Healing of autogenous intramembranous bone in the presence and absence of homologous demineralized intramembranous bone

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

“…Inspiration for in vivo developmental designs already exists with native ECM biomaterials, specifically acellular DBM grafts, which have already been shown to elicit some EC ossification in addition to the IM pathway. [26][27][28][29][30][31][32] However, as previously mentioned, DBM composition reflects the physicochemical properties of the late bone reparative stage ECM (Fig. 1) 6,9,33,34 and suggests that designs aimed at mimicking the composition of bone ECM may insufficiently elicit an EC ossification response inside healing fractures.…”

“…Inspiration for in vivo developmental designs already exists in the form of native ECM biomaterials. There is significant evidence that EC ossification occurs in acellular DBM grafts, [26][27][28][29] which inherently resemble the composition of late reparative stage bone-healing ECM. [1][2][3][4][5][6][7][8]15 In a critical-sized rat femoral defect model, Oakes et al 26 observed histological evidence of increased EC ossification foci in human DBM implants suspended in a hyaluronic acid carrier fluid compared with similar DBM implants suspended in a glycerol solution.…”

“…There exist compositional differences in bone ECM originating from IM sources during fetal development (e.g., cranium) and EC sources (e.g., femur). 44 Furthermore, DBM originating from IM and EC bone have been shown in a series of studies by Rabie et al 28,[30][31][32] to elicit different healing pathways during regeneration of parietal bone defects in New Zealand White Rabbits. The parietal bone is formed by IM ossification during fetal development, 44 Implanted subcutaneously in nude mice.…”

“…suggesting that only implants directed toward IM ossification will possess regenerative potential. However, evidence from Rabie et al 28,30,31 showed that IM and EC ossification pathways can be utilized, exclusively or in combination, to regenerate parietal defects based entirely on the source of DBM. In addition, the amount of bone regeneration was shown to be source dependent, where grafts favoring IM ossification displayed a significantly higher degree of newly formed bone observed by serial histological sectioning.…”

“…28,[30][31][32] Inductive factors such as bone morphogenic proteins (BMPs) have been implicated in bone morphogenesis dating back to their initial isolation from DBM, reviewed in chronological detail by Gruskin et al 15 Consequently, BMP-2 content, release, and bioactivity has become an important guideline in determining efficacy and quality control of commercially available DBM products. 15 BMPs, however, represent only a fraction of the growth factors in the spatiotemporal cascade of inductive molecules involved during bone healing, extensively reviewed by Mehta et al 9 Inductive signaling alone could have been responsible for the regenerative effect seen in DBM as well as account for differences seen between DBM from IM and EC sources.…”