Effect of Polycaprolactone Scaffold Permeability on Bone Regeneration In Vivo

Abstract

Successful bone tissue engineering depends on the scaffold's ability to allow nutrient diffusion to and waste removal from the regeneration site, as well as provide an appropriate mechanical environment. Since bone is highly vascularized, scaffolds that provide greater mass transport may support increased bone regeneration. Permeability encompasses the salient features of three-dimensional porous scaffold architecture effects on scaffold mass transport. We hypothesized that higher permeability scaffolds will enhance bone regeneration for a given cell seeding density. We manufactured poly-e-caprolactone scaffolds, designed to have the same internal pore design and either a low permeability (0.688 · 10 /N-s), respectively. Scaffolds were seeded with bone morphogenic protein-7-transduced human gingival fibroblasts and implanted subcutaneously in immune-compromised mice for 4 and 8 weeks. Micro-CT evaluation showed better bone penetration into high permeability scaffolds, with blood vessel infiltration visible at 4 weeks. Compression testing showed that scaffold design had more influence on elastic modulus than time point did and that bone tissue infiltration increased the mechanical properties of the high permeability scaffolds at 8 weeks. These results suggest that for polycaprolactone, a more permeable scaffold with regular architecture is best for in vivo bone regeneration. This finding is an important step toward the end goal of optimizing a scaffold for bone tissue engineering.

Fabrication, mechanical and in vivo performance of polycaprolactone/tricalcium phosphate composite scaffolds

“…Wiria et al [23] reported on the in vitro cell ingrowth of PCL/HA scaffolds fabricated via SLS, however, even though the success of the addition of a bioactive phase is anticipated, the in vivo performance of such composite scaffolds has not been extensively reported. Reports on in vivo testing of PCL based scaffolds fabricated by other rapid prototyping techniques are limited to small animal models [30][31][32][33][34][35][36].…”

Evaluation of a biomimetic poly(ε-caprolactone)/β-tricalcium phosphate multispiral scaffold for bone tissue engineering: In vitro and in vivo studies

“…32 In addition, cells should disperse homogenously throughout the surface. 33 When we switched to the osteogenic medium, MSCs with typical fibroblastoid morphology modified into osteogenic cells with strong matrix accumulation.…”

“…2,32,41 Percentage of porosity and the size of the pores are paramount in allowing migration of cells, which is necessary for successful osteoinduction and vascularization. Fiber sizes and correspondingly pore sizes in a construct are essential for cell attachment, proliferation, nutrient, gas and waste transfer, cell-cell communication, and infiltration of the cells into the scaffold.…”

“…Pore size and fiber density adjustments can also effect in vivo bone tissue formation. 32,42 The fibers should allow metabolite flow between pores of bioceramic, support vitality, proliferation, and differentiation, hence constituting areas where cells can easily migrate. 43,44 Also for cells, microenvironment must be familiar and similar to what is natural.…”

Effect of oxygen plasma etching on pore size-controlled 3D polycaprolactone scaffolds for enhancing the early new bone formation in rabbit calvaria

“…Others have concluded that scaffold porosity is important for cell delivery and sufficient diffusion of nutrients and waste into and out of the scaffold 26) . Many studies support or refute the requirement of specific pore sizes and shapes, strut/fiber diameters, interconnectivity, or porosities for optimal bone growth 27) .…”