Silk Fibroin Microparticle Scaffold for Use in Bone Void Filling: Safety and Efficacy Studies.

Silk fibroin (SF) is a natural biocompatible protein polymer extracted from cocoons of silkworm Bombyx mori. SF can be processed into a variety of different forms and shapes that can be used as scaffolds to support bone regeneration. Three-dimensional (3D) SF scaffolds have shown promise in bone-void-filling applications. In in vitro studies, it has been demonstrated that a microparticle-based SF (M-RSF) scaffold promotes the differentiation of stem cells into an osteoblastic lineage. The expression of differentiation markers was also significantly higher for M-RSF scaffolds as compared to other SF scaffolds and commercial ceramic scaffolds. In this work, we have evaluated the in vitro and in vivo biocompatibility of M-RSF scaffolds as per the ISO 10993 guidelines in a Good Laboratory Practice (GLP)-certified facility. The cytotoxicity, immunogenicity, genotoxicity, systemic toxicity, and implantation studies confirmed that the M-RSF scaffold is biocompatible. Further, the performance of the M-RSF scaffold to support bone formation was evaluated in in vivo bone implantation studies in a rabbit model. Calcium sulfate (CaSO4) scaffolds were chosen as reference material for this study as they are one of the preferred materials for bone-void-filling applications. M-RSF scaffold implantation sites showed a higher number of osteoblast and osteoclast cells as compared to CaSO4 implantation sites indicating active bone remodeling. The number density of osteocytes was double for M-RSF scaffold implantation sites, and these M-RSF scaffold implantation sites were characterized by enhanced collagen deposition, pointing toward a finer quality of the new bone formed. Moreover, the M-RSF scaffold implantation sites had a negligible incidence of secondary fractures as compared to the CaSO4 implantation sites (∼50% sites with secondary fracture), implying a reduction in postsurgical complications. Thus, the study demonstrates that the M-RSF scaffold is nontoxic for bone-void-filling applications and facilitates superior healing of fracture defects as compared to commercial calcium-based bone void fillers.

Microbes, intestinal inflammation and probiotics.

Inflammatory bowel disease (IBD) is known for causing disturbed homeostatic balance among the intestinal immune compartment, epithelium and microbiota. Owing to the emergence of IBD as a major cause of morbidity and mortality, great efforts have been put into understanding the sequence of intestinal inflammatory events. Intestinal macrophages and dendritic cells act in a synergistic fashion with intestinal epithelial cells and microbiota to initiate the triad that governs the intestinal immune responses (whether inflammatory or regulatory). In this review, we will discuss the interplay of intestinal epithelial cells, bacteria and the innate immune component. Moreover, whether or not genetic intervention of probiotic bacteria is a valid approach for attenuating/mitigating exaggerated inflammation and IBD will also be discussed.

Comparison of internal bone transport and vascularized fibular grafting for femoral bone defects.

OBJECTIVE: To compare results between vascularized fibular grafting and internal bone transport for large bone defects of the femur. DESIGN: Retrospective review of patients. SETTING: University teaching hospitals. PATIENTS: This study included 37 patients with femoral bone loss: 20 patients were treated with internal bone transport and seventeen patients were treated with vascularized fibular grafting. MAIN OUTCOME MEASUREMENTS: The outcomes investigated were external fixation time, external fixation index, bone results (union, infection, deformity, leg length discrepancy), and functional results. RESULTS: The mean amount of filled defect was 8.4 cm with internal bone transport and 8.9 cm with vascularized fibular grafting. The external fixation index was 1.4 months/cm with internal bone transport and 1 month/cm with vascularized fibular grafting. The bone results and functional results of the internal bone transport were excellent in 65% and 0%, good in 5% and 45%, fair in 5% and 40%, poor in 25% and 15%, respectively, whereas those of the vascularized fibular grafting were excellent in 35% and 0%, good in 25% and 47%, fair in 5% and 35%, and poor in 35% and 18%. CONCLUSION: With vascularized fibular grafting, careful monitoring of circulation and early intervention surgery is necessary to avoid vascular failure. With internal bone transport, repeated radical debridement until control of infection is achieved, bone grafting at the docking site for early union, and avoiding stress fracture are recommended to improve bone results.