Low-pressure foaming: A novel method for the fabrication of porous scaffolds for tissue engineering

Scaffolds for tissue engineering applications must incorporate porosity for optimal cell seeding, tissue ingrowth, and vascularization, but common fabrication methods for achieving porosity are incompatible with a variety of polymers, limiting widespread use. In this study, porous scaffolds consisting of poly(1,8-octanediol-co-citrate) (POC) containing hydroxyapatite nanocrystals (HA) were fabricated using low-pressure foaming (LPF). LPF is a novel method of fabricating an interconnected, porous scaffold with relative ease. LPF takes advantage of air bubbles that act as pore nucleation sites during a polymer mixing step. Vacuum is applied to expand the nucleation sites into interconnected pores that are stabilized through cross-linking. POC was combined with 20%, 40%, and 60% by weight HA, and the effect of increasing HA particle content on porosity, mechanical properties, and alkaline phosphatase (ALP) activity of human mesenchymal stem cells (hMSC) was evaluated. The effect of the prepolymer viscosity on porosity and the mechanical properties of POC with 40% by weight HA (POC-40HA) were also assessed. POC-40HA scaffolds were also implanted in an osteochondral defect of a rabbit model, and the explants were assessed at 6 weeks using histology. With increasing HA content, the pore size of POC-HA scaffolds can be varied (85 to 1,003 μm) and controlled to mimic the pore size of native trabecular bone. The compression modulus increased with greater HA content under dry conditions and were retained to a greater extent than with porous scaffolds fabricated using salt-leaching under wet conditions. Furthermore, all POC-HA scaffolds prepared using LPF supported hMSC attachment, and an increase in ALP activity correlated with an increase in HA content. An increase in the prepolymer viscosity resulted in increased compression modulus, greater distance between pores, and less porosity. After 6 weeks in vivo, cell and tissue infiltration was present throughout the scaffold. This study describes a novel method of creating porous osteoconductive POC scaffolds without the need for porogen leaching and provides the groundwork for applying LPF to other elastomers and composites.