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Enhanced Osteoinductivity of Demineralized Bone Matrix with Noggin Suppression in Polymer Matrix.

ABSTRACT: Demineralized bone matrix (DBM), a potential alternative to autologous bone-graft, has been increasingly used for clinical bone repair; however, its application in larger defects isn't successful partly due to the rapid dispersion of DBM particles and relatively lower osteoinductivity. Here, a novel strategy is created to complement the osteoinductivity of DBM by incorporating DBM in biopolymer hydrogel combined with the abrogation of BMP antagonism. Combined treatment of DBM + noggin-suppression displays increased osteogenic potency of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. Injectable chitosan (MeGC)-based hydrogel with heparinization (Hep-MeGC) is further developed to localize and stabilize DBM. Noggin-suppression reveals the significant increase in osteogenesis of hBMSCs in the photopolymerizable Hep-MeGC hydrogels with the encapsulation of DBM. Moreover, the combination of DBM + noggin-suppression in the injectable Hep-MeGC hydrogel displays a robust bone healing in mouse critical-sized calvarial defects in vivo. The mechanistic analysis demonstrates that noggin-suppression increased DBM osteoinductivity by stimulating endogenous BMP/Smad signals. These results have shown promise in DBM's ability as a prominent bone grafting material while being coupled with gene editing mechanism and a localizing three-dimensional scaffold. Together, this approach poses a significant increase in the efficiency of DBM-mediated craniofacial bone repair and dental osteointegration.

SUBMITTER: Chen C

PROVIDER: S-EPMC7877805 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDemineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken bisphosphonates to prevent osteoclast-mediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors.MethodsSex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken bisphosphonates and one who had not taken bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry.ResultsNine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without bisphosphonates and 1.9 ± 0.7 for those with bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity.ConclusionsDemineralized bone matrix samples from donors treated with bisphosphonates and donors not treated with bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling.

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Enhanced Osteoinductivity of Demineralized Bone Matrix with Noggin Suppression in Polymer Matrix.

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