlight the biological functions of exogenous rhBMP-2 associated with the DDM carrier in clinical applications in implant dentistry.Keywords: bone morphogenetic protein, bone substitute, demineralized dentin matrix Impact StatementDemineralized dentin matrix (DDM) has been used as an recombinant human bone morphogenetic protein (rhBMP-2) carrier and osteo-inducing bone substrate to facilitate continued release and stimulate osteogenic differentiation. In this review, we discuss the histological outcomes of DDM loaded with rhBMP-2 in order to highlight the biological functions of exogenous rhBMP-2 associated with the DDM carrier in clinical applications in implant dentistry.

Allogeneic Dentin Graft: A Review on Its Osteoinductivity and Antigenicity

“…The matrix around the eroded chambers is then re-calcified, presumably due to the diffusion of mineral ions from the new blood vessels. Osteoblasts then replace the multinucleated cells on the eroded and calcified surfaces, which start to deposit the bone matrix and cement line [ 27 , 45 ]. In extraskeletal sites, Allo-DDM showed penetration into the bone and was resorbed slower than DBM, presumably because DDM is a denser collagen matrix, and has neither vascular channels nor marrow space [ 26 ].…”

“…The minerals from the dentin matrix insulate the BMPs and interfere with the transmission of the bone morphogenetic property [ 1 , 24 , 53 ]. Demineralization of the dentin matrix not only contributes to removing allogeneic immune components including minerals and acid-soluble proteins but also to opening the dentinal tubules [ 29 , 45 ]. Additionally, after demineralization, the widened nanoporous dentinal tubules and exposed collagen fibers could help in the release of the dentin-matrix-derived growth factors, resulting in the proliferation of mesenchymal cells, activation of collagenolytic enzymes, the transformation of fibroblasts to osteoblasts, favorable cell attachment, and osteoinduction [ 1 , 5 , 6 , 24 , 53 , 54 , 55 ].…”

“…Dentinal tubules in dentin (20,000–60,000/mm 3 , approximately 3 µm diameter) are a unique spatial nanoporous structure that can be enlarged to microporous geometric structures by the demineralization process, resulting in increased porosity from 3% to 20% [ 25 , 54 , 55 , 69 ]. This modified geometry of DDM can facilitate the release of the dentin-matrix-derived growth factors, such as BMPs inside the dentin matrix, and hydroxyapatite-binding proteins, as well as the influx of proteins from host tissues [ 45 , 54 , 70 ].…”

Dentin-Derived-Barrier Membrane in Guided Bone Regeneration: A Case Report

“…The antigenicity of human dentin has been originally low because dentin is an acellular and avascular collagen matrix [ 14 ]. In addition, the demineralization process contributes to the enlargement of the dentinal tubules, which could affect the release of the dentin-matrix-derived (endogenous) growth factors, resulting in the activation of osteo-inductivity by phenotypic transformation of fibroblasts into osteoblasts [ 8 , 11 , 17 , 18 , 19 ].…”

“…In addition, a recent histological review of a demineralized dentin matrix as a carrier of rhBMP-2 implied that rhBMP-2 incorporated into DDM (rhBMP-2/DDM) might simultaneously initiate osteoclastic resorption of DDM and osteo-inductive bone healing [ 11 ]. The postulated release profile of rhBMP-2/DDM was suggested to be a sequential delivery of exogenous rhBMP-2 and the endogenous BMP in a physiological environment [ 8 ].…”