Papers by Author: Andrew K. Whittaker

Abstract: A series of linear poly(2-hydroxyethyl methacrylate) (PHEMA) with defined molecular weights (MW) and narrow molecular distributions were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using cumyl dithiobenzoate (CDB) as a chain transfer agent. Murine fibroblasts (3T3) were exposed to eluates from various PHEMA samples, washed or unwashed, and with or without dithioester end groups. After 72 hrs in cell culture, no cytotoxic response was elicited by the polymer samples devoid of dithioester end groups, and which also underwent a thorough washing regime. Specimens throughout the entire MW range were internalized by a macrophage (cell line Raw 264), suggesting that such polymers can be used as models for studying the biodegradation of PHEMA.

Abstract: A nonapeptide, which is sensitive to enzymatic digestion by collagenase, was modified by the covalent attachment of an acrylamido group at the terminal positions. The functionalized peptide was used as a crosslinking agent during polymerization of 2-hydroxyethyl methacrylate (HEMA). Reversible addition-fragmentation chain transfer (RAFT) method was used to obtain a polymer (PHEMA) with an average theoretical molecular weight of 4000 Da, containing enzymatically labile peptide crosslinks. The functionalized peptide was analyzed in detail by 1H and 13C nuclear magnetic resonance (NMR) spectrometry. The polymerization reaction was monitored by near infrared spectrometry, while the resulting polymer was analyzed by size exclusion chromatography and solid NMR spectrometry. The peptide-crosslinked PHEMA was subjected to an in-vitro degradation assay in the presence of collagenase. At the highest concentration of enzyme used in the study, a weight loss of 35% was recorded after 60 days of incubation in the collagenolytic medium. This suggests that crosslinking with enzymatically degradable peptides is a valid method for inducing biodegradability in polymers that otherwise are not degradable.

Abstract: Cell-based therapy is one of the major potential therapeutic strategies for cardiovascular, neuronal and degenerative diseases in recent years. The aims of this study is to develop a novel biomimic polymeric materials which will facilitate the delivery cells, control cell bioactivities and enhance the focal integration of graft cells with host tissues. We synthesized a novel tri-block copolymer, methoxy-terminated poly (ethylene glycol) (MPEG)-polyL-lactide (PLLA)-polylysine (PLL) via sequential polymerization of PLLA onto MPEG, followed by ring opening polymerization of PLL onto the functionalized chain end. The triblock copolymer (5%) was then mixed with high molecular weight PLLA (95%) to form cell-delivery membranes. The spectra of copolymers were determined by NMR and ATR-FTIR spectroscopy. Human osteoblasts were used for testing biocompatibility and initial cellular reaction. It was noted that no cytotoxicity was detectable in our synthesized copolymers. Compared with pure PLLA and diblock copolymers, the triblock copolymers showed significantly better cell adhesion and proliferation. Interestingly we identified that cellular activity (attachment, proliferation and differentiation) could be regulated by the molecular weight and composition of the triblock copolymers. In conclusion controllable synthetic copolymers can be designed and synthesized to modulate cellular function in facilitating tissue repair and regeneration.