Surface Modification Of PEG Hydrogels By Gold Microarrays And Corresponding Studies Of Cell Adhesion On The Patterned Surface

Recent development of regenerative medicine including tissue engineering triggers research of surface modification of biomaterials and cell adhesion on modified substrate. Considering that tissues could be thought as a composite of cells and extracellular matrix (ECM), ideal biomaterials for tissue regeneration are desired to mimic ECM. Development of the new-generation biomaterials requires extensive understanding of cell-material interaction. Surface-patterning techniques shed light on simplifying the understanding of fundamental investigation in the cost of complicated material fabrication. The surface patterning techniques so far are, however, limited to hard substrates or some hydrophobic rubber such as silicone; on the other hand, hydrogels as a soft matter have emerged as a hot issue in material studies. Hence, a surface-patterning technique platform for generating patterns with cell-adhesion contrast on hydrogels is called for.This paper introduces a photolithography transfer strategy which can modify poly(ethylene glycol) (PEG) hydrogel by Au microarrays. The micropatterned biomaterial has cell-adhesion contrast, which can regulate cell adhesion and be used to study cell-biomaterial interactions. The fundamental studies might be helpful for the development of novel biomaterials.The main achievements are summarized as follows:1. To suggest a transfer strategy to fabricate stable micropatterns on hydrogels. The coupling of photolithography and microtransfer techniques is used to fabricate Au microarrays on PEG hydrogel surface, which resolves a problem of patterned modification of soft materials. Firstly, gold microarray is prepared on a hard inorganic substrate by the conventionally photolithography technique. Then, a thiol-end macromolecular linker is linked to gold micropattern and transferred to a polymeric substrate in photopolymerization of PEG-DA macromonomers. The resultant patterns are confirmed to keep stability even in water.2. To design a hetero-bifunctional macromolecular linker, and perform successfully the synthesis after overcoming an "inherent" difficulty of reaction between the two end groups. A well-designed hetero-bifunctional macromonomer linker, ACRL-PEG5K-SH, is synthesized and successful used to prepare gold microarrays onto a PEG hydrogel surface. The disulfide model is used to prevent the Michael addition between -SH and ACRL groups and other side reactions. Cell experiments confirm the biocompatibility and cell-adhesion contrast of the resulting patterned hydrogel. The adhesion of cells exhibits dependence of microdot sizes.3. To put forward a series of parameter to semi-quantified cell orientation on stripe-patterned surfaces. We further prepared, by the photolithography transfer technique, stable gold (Au) micropattems on PEG hydrogel surfaces with defined cell-resistant (PEG hydrogel) and cell-adhesive (gold microstripes) properties. 3T3 fibroblasts were cultured on Au-microstripe surfaces to observe cell adhesion and orientation. Five statistical parameters were defined and used to describe cell orientation on micropattems. The abrupt changes of these parameters did not happen at the same inter-distance. The combination of the 5 statistical parameters represented well the cell orientation behaviors semi-quantitatively.