Macrochannels Affect Bone Tissue Engineering Scaffold Efficacy

Objective: Small volumes of bone tissue can be easily engineered using standard tissue engineering strategies, but it is difficult to produce a large osseous block. Conventional wisdom dictates that this is primarily due to the lack of sufficient nutrient supply in large scaffolds, although differences in oxygen partial pressure inside and outside the scaffold may also play a role. We hypothesized that such problems could be eliminated by designing directionally specific macrochannels into a bone engineering scaffold. Thus, the purpose of our study was to investigate the influence of the presence, and direction, of macrochannels on bone formation within a scaffold.

Methods: We employed a custom-modified three-phase, PLGA/calcium phosphate, biodegradable scaffold blocks (OsteoScaf™, TRT Inc, Toronto). The blocks (17x10x7 mm) were either whole (Group 1) or modified with one 2x17mm hole in (Group 2/, or three 2x7mm holes perpendicular to (Group 3), the scaffold long axis. Rat bone marrow cells were seeded in the scaffolds at a nominal concentration of 2x105 cells/cm2, and cultured in standard osteogenic conditions (aMEM, 10%FBS, 10-8M dexamethasone, 5mM b-glycerophosphate, 100mg L-ascorbic acid) for 2 weeks at 37°C/5% CO2. The cell/scaffold composites were implanted subcutaneously in the dorsum of SPF/VAN BALB/cAnNCrj-nu (nu/nu) nude mice. After 2, 4 and 8 weeks implantation, the specimens were harvested, fixed, decalcified, and paraffin embedded. Sections were stained with H-E.

Result: Group 1 showed bone formation only around scaffold. Group 2 showed good bone formation on the ventral side, but less on the dorsal (skin) side. On the contrary, Group 3 samples exhibited extensive bone formation throughout the scaffold. These results demonstrate that the vertical macrochannels, providing access to the blood supply from the dorsal musculature, provided the most efficient nutrient supply for the seeded osteogenic cells.

Conclusion: We demonstrated the necessity and efficacy of scaffold macrochannels to optimize bone formation.