Osteoporotic bone recovery by a bamboo-structured bioceramic with controlled release of hydroxyapatite nanoparticles.

While most bone defects can be repaired spontaneously, the healing process can be complicated due to insufficient bone regeneration when osteoporosis occurs. Synthetic materials that intrinsically stimulate bone formation without inclusion of exogenous cells or growth factors represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Herein, we developed a series of hydroxyapatite bioceramics composed of a microwhiskered scaffold (wHA) reinforced with multiple layers of releasable hydroxyapatite nanoparticles (nHA). These novel bioceramics (nwHA) are tunable to optimize the loading amount of nHA for osteoporotic bone formation. The utility of nwHA bioceramics for the proliferation or differentiation of osteoporotic osteoblasts in vitro is demonstrated. A much more compelling response is seen when bioceramics are implanted in critical-sized femur defects in osteoporotic rats, as nwHA bioceramics promote significantly higher bone regeneration and delay adjacent bone loss. Moreover, the nwHA bioceramics loaded with a moderate amount of nHA can induce new bone formation with a higher degree of ossification and homogenization. Two types of osteogenesis inside the nwHA bioceramic pores were discovered for the first time, depending on the direction of growth of the new bone. The current study recommends that these tailored hybrid micro/nanostructured bioceramics represent promising candidates for osteoporotic bone repair.

Mineralized collagen-modified PMMA cement enhances bone integration and reduces fibrous encapsulation in the treatment of lumbar degenerative disc disease.

As a minimally invasive surgery, percutaneous cement discoplasty (PCD) is now contemplated to treat lumbar disc degeneration disease in elder population. Here, we investigated whether the osteogenic mineralized collagen (MC) modified polymethylmethacrylate (PMMA) cement could be a suitable material in PCD surgery. Injectability, hydrophilicity and mechanical properties of the MC-modified PMMA (PMMA-MC) was characterized. The introduction of MC did not change the application and setting time of PMMA and was easy to be handled in minimally invasive operation. Hydrophilicity of PMMA-MC was greatly improved and its elastic modulus was tailored to complement mechanical performance of bone under dynamic stress. Then, PCD surgery in a goat model with induced disc degeneration was performed with implantation of PMMA-MC or PMMA. Three months after implantation, micro-computed tomography analysis revealed a 36.4% higher circumferential contact index between PMMA-MC and bone, as compared to PMMA alone. Histological staining confirmed that the surface of PMMA-MC was in direct contact with new bone, while the PMMA was covered by fibrous tissue. The observed gathering of macrophages around the implant was suspected to be the cause of fibrous encapsulation. Therefore, the interactions of PMMA and PMMA-MC with macrophages were investigated in vitro. We discovered that the addition of MC could hinder the proliferation and fusion of the macrophages. Moreover, expressions of fibroblast-stimulating growth factors, insulin-like growth factor, basic fibroblast growth factor and tumor necrosis factor-ß were significantly down-regulated in the macrophages cocultured with PMMA-MC. Together, the promoted osteointegration and reduced fibrous tissue formation observed with PMMA-MC material makes it a promising candidate for PCD surgery.

Complexation of Injectable Biphasic Calcium Phosphate with Phosphoserine-Presenting Dendrons with Enhanced Osteoregenerative Properties.

Injectable biphasic calcium phosphates have been proposed as a solution in the treatment of a range of clinical applications including as fillers in the augmentation of osteoporotic bone. To date, various biodegradable natural or synthetic organics have been used as a polymer component of bone materials to increase their cohesiveness. Herein, a novel bone material was developed combining osteoconductive biphasic calcium phosphate (BCP) nanoparticles with phosphoserine-tethered generation 3 poly(epsilon-lysine) dendron (G3-K PS), a class of hyperbranched peptides previously shown to induce biomineralization and stem cell osteogenic differentiation. Strontium was also incorporated into the BCP nanocrystals (SrBCP) to prevent bone resorption. Within 24 h, an antiwashout behavior was observed in G3-K PS-integrated pure BCP group (BCPG3). Moreover, both in vitro tests by relevant cell phenotypes and an in vivo tissue regeneration study by an osteoporotic animal bone implantation showed that the integration of G3-K PS would downregulate Cxcl9 gene and protein expressions, thus enhancing bone regeneration measured as bone mineral density, new bone volume ratio, and trabecular microarchitectural parameters. However, no synergistic effect was found when Sr was incorporated into the BCPG3 bone pastes. Notably, results indicated a concomitant reduction of bone regeneration potential assessed as reduced Runx2 and PINP expression when bone resorptive RANKL and CTX-I levels were reduced by Sr supplementation. Altogether, the results suggest the potential of injectable BCPG3 bone materials in the treatment of osteoporotic bone defects.