Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect

Abstract

Injectable chitosan microparticles were prepared using a simple coacervation method under physiologically friendly conditions by eliminating oil or toxic chemical, and employing low temperature and pressure for growth factor stability. Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the chitosan microparticles by two methods: encapsulating and coating techniques. These microparticles were tested in vivo to determine the biological response in a rat femoral bone defect at 6 and 12 weeks. Four groups (n=10) were tested which include two groups for BMP-7 incorporated microparticles (by two techniques), microparticles without BMP-7, and defect itself (negative control). Healthy bone formation was observed around the microparticles, which were only confined to the defect site and did not disperse. Histology indicated minor inflammatory response around the microparticles at 6 weeks, which reduced by 12 weeks. Micro-CT analysis of bone surface density and porosity was found to be significantly more (p<0.05) for microparticles containing groups, in comparison with controls, which suggests that the new bone formed in the presence of microparticles is more interconnected and porous. Collagen fibrils analysis conducted using multiphoton microscopy showed significant improvement in the formation of bundled collagen area (%) in microparticles containing groups in comparison with controls, indicating higher cross-linking between the fibrils. Microparticles were biocompatibe and did not degrade in the 12 week implant period.

Elastin-derived scaffolding associated or not with bone morphogenetic protein (BMP) or hydroxyapatite (HA) in the repair process of metaphyseal bone defects

“…Histologically, in the unfilled defects, CG, bone formation was initiated in the deepest region of the defect from pre-existing trabeculae and spread toward the cortical space. Cortical bone formation was slow and incomplete because it failed to regenerate the metaphyseal cortex observed in normal mature bone at 42 days after surgery [29]. Failure to regenerate these bone defects is supported by preliminary studies that claim to be critical size defects requiring reconstructive procedures [11,25,[30][31][32].…”

The interaction of chitosan and BMP‐2 tuned by deacetylation degree and pH value

“…The CS‐BMP‐2 system has attracted great interest due to its potential use in orthopedic treatment and bone tissue engineering applications, since BMP‐2 has osteoinductive effect, but has a very short half‐life in the human body, and CS is thought to be osteoconductive . Thus, CS scaffolds with growth factors (BMP‐2 or BMP‐7) are deemed to be potential substitutes . However, detailed interaction mechanisms between the CS and BMP‐2 are difficult to explore distinctly by common experimental methods.…”

“…22 Thus, CS scaffolds with growth factors (BMP-2 or BMP-7) are deemed to be potential substitutes. 23,24 However, detailed interaction mechanisms between the CS and BMP-2 are difficult to explore distinctly by common experimental methods. The traditional experimental method for investigating the interactions between CS with different DDs and pH conditions and BMP-2 needs to prepare a large number of samples.…”

Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing

“…Chitosan is a natural polymer chemically constituted by β (1–4) linked d ‐glucosamine residues with N ‐acetyl‐glucosamine side chains. Chitosan has been used for several biomedical applications, namely for bone tissue engineering studies . We have previously reported the development of an immunomodulatory strategy that results from the incorporation of RvD1, in a porous 3D chitosan (Ch) scaffold (Ch + RvD1).…”

“…Chitosan has been used for several biomedical applications, namely for bone tissue engineering studies. [16][17][18] We have previously reported the development of an immunomodulatory strategy that results from the incorporation of RvD1, in a porous 3D chitosan (Ch) scaffold (Ch 1 RvD1). Using this strategy, we were able to trigger in vivo a shift in the macrophage response toward a M2 reparative response using a rodent air-pouch model of inflammation.…”