Addition of β-Malic Acid-Containing Poly(ethylene glycol) Dimethacrylate To Form Biodegradable and Biocompatible Hydrogels

Abstract

Poly(malic acid) is water-soluble, functionalizable, and biodegradable, making it attractive as a precursor of hydrogels for biomedical applications. However, homopoly(malic acid), with p<i>K</i>_1/2 of 4.3, is too acidic for biocompatibility. To overcome the acidity, we have synthesized β-malic acid-containing poly(ethylene glycol) dimethacrylate (PEGMAc) with p<i>K</i>_a of 5.02. Solutions of methacrylated <i>O</i>-carboxymethylchitosan (OCMCS), PEGMAc, and poly(ethylene glycol) diacrylate (PEGDA; 7:7:86 and 6:20:74 (w/w/w)) in water (80%) have near neutral pHs (6.8−6.9). These solutions form firm hydrogels when photopolymerized. These are referred to as O7-PEGMAc7-B86 and O6-PEGMAc20-B74 (where the numerals refer to the weight content of each component, O is OCMCS and B is PEGDA added to make blend). The carboxyl groups in PEGMAc permit the surface grafting of hydrogels with Arg-Gly-Asp (RGD). The cytocompatibilities of smooth muscle cells (SMCs) on RGD-grafted hydrogels were studied. From the tetrazolium salt reduction assay, O6-PEGMAc20-B74 was found to have significantly better 10th day cytocompatibility compared to hydrogels containing lower or no PEGMAc. These gels degrade upon hydrolysis releasing malic acid, PEG and OCMCS. The increased cell compatibility of O6-PEGMAc20-B74 is possibly due to increased surface RGD content and near neutral pH even during biodegradation. Our novel PEGMAc-modified blends are a promising functionalizable biodegradable hydrogel precursor providing improved cell proliferation.