Hybrid hydrogels based on RAFT mediated poly(N-vinyl pyrrolidone)

[摘要] ENGLISH ABSTRACT: The goal of this study was to synthesize hybrid hydrogels via a chemical crosslinking mechanism through use of chain end functional poly(N-vinyl pyrrolidone)(PVP) withvarious topologies. The crosslinking chemistries should be benign in nature i.e. at physiological pH ranges and at 37 °C. The degradation products should be biologically tolerable and renal clearance should be possible (< 30 000 g/mol PVP0.PVP of various topologies, controlled molar mass and quantitative chain endfunctionality was obtained via Reversible Addition Fragmentation chain Transfer(RAFT) mediated polymerization (PDI = 1.1- 1.4).The synthesized polymers were chain end functionalized to introduce thiol oraldehyde moieties. Thiol chain ends were obtained through post polymerization modification of xanthate functional PVP with either aminolysis or reduction. The aldehyde moiety was obtained by post polymerization modification of xanthate endfunctional PVP with sequential hydrolysis and thermolysis.Thiol functional four arm star PVP was reacted with acrylate difunctionalpoly(ethylene glycol) (DIAC PEG) crosslinker under standard Michael addition conditions. In order to obtain thioether crosslinked hydrogels from tetra functional star PVP molecules it was found that a minimum thiol functionalization of 30% and a molar ratio of acrylate:thiol of 1:1.1 is required.The Schiff base reaction was used to synthesize imine or secondary amine (afterreduction) crosslinks with the lysine residues on either lysozyme or bovine serum albumin (BSA) or the primary amines of bis-(2-amino ethyl)amine). Hydrogels were obtained from aldehyde functionalized PVP molecules with a fraction of functional aldehyde chain ends of 0.88 for difunctional molecules and 0.50 for tetra functional star PVP molecules with lysozyme or BSA crosslinkers. The reaction rate wasfavoured by lowered pH (<6.0) and an optimum molar ratio of amine : aldehyde of 1:0.8.Hydrogels were analyzed by equilibrium swelling calculations to determine the molar mass between crosslinks and the estimated pore size. In both crosslinking systems the properties of the formed hydrogels were seen to be affected by molar ratio used and by the topology of the crosslinking agent.PVP BSA and PVP PEG hydrogels were tested for 24 h and 48 h cell viability by usingH9C2 myoblast cells. A concentration range of 0.25 x 10(2) to 0.01 g/mL was studied.Cell mortality was tested by Trypan blue staining and results were verified with MTT assay. A very low cell death precentage (<37%)was observed. Cells even appeared to experience a stimulatory effect after 48 h of exposure at low concentrations ofPVP PEG hydrogel treatments. The properties of the formed hydrogel could be tuned by the molar mass ratios of PVP and crosslinker. The functionality of the crosslinker directly affects the molar mass between crosslinks and thus indirectly the degradation profile.It was concluded that PVP molecules with various topologies, well-defined molar masses and chain end functionality could be obtained via RAFT mediated polymerization. Obtained polymers were successfully modified and crosslinked toobtain hydrogels with stoichiometrically tuneable properties i.e. initial swelling ratio,degradation time, molar mass between crosslinks. The hydrogels had very positive cell viability results that would definitely justify further research into these materials as 'tissue-mimetic materials.

[发布机构] Stellenbosch University