Chemical And Morphological Variation Of Poly(Ester Amide) Synthesis And Fabrication And Their Use In Mast Cell Stabilization And Wound Healing

Abstract

Based on their unqiue chemical and mechanical properties, amino acid-based poly(ester amide) polymers (AA-PEAs) have demonstrated excellent performance for utility in biomedical devices. Owning to their chemical composition, AA-PEAs underwent hydrolytic and enzymatic degradation to facilitate both in vitro and in vivo biodegradation. Variations in the amino acid incorporated in monomer synthesis altered polymer characterisitics such as hydrophobicity (L-Phenylalanine) and Hydrophilicity/surface charge (L-Arginine). Attibuted to the bioanalogous pseudo-protein compostion of AA-PEAs, these polymers have shown low cytotoxicity, low proinflammatory cytokine production, and excellent cell adhesion. Therefore, these polymers are an excellent platform to which biomedical device and drug delivery systems can be built. Variable techniques in polymer fabrication offered an expanded field of AA-PEA function. Hydrophobic AA-PEAs were fabricated into 2D films and nano-scale 3D fibers with biomimetic function and hydrophilic AA-PEAs were incorporated into self-assembled microparticles and hydrogels. Hydrophobic films and fibers allowed for longer in vitro polymer retention, while hydrophilic AA-PEAs were utilized to integrate cationic charge into hybrid systems to improve cell/biomaterial interactions. In all cases, AA-PEAs alone or combined into a hybrid system offered equivalent mechanical performance with equal or better cell compatibility. i By examining which parameters of polymer composition (hydrophobicity, T g, morphology, surface charge) stimulate cellular response, a new generation of more funcational and biocompatibile devices can be fabricated. Both microparticles with reduced surface charge and hydrogels with cationic surface charge by addition of arginine-based AA-PEAs showed improved performance over their commercial counterpart. Similarly, incorporation of small molecules into hydrophobic AA-PEA polymer systems did not detrimentally affect cell compatibility, indicating these materials as excellent candidates for drug delivery. This work shows that although hydrophobicity and morphology may play a supporting role in cell response, surface charge dominates inflammatory response and cell adhesion. ii