Chemical and mechanical characterization of fully degradable double-network hydrogels based on PEG and PAA

Biodegradable polymer hydrogels have become very promising materials for use in tissue engineering. Hydrogels are typically used as scaffolds within which cells can be seeded for regeneration of damaged tissue. Ideally, these hydrogels should be easily implanted in the body in a minimally invasive manner, should be relatively highly swollen in order to allow adequate transport of nutrients, and should degrade safely in the body while new tissue is regenerated. Additionally, for optimal success, an increasing number of studies indicate that matching the mechanical properties of the hydrogel with those of the tissue being replaced is a significant factor. While a wide variety of hydrogels with a number of these individual properties exist, few hydrogels have a combination of all these properties. For instance, it is rare for hydrogels to have good mechanical properties at high swelling degrees, and few hydrogels with persistently good mechanical properties are also biodegradable and/or easily implanted in a non-invasive manner. This study seeks to combine a number of the qualities that make a hydrogel ideal for tissue engineering by investigating the development of a fully injectable and biodegradable hydrogel with enhanced mechanical properties that persist at high degrees of swelling.;More specifically, the goal of this research is to develop and investigate the swelling, mechanical and degradation properties of biodegradable hydrogels with potentially enhanced stiffness mechanical properties, with the fundamental components consisting of a complex-forming polymer pair of poly(ethylene glycol) (PEG) and poly(acrylic acid) (PAA). The hydrogels are synthesized with a specific interpenetrating polymer network (IPN) strategy, referred to as a double network (DN) strategy, that has been used to enhance the mechanical properties of a variety of non-degradable hydrogels but has only been applied to a few biodegradable hydrogels.;The biodegradable DNs were formed by adding degradable functionalities to the PEG and PAA network components. The biodegradable PEG component was prepared using an existing method, where ABA-type block copolymers were first synthesized in order to form poly(lactic acid)-b-ploy(ethylene glycol)-b-poly(lactic acid) (PLA-b-PEG- b- PLA) hydrogels with hydrolytically labile PLA units. Then, in order to make these copolymers photo-crosslinkable, the chain-ends of the copolymers were functionalized with acrylate groups to form di-acrylated PLA- b-PEG-b-PLA macromers. For experimental purposes, PEG molecular weights of 2000, 4000 and 8000 g/mol were used. The obtained macromers were then photo-polymerized in the presence of a photoinitiator to form biodegradable PLA-PEG-PLA hydrogels with molecular weight between crosslink (Mc) values that depended on the PEG molecular weight. Additionally, during preparation of the hydrogels, two different macromer concentrations (25% and 50%) were used for each PEG molecular weight to yield hydrogels with additional variations in Mc.;For the degradable PAA component, acrylic acid (AA) monomers were photopolymerized in the presence of a photoinitiator and a biodegradable crosslinker. The biodegradable crosslinker was made by synthesizing di-acrylated PLA-PEG-PLA macromers similar to the ones described above, but with a low PEG molecular weight of 600 g/mol. For photopolymerization of the PAA component with this crosslinker, a constant AA volume fraction of 0.8 was used with two different crosslinker concentrations (1% and 8%).;The degradable DN hydrogels were prepared using a sequential polymerization process with PLA-PEG-PLA as the 1st network and the PAA component as the 2nd network. The PLA-PEG-PLA hydrogels were photopolymerized and then swollen to equilibrium in AA monomer solutions for subsequent photopolymerization of the degradable PAA component within the PLA-PEG-PLA hydrogel. Single-network PLAPEG- PLA hydrogels and single-network PAA hydrogels (with biodegradable crosslinker) were also photopolymerized for comparison to the DNs. The chemical and structural characteristics of the obtained copolymers, macromers and networks were characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, gel permeation chromatography (GPC) and swelling measurements. For all of the hydrogels, swelling and degradation were characterized over various time periods through gravimetric measurements, the storage modulus was characterized over appropriate degradation periods using dynamic mechanical analysis (DMA), and the thermal behavior was characterized using differential scanning calorimetry (DSC).