Regeneration enhanced in critical‐sized bone defects using bone‐specific extracellular matrix protein

Abstract

Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue‐specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM‐MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence‐activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM‐MSC response to bone marrow specific ECM (BM‐ECM). BM‐ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM‐ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical‐sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM‐ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM‐ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM‐ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm4 with BM‐ECM supplementation compared to 48 ± 0.2 mm4 in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM‐ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.

Osteogenic Potential of a Biomaterial Enriched with Osteostatin and Mesenchymal Stem Cells in Osteoporotic Rabbits

“…Using biological signals such as MSC, BMP-2, OST, or zinc inside the implant to stimulate bone regeneration could be indispensable in certain situations when natural bone regeneration is not sufficient, as in the case of critical bone defects [33][34][35][36]. Several studies state that MSCs derived from adipose tissue differentiated towards the osteogenic lineage have a positive effect on osteogenesis [37,38].…”

The role of EMILIN-1 in the osteo/odontogenic differentiation of dental pulp stem cells

“…The dentin matrix and the bone matrix contain a variety of proteins and other molecules known as their extracellular matrix (ECM) components. Studies have shown that MSCs-mediated regeneration of teeth and bone tissue is regulated by ECM proteins in the microenvironment in which the cells survive [ 3 , 4 ].…”