Engineering tissues utilizing biodegradable polymer matrices is a prom
ising approach to the treatment of a number of diseases. However, proc
essing techniques utilized to fabricate these matrices typically invol
ve organic solvents and/or high temperatures. Here we describe a proce
ss for fabricating matrices without the use of organic solvents and/or
elevated temperatures. Disks comprised of polymer [e.g., poly (D,L-la
ctic-co-glycolic acid)] and NaCl particles were compression molded at
room temperature and subsequently allowed to equilibrate with high pre
ssure CO2 gas (800 psi). Creation of a thermodynamic instability led t
o the nucleation and growth of gas pores in the polymer particles, res
ulting in the expansion of the polymer particles. The polymer particle
s fused to form a continuous matrix with entrapped salt particles. The
NaCl particles subsequently were leached to yield macropores within t
he 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 significantl
y greater than those formed with a standard solvent casting/particulat
e leaching process. The utility of these matrices was demonstrated by
engineering smooth muscle tissue in vitro with them. This novel proces
s, a combination of high pressure gas foaming and particulate leaching
techniques, allows one to fabricate matrices with a well controlled p
orosity and pore structure. This process avoids the potential negative
s associated with the use of high temperatures and/or organic solvents
in biomaterials processing. (C) 1998 John Wiley & Sons, Inc.