A new peptide-based urethane polymer: synthesis, biodegradation, and potential to support cell growth in vitro

Abstract

A novel non-toxic biodegradable lysine-di-isocyanate (LDI)-based urethane polymer was developed for use in tissue engineering applications. This matrix was synthesized with highly purified LDI made from the lysine diethylester. The ethyl ester of LDI was polymerized with glycerol to form a prepolymer. LDI-glycerol prepolymer when reacted with water foamed with the liberation of CO 2 to provide a pliable spongy urethane polymer. The LDI-glycerol matrix degraded in aqueous solutions at 100, 37, 22, and 4°C at a rate of 27.7, 1.8, 0.8, and 0.1 mM per 10 days, respectively. Its thermal stability in water allowed its sterilization by autoclaving. The degradation of the LDI-glycerol polymer yielded lysine, ethanol, and glycerol as breakdown products. The degradation products of LDI-glycerol polymer did not significantly affect the pH of the solution. The glass transition temperature (T g ) of this polymer was found to be 103.4°C. The physical properties of the polymer network were found to be adequate to support the cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSC) attached to the polymer matrix and remained viable on its surface. Culture of BMSC on LDI-glycerol matrix for long durations resulted in the formation of multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, cells grown on LDI-glycerol matrix did not differ phenotypically from the cells grown on the tissue culture polystyrene plates as assessed by the cell growth, and expression of mRNA for collagen type I, and transforming growth factor-β1 (TGF-β1). The observations suggest that biodegradable peptide-based urethane polymers can be synthesized which may pave their way for possible use in tissue engineering applications.

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

“…Polyurethane scaffolds synthesized from aliphatic and lysine-derived polyisocyanates have been reported to support cell attachment and proliferation in vitro, as well as ingrowth of new tissue and degradation to non-cytotoxic decomposition products in vivo (23,(37)(38)(39).…”

“…Hydrolysis of this ester group yields a carboxylic acid group in the polymer, which has been suggested to catalyze further degradation (47). For lysine-derived polyisocyanates, hydrolysis of urethane linkages to lysine has been reported, while others have reported that urethane and urea linkages are only enzymatically degraded (24,39,48). Higher soft segment content may also explain the faster degradation of the LTI materials, due to the higher %NCO (lower equivalent weight) of LTI relative to that of HDIt.…”

Biomimetic materials for tissue engineering

“…Progress has been made in the development of biodegradable PU or urethanebased polymers using less toxic diisocyanates [26]. These polymers have been explored for vascular and other tissue engineering applications [27][28][29].…”

Synthesis and structure-property relationships of biodegradable polyurethanes

“…FTIR spectroscopy showed an increase in hydrogen bonding as the hard segment length increased [114]. Some authors have reported that aliphatic BDI and LDI can degrade in the body to the diamine putrescine and amino acid lysine, respectively, which play an important role in cell growth and differentiation [115,116]. Guan et al [74] reported the synthesis of biodegradable PU and PUU copolymers based on PCL, BDI and a putrescine chain extender.…”