[Show abstract][Hide abstract] ABSTRACT: Bone defects and fracture nonunions remain a substantial challenge for clinicians. Grafting procedures are limited by insufficient volume and donor site morbidity. As an alternative, biomaterial scaffolds functionalized through incorporation of growth factors such as bone morphogenetic proteins (BMPs) have been developed and appear to regenerate the structure and function of damaged or degenerated skeletal tissue. OBJECTIVES/PURPOSES: Our objectives were therefore to determine whether: (1) the addition of heparin alone to collagen scaffolds sufficed to promote bone formation in vivo; (2) collagen-heparin scaffold improved BMP-mediated bone regeneration; and (3) precomplexed heparin and BMP-2 delivered on collagen scaffold could restore long bone biomechanical strength.
We created bilateral surgical defects in the femora of 20 rats and filled the defects with PCL scaffolds with one of five treatments: collagen matrix (n = 5), collagen/heparin matrix (n = 7), collagen matrix + BMP-2 (n = 9), collagen/heparin matrix + BMP-2 (n = 9), or collagen matrix + BMP-2/heparin complex (n = 9). Bone formation was observed with radiographs and micro-CT analysis and biomechanical testing was used to assess strength.
The addition of heparin alone to collagen did not promote bone ingrowth and the addition of heparin to collagen did not improve BMP-mediated bone regeneration. Delivery of precomplexed BMP-2 and heparin in a collagen matrix resulted in new bone formation with mechanical properties similar to those of intact bone.
Our findings suggest delivery of precomplexed BMP-2 and heparin may be an advantageous strategy for treatment of clinically challenging bone defects.
Clinical Orthopaedics and Related Research 08/2011; 469(11):3111-7. DOI:10.1007/s11999-011-2012-x · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sustained release systems have been developed for the use of growth factors in tissue engineering applications. However, many of these systems continue to have limitations associated with low loading efficiencies and reduced biological activity after release. In this paper, we utilized a lipid-based microtube system for the sustained release of BMP-2. The lipid microtubes were fabricated using a self-assembly method, in order to avoid the use of harsh organic solvents that may damage the protein. BMP-2 was loaded into the microtubes by rehydrating dried microtubes in the protein solution. The loading efficiency and release kinetics of BMP-2 in the microtubes were measured using in vitro immunoassays. Loading efficiency was found to be dependent on microtube concentration. The potential for this system to deliver biologically active BMP-2 was assessed using the alkaline phosphatase assay and von Kossa staining on human mesenchymal stem cell cultures. The results demonstrate that the lipid microtube system is able to provide sustained delivery of biologically active BMP-2 and thereby induce osteogenic differentiation.