Phase I study was intended and did demonstrate feasibility of developing synthetic polyester monofilament sutures as alternatives to surgical gut sutures (SGS) with preferred properties in term of initial mechanical properties, strength retention profile, and tissue reactivity. Phase I results showed that (1) polyaxial amorphous polymeric initiators can be end-grafted with glycolide to produce crystalline fiber- forming segmented copolyesters (SP) and (2) two SP-based monofilaments were identified as candidates for further development in Phase II. Although the compliance of these monofilaments was higher compared to dry SGS, they were stiffer than wet SGS. Hence, post-Phase I studies were pursued on other polyaxial fiber-forming compositions which can be used to prepare compliant monofilaments with a modulus of less than 100 Kpsi while remaining competitive with SGS in terms of other suture properties. And segmented polyaxial grafted polyesters (SPGs) having chains made of practically amorphous polytrimethylene carbonate core and highly segmented crystallizable terminal components based principally on glycolide and e-caprolactone were explored and shown to have more promising properties than the SPs. Hence, Phase II objective was revised to focus on the development of the SPG system primarily to produce compliant monofilament sutures as preferred alternatives to plain and chromic SGS. And, Phase II plans entail (1) optimization of two SPG systems selected in post-Phase I to choose one final system to produce preferred alternatives to plain and chromic SGS, with and without reliance on significant radiation-dose modulation of their properties; (2) completion of development and process validation studies on selected sutures based on the final SPG system; (3) completion of comparative in vitro and in vivo studies of SGS and their synthetic SPG-based alternatives (SGS-A); (4) initiation of safety, stability, and scale-up studies on SGS-A; (5) completing exploratory studies on other SPs and/or SPGs as preferred alternatives to certain absorbable commercial monofilaments; and (6) completing Phase III plans. ? ? ?
