Open pore biodegradable matrices formed with gas foaming

Engineering tissues utilizing biodegradable polymer matrices is a promising approach to the treatment of a number of diseases. However, processing techniques utilized to fabricate these matrices typically involve organic solvents and/or high temperatures. Here we describe a process for fabricating matrices without the use of organic solvents and/or elevated temperatures. Disks comprised of polymer [e.g., poly (D,L-lactic-co-glycolic acid)] and NaCl particles were compression molded at room temperature and subsequently allowed to equilibrate with high pressure CO2 gas (800 psi). Creation of a thermodynamic instability led to the nucleation and growth of gas pores in the polymer particles, resulting in the expansion of the polymer particles. The polymer particles fused to form a continuous matrix with entrapped salt particles. The NaCl particles subsequently were leached to yield macropores within the polymer matrix. The overall porosity and level of pore connectivity were regulated by the ratio of polymer/salt particles and the size of salt particles. Both the compressive modulus (159+/-130 kPa versus 289+/-25 kPa) and the tensile modulus (334+/-52 kPa versus 1100+/-236 kPa) of the matrices formed with this approach were significantly greater than those formed with a standard solvent casting/particulate leaching process. The utility of these matrices was demonstrated by engineering smooth muscle tissue in vitro with them. This novel process, a combination of high pressure gas foaming and particulate leaching techniques, allows one to fabricate matrices with a well controlled porosity and pore structure. This process avoids the potential negatives associated with the use of high temperatures and/or organic solvents in biomaterials processing.