Controlled multiple growth factor delivery from bone tissue engineering scaffolds via designed affinity.

It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release. We hypothesized that mineral coatings could be used as a platform for controlled incorporation and release of multiple growth factors. Specifically, mineral-coated scaffolds were "dip coated" in multiple growth factor solutions, and growth factor binding and release were dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate (ß-TCP) scaffolds were fabricated using indirect solid-free form fabrication techniques and coated with a thin conformal mineral layer. Mineral-coated ß-TCP scaffolds were sequentially dipped in recombinant human vascular endothelial growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral-binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for the incorporation of each growth factor. The dual release profile showed sustained release of both growth factors for over more than 60 days. Scaffolds releasing either rhVEGF alone or the combination of growth factors showed an increase in blood vessel ingrowth in a dose-dependent manner in a sheep intramuscular implantation model. This approach demonstrates a "modular design" approach, in which a controllable biologics carrier is integrated into a structural scaffold as a thin surface coating.

Experimental and computational characterization of designed and fabricated 50:50 PLGA porous scaffolds for human trabecular bone applications.

The present study utilizes image-based computational methods and indirect solid freeform fabrication (SFF) technique to design and fabricate porous scaffolds, and then computationally estimates their elastic modulus and yield stress with experimental validation. 50:50 Poly (lactide-co-glycolide acid) (50:50 PLGA) porous scaffolds were designed using an image-based design technique, fabricated using indirect SFF technique, and characterized using micro-computed tomography (micro-CT) and mechanical testing. Micro-CT data was further used to non-destructively predict the scaffold elastic moduli and yield stress using a voxel-based finite element (FE) method, a technique that could find application in eventual scaffold quality control. Micro-CT data analysis confirmed that the fabricated scaffolds had controlled pore sizes, orthogonally interconnected pores and porosities which were identical to those of the designed files. Mechanical tests revealed that the compressive modulus and yield stresses were in the range of human trabecular bone. The results of FE analysis showed potential stress concentrations inside of the fabricated scaffold due to fabrication defects. Furthermore, the predicted moduli and yield stresses of the FE analysis showed strong correlations with those of the experiments. In the present study, we successfully fabricated scaffolds with designed architectures as well as predicted their mechanical properties in a nondestructive manner.

Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in an articular fracture model.

In articular fractures, both bone and cartilage are injured. We tested whether stem cells transduced with bone morphogenetic protein 2 (BMP2) can promote bone and cartilage repair. Distal femoral articular osteotomies in nude rats were treated with stem cells, either wild-type or transduced with an adenoviral (Ad) BMP2. Cells were delivered in alginate (ALG) carrier or by direct injection in saline solution. Gene expression of these cells at the osteotomy site was confirmed by in vivo imaging. At day 14, only the group that received AdBMP2 stem cells by direct injection showed completely healed osteotomies, while other groups remained unhealed (P < 0.0003). In ALG groups, bone healing was impeded by the development of a chondroid mass, most pronounced in the AdBMP2 ALG group (P < 0.002). We were successful in achieving repair of both bone and cartilage in vivousing direct stem cell injection. Our data suggests that BMP2 augmentation might be critically important in achieving this effect.