Matching tissue engineering scaffold modulus to that of native tissue is highly desirable. Effective scaffold modulus can be altered through changes in base material modulus and/or scaffold pore architecture. Because the latter may be restricted by tissue in-growth requirements, it is advantageous to be able to alter the base material modulus of a chosen scaffold material. Here, we show that the bulk modulus of poly(glycerol sebacate) (PGS) can be changed by varying molar ratios during prepolymer synthesis and by varying curing time. We go on to show that PGS can be used to create 3D designed scaffolds via solid freeform fabrication methods with modulus values that fall within the ranges of native articular cartilage equilibrium modulus. Furthermore, using base material modulus inputs, homogenization finite element analysis can effectively predict the tangent modulus of PGS scaffold designs, which provides a significant advantage for designing new cartilage regeneration scaffolds. Lastly, we demonstrate that this relatively new biomedical material supports cartilaginous matrix production by chondrocytes in vitro. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Bone tissue engineering scaffolds should be designed to optimize mass transport, cell migration, and mechanical integrity to facilitate and enhance new bone growth. Although many scaffold parameters could be modified to fulfill these requirements, pore size is an important scaffold characteristic that can be rigorously controlled with indirect solid freeform fabrication. We explored the effect of pore size on bone regeneration and scaffold mechanical properties using polycaprolactone (PCL) scaffolds designed with interconnected, cylindrical orthogonal pores. Three scaffold designs with unique microarchitectures were fabricated, having pore sizes of 350, 550, or 800 microm. Bone morphogenetic protein-7 transduced human gingival fibroblasts were suspended in fibrin gel, seeded into scaffolds, and implanted subcutaneously in immuno-compromised mice for 4 or 8 weeks. We found that (1) modulus and peak stress of the scaffold/bone constructs depended on pore size and porosity at 4 weeks but not at 8 weeks, (2) bone growth inside pores depended on pore size at 4 weeks but not at 8 weeks, and (3) the length of implantation time had a limited effect on scaffold/bone construct properties. In conclusion, pore sizes between 350 and 800 microm play a limited role in bone regeneration in this tissue engineering model. Therefore, it may be advantageous to explore the effects of other scaffold structural properties, such as pore shape, pore interconnectivity, or scaffold permeability, on bone regeneration when designing PCL scaffolds for bone tissue engineering.

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.

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Computationally designed scaffolds can support masticatory function in a large animal model as well as both osseous and cartilage regeneration. Our group is continuing to evaluate multiple implant designs in both young and mature Yucatan minipig animals.