R. Bakshi1, A. Hokugo1, S. Zhou1, K. Rezzadeh1, L. A. Segovia1, S. Stupp2, R. Jarrahy1 1University Of California – Los Angeles,Regenerative Bioengineering And Repair (REBAR) Laboratory, Division Of Plastic And Reconstructive Surgery, Department Of Surgery,Los Angeles, CA, USA 2Northwestern University,Simpson Querrey Institute For BioNanotechnology,Chicago, IL, USA
Introduction:
Bone morphongenic proteins (BMPs) have numerous applications in craniofacial surgery and play a central role in the development of regenerative therapies for bone reconstruction. Unfortunately, the broad applications of BMPs are limited by its side effect profile and high cost. Nanoscale peptide amphiphiles (PAs) are a novel biomaterial that can self-assemble into nanofibers. These PA gels have demonstrated the ability to function as a controlled release carrier of BMP-2 and support bone regeneration. In this study, we examined the effect of PA gels on in vitro osteogenic differentiation of bone marrow stromal cells (BMSCs) and in vivo bone regeneration in cranial defects.
Methods:
BMSCs were cultured and treated either with control media or media with BMP-2 and PAs. Quantitative RT-PCR of genes specifically related to osteogenesis was used to assess for osteogenic differentiation in vitro. To study the in vivo effects, cleft palates were created in rat maxilla. The defect was treated with one of the following: 1) collagen with BMP-2 (high dose), 2) collagen with BMP-2 (low dose) and PAs 3) collagen with inert vehicle (control) or 4) no treatment. After 8 weeks, the maxilla was harvested for radiographic analysis with micro-computed tomography and for histology.
Results:
BMSCs treated with BMP-2 with PAs had increased up-regulation of markers of osteogenesis demonstrating osteogenic differentiation. The cleft palate implanted with collagen sponge and low dose BMP-2 showed bone regeneration comparable to the collagen with high dose BMP-2.
Conclusion:
PAs with BMP-2 have the ability to induce osteogenic differentiation in BMSCs as demonstrated by these results. The in vivo and in vitro studies demonstrate the osteogenic capacity of PAs with BMP-2. This data may represent the use of PAs with low dose BMP-2 as a viable alternative to current uses of clinical BMP-2 in tissue engineering.