A silk hydrogel-based delivery system of bone morphogenetic protein for the treatment of large bone defects

Abstract

The use of tissue grafting for the repair of large bone defects has numerous limitations including donor site morbidity and the risk of disease transmission. These limitations have prompted research efforts to investigate the effects of combining biomaterial scaffolds with biochemical cues to augment bone repair. The goal of this study was to use a critically-sized rat femoral segmental defect model to investigate the efficacy of a delivery system consisting of an electrospun polycaprolactone (PCL) nanofiber mesh tube with a silk fibroin hydrogel for local recombinant bone morphogenetic protein 2 (BMP-2) delivery. Bilateral 8 mm segmental femoral defects were formed in 13-week-old Sprague Dawley rats. Perforated electrospun PCL nanofiber mesh tubes were fitted into the adjacent native bone such that the lumen of the tubes contained the defect (Kolambkar et al., 2011b). Silk hydrogels with or without BMP-2 were injected into the defect. Bone regeneration was longitudinally assessed using 2D X-ray radiography and 3D microcomputed topography (µCT). Following sacrifice at 12 weeks after surgery, the extracted femurs were either subjected to biomechanical testing or assigned for histology. The results demonstrated that silk was an effective carrier for BMP-2. Compared to the delivery system without BMP-2, the delivery system that contained BMP-2 resulted in more bone formation (p < 0.05) at 4, 8, 12 weeks after surgery. Biomechanical properties were also significantly improved in the presence of BMP-2 (p < 0.05) and were comparable to age-matched intact femurs. Histological evaluation of the defect region indicated that the silk hydrogel have completely been degraded by the end of the study. Based on these results, we conclude that a BMP-2 delivery system consisting of an electrospun PCL nanofiber mesh tube with a silk hydrogel presents an effective strategy for functional repair of large bone defects.

Injectable silk-polyethylene glycol hydrogels

“…Benefiting from its high content of crystalline b-sheet structure, silk hydrogels degrade slower than most other types of hydrogels, including collagen, hyaluronic acid and alginate and, depending on the concentrations, degradation may take weeks to months [7,9,36]. PEG-silk hydrogels have similar structural and mechanical properties to sonication and pH-induced silk hydrogels, as indicated above, so that slow degradation of PEG-silk hydrogels after being injected subcutaneously in rats was expected.…”

“…Since no harmful solvents or compounds are used in these processes, the silk hydrogel is a useful carrier for encapsulating and delivering cells as well as bioactive molecules, towards tissue repairs or therapeutics. Pre-formed silk hydrogels prepared by low pH or sonication have been used to repair bone defects in previous studies [7][8][9] Encapsulation and proliferation of human mesenchymal stem cells (hMSCs) in silk hydrogels was achieved over 3 weeks when the gel concentration was lower than 4% (w/v) [4]. In a related study, immature chondrocytes encapsulated in sonication-induced silk hydrogels were used for cartilage tissue engineering [10].…”

Effect of Cell Origin and Timing of Delivery for Stem Cell-Based Bone Tissue Engineering Using Biologically Functionalized Hydrogels

“…Samples were placed in a custom holder for micro-CT scanning. Mineralized matrix composition of the constructs was determined using a VivaCT scanner (Scanco Medical 17,[36][37][38][39] This corresponds to a mineral density of approximately 380 mgHA/ cm 3 . The scans were segmented such that only bone inside the nanofiber mesh was included in the analysis.…”

Silk as a potential candidate for bone tissue engineering

“…In another study, the efficacy of using a silk hydrogel containing BMP-2 loaded on a PCL nanofiber mesh tube to repair large bone defects was evaluated. The results had shown that using the current structure can increase the BMP-2-mediated bone formation after 4, 8, and 12 weeks postimplantation [189]. We recently fabricated a bio-hybrid SF/calcium phosphate/PLGA nanostructure for the controlled delivery of vascular endothelial growth factor (VEGF) in order to improve bone regeneration [190].…”