Comparison between heparin-conjugated fibrin and collagen sponge as bone morphogenetic protein-2 carriers for bone regeneration

Abstract

Bone morphogenetic protein-2 (BMP-2) is used to promote bone regeneration. However, the bone regeneration ability of BMP-2 relies heavily on the delivery vehicle. Previously, we have developed heparin-conjugated fibrin (HCF), a vehicle for long-term delivery of BMP-2 and demonstrated that long-term delivery of BMP-2 enhanced its osteogenic efficacy as compared to short-term delivery at an equivalent dose. The aim of this study was to compare the bone-forming ability of the BMP-2 delivered by HCF to that delivered by clinically utilized BMP-2 delivery vehicle collagen sponge. An in vitro release profile of BMP-2 showed that HCF released 80% of the loaded BMP-2 within 20 days, whereas collagen sponge released the same amount within the first 6 days. Moreover, the BMP-2 released from the HCF showed significantly higher alkaline phosphatase activity than the BMP-2 released from collagen sponge at 2 weeks in vitro. Various doses of BMP-2 were delivered with HCF or collagen sponge to mouse calvarial defects. Eight weeks after the treatment, bone regeneration was evaluated by computed tomography, histology, and histomorphometric analysis. The dose of BMP-2 delivered by HCF to achieve 100% bone formation in the defects was less than half of the BMP-2 dose delivered by collagen sponge to achieve a similar level of bone formation. Additionally, bone regenerated by the HCF-BMP-2 had higher bone density than bone regenerated by the collagen sponge-BMP-2. These data demonstrate that HCF as a BMP-2 delivery vehicle exerts better osteogenic ability of BMP-2 than collagen sponge, a clinically utilized delivery vehicle.

In situ hybridization of carbon nanotubes with bacterial cellulose for three-dimensional hybrid bioscaffolds

“…To evaluate the in vivo performance of CNT-BC-Syn, it was applied as a bone graft for bone regeneration application, and the results were compared with those obtained by using BC, CNT-BCImm, and collagen sponge loaded with bone morphogenetic protein-2 (Col-BMP-2), a clinically used bone graft [28]. The microscopic computed tomographic (micro-CT) analyses performed 8 weeks after the implantation of the scaffolds into the critical-sized defect in mouse calvaria showed a similar bone regeneration efficacy of CNT-BC-Syn, and Col-BMP-2, which was much higher than that of BC or CNT-BC-Imm (Fig.…”

Combination of BMP2 and MSCs Significantly Increases Bone Formation in the Rat Arterio-Venous Loop Model

“…Although Yang et al were able to show a prolonged release period of BMP2 in vitro and an increased in vivo bone generation using HCF immobilized BMP2 compared to collagen sponges, we were not able to verify these observations in our in vivo subcutaneous model. 17,18 With respect to bone generation, we used a BMP2 concentration of 60 mg/mL in this study. Clinically, the current FDA-approved BMP2 concentration is 1.5 mg/mL often combined with collagen sponges as the release system.…”

Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels

“…Although the osteoinductive effect of BMP-2 has been demonstrated in a wide variety of species (including rats, rabbits, dogs, sheep and non-human primates) (An and Friedman, 1999), it is often argued that one must be cautious in assuming that stromal cells from other species may serve as models for inducible osteogenesis in human marrow stromal cells (Diefenderfer et al, 2003). BMP-induced side effects, including cyst-like bone formation and soft tissue swelling, are likely caused by supra-physiological dosages used in humans (Carragee et al, 2011) and these adverse effects were recently reproduced in a similar in vivo model as used in this study with BMP-2 concentrations exceeding 20 µg per defect (Angle et al, 2012;Zara et al, 2011). In contrast, a dose between 2.5 and 10 µg was found to be safe and effective for various other BMP release systems including alginate-based (Boerckel et al, 2011), poly-Llactic acid (PLLA)-based (Wei et al, 2007) or silk-based (Bessa et al, 2010) scaffolds.…”