(192c) CO2 Assisted Development of PCL-Gelatin Based Scaffolds for Biomedical Applications

Polymer based biomedical systems need biocompatible and biodegradable polymer based structured scaffold/drug release systems with incorporation of multiple biomolecules and controlled release. Polycaprolactone (PCL) is one of the most widely used synthetic biodegradable polymers with good mechanical properties and an extended degradation period. Gelatin gives a natural platform for better cell adhesion but it has poor mechanical properties.  PCL-gelatin blend shows improved chemical and mechanical properties along with better cell adhesion. High pressure CO₂ assisted plasticization of polymers has been used for development of biodegradable foams and incorporation of additives in polymers. PCL foams have been studied using supercritical CO₂. However infusion of biomolecules in the PCL has been explored only for subcritical CO₂ since supercritical CO₂ causes structural deformation of pure PCL. We have recently demonstrated that different compositions of PCL-gelatin bend can be swelled reversibly by subcritical as well as supercritical CO₂without loss of structural integrity.  

Pure PCL is swelled in the presence of CO₂. However pure gelatin is compressed by high pressure CO₂. Differential scanning calorimetry and weight loss study on pure gelatin confirmed water extraction from gelatin by CO₂ phase. In the PCL-gelatin blend, this simultaneous mass transfer of CO₂ and water in the blend stabilizes the structure in the presence of supercritical CO₂. As the degree of swelling of PCL is higher than extent of compression of gelatin, the blend shows overall increase in the volume in the presence of CO₂. This characteristic behavior of the blend allows supercritical CO­₂assisted processing of PCL-gelatin without compensating structural integrity. Impregnation and release study of dye has been studied for PCL-gelatin (50/50 by vol.) which shows linear release profile avoiding huge initial burst. We have also demonstrated infusion of multiple dyes on same scaffold with controlled release profile for individual dye.

If water is externally added to the system, mechanical stability of the blend is affected due to swelling of gelatin. In the presence of humidified CO₂, both PCL and gelatin phases of the blend swell. Due to loss of mechanical strength from gelatin phase, depressurization of humidified CO₂ results in foaming of the blend. Foamed scaffolds can be then infused with drugs/proteins using ‘dry’ high pressure CO₂without compromising porosity and structure of scaffold.

Solubility of water in the CO₂ can be controlled by manipulating operating conditions. Although humidified CO₂ affects the mechanical stability of the blend, controlled exposure to the water and slow depressurization results in higher degree of swelling of the blend than swelling under pure CO₂. This allows higher loading of an additive in the blend using modulated operating conditions of high pressure humidified CO₂. We have demonstrated impregnation and release of a dye using humidified CO₂ which shows higher loading of the dye as compared to the dry CO₂impregnation.