Open pore biodegradable matrices formed with gas foaming

Abstract

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 CO 2 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 poly-mer 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.

From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges

“…[337][338][339][340][341][342][343] It has been shown that this method allows open-pore structures to be produced, when polymer is preventively mixed with a porogen. [337][338][339][340][341][342][343] Mixture is then equilibrated with high-pressure CO 2 for at least 16 h. [337][338][339][340][341][342][343] Then, by rapidly decreasing pressure (2-to 3-min), CO 2 nucleates and expands, thus causing polymeric particles to fuse. [337][338][339][340][341][342][343] Porogens are successively leached out only for 24 h, to assure removal of salt crystals and retention of entrapped molecule loading.…”

“…[337][338][339][340][341][342][343] Porogens are successively leached out only for 24 h, to assure removal of salt crystals and retention of entrapped molecule loading. [337][338][339][340][341][342][343] It has also been shown that entrapped proteins and plasmid DNAs suffered only a minimal loss in activity. [337][338][339][340][341][342][343] Other gas foaming methods utilize mixtures of effervescent salts as porogens.…”

“…[337][338][339][340][341][342][343] It has also been shown that entrapped proteins and plasmid DNAs suffered only a minimal loss in activity. [337][338][339][340][341][342][343] Other gas foaming methods utilize mixtures of effervescent salts as porogens. 344,345 Accordingly, porous scaffolds (90% porosity; pore size 100-200 mm) have been obtained by mixing crystals of ammonium bicarbonate with an organic viscous solution of PLA or PLGA.…”

Scaffold Design for Tissue Engineering

“…Several methods have been developed to prepare these kinds of porous three-dimensional biodegradable scaffolds, including gas foaming, [63,64] fiber extrusion and bonding, [65] three-dimensional printing, [66] phase separation, [67 -69] emulsion freeze-drying, [70] and porogen leaching. [71,72] The gas-foaming technique uses high-pressure CO 2 gas processing.…”

“…To improve the pore structure, a combination technique of gas foaming and particulate leaching has been recently proposed. [64] Open-pore biodegradable scaffolds have been fabricated. Disks composed of biodegradable polymer and salt particulates are compression-molded at room temperature and subsequently allowed to equilibrate with high-pressure CO 2 gas.…”