Structure-property correlations in a combinatorial library of degradable biomaterials

A combinatorial library of degradable polyarylates was prepared. These polymers are A-B-type copolymers consisting of an alternating sequence of a diphenol and a diacid. The library was prepared by copolymerizing, in all possible combinations, 14 different tyrosine-derived diphenols and eight different aliphatic diacids, resulting in 8 x 14 = 112 distinct polymers. This approach (a) increases the number of available polymeric candidate materials for medical applications, and (b) facilitates the identification of correlations between polymer structure and glass transition temperature, air-water contact angle, mechanical properties, and fibroblast proliferation. The pendent chain and backbone structures were systematically varied by (a) simple homologative variations in the number of methylene groups, (b) substitution of oxygen for methylene groups, and (c) introduction of branched and aromatic structures. The polymers contained within the library exhibited incremental variations in Tg (from 2 degrees C to 91 degrees C) and air-water contact angle (from 64 degrees to 101 degrees ). Fibroblast proliferation (in vitro, serum-containing media) ranged from approximating that measured on tissue culture polystyrene to complete absence of proliferation. Generally, decreased proliferation correlated linearly with increased surface hydrophobicity, except in those polymers derived from oxygen-containing diacids in their backbone which were uniformly good growth substrates even if their surfaces were very hydrophobic. In a selected subgroup of polymers, tensile strength of thin solvent cast films ranged from about 6 to 45 MPa, while Young's modulus (stiffness) ranged from about 0.3 to 1.7 GPa. Combinatorial biomaterial libraries such as these tyrosine-derived polyarylates permit the systematic study of material-dependent biological responses and provide the medical device designer with the option to choose a suitable material from a library of related polymers that encompasses a broad range of properties.