Large-area alginate/PEO-PPO-PEO hydrogels with thermoreversible rheology at physiological temperatures

Alginate hydrogels have shown great promise for applications in wound dressings, drug delivery, and tissue engineering. Here, we report the fabrication, rheological properties, and dynamics of a multicomponent hydrogel consisting of alginate and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, and the achievement of thick, castable gels with tunable, thermoreversible behavior at physiological temperatures (Figure 1). PEO-PPO-PEO triblock copolymers can form temperature-sensitive hydrogels that exist as liquids at low temperatures and soft solids at high temperatures. In this work, we have employed PEO-PPO-PEO triblock copolymers to impart thermoresponsive properties to alginate hydrogels in the form of a multicomponent hydrogel. These systems can transition between a weak gel and a stiff gel, with a corresponding increase in the viscoelastic moduli of approximately two orders of magnitude as temperature is increased. The temperatures corresponding to the upper and lower boundaries of the stiff gel region, as well as the storage modulus at physiological temperatures (e.g., 36 – 40 C), can be controlled through the PEO-PPO- PEO concentration. Additionally, we explore the properties of these materials under compression and large deformations, and describe how alginate and F127 concentration can be used to control the fracture stress and strain. Finally, we compare the results from bulk rheology to the structure and dynamics of the gels measured via small-angle X-ray scattering (SAXS) and X-ray photon correlation spectroscopy (XPCS) experiments. Please click Additional Files below to see the full abstract

Can softer junctions lead to stiffer gels? Understanding the role of stereochemistry in associative polymer gels

The ability to create synthetic materials that mimic the structural and mechanical properties of soft biological tissues remains a significant challenge. In this presentation, we focus on creating stiff hydrogels and novel nanoscale and microscale structure by engineering crystalline domains into associative hydrogels of poly(lactic acid)-poly(ethylene oxide)-poly(lactic acid) (PLA-PEO-PLA) triblock copolymers. In aqueous media, these materials form associative gels of micelles with PLA cores that serve as network junctions. We extend previous studies from our group and others by varying the stereochemistry of the PLA block to create polymers with PLA blocks with ratios of L/D lactide units varying from 100/0 to 50/50. We had previously found that the 100/0 systems (triblocks with poly(L-lactide) blocks) formed gels with nanoscale crystalline domains, and these gels displayed a high value of the elastic modulus which was strongly dependent on PLA block length. Interestingly, our most recent results show that the storage modulus of these gels does not vary monotonically with L/D ratio. Rather, systems at intermediate L/D values are stiffer than the 100/0 systems, displaying higher storage moduli in spite of the fact that the PLA domains are expected to have a lower degree of crystallinity than in the 100/0 systems. Small-angle neutron scattering (SANS) results also indicate that the strongest interactions between micelles occurs for systems with intermediate L/D ratios, and ultra-small angle neutron scattering (USANS) shows evidence of larger structures in these gels, reminiscent of the hierarchical structures observed in biological gels. Collectively, our work shows that stereochemistry can be used in unexpected ways to access novel structures and properties in relatively simple synthetic polymers, giving insight into new routes for creating complex soft materials

Softer Junctions Can Result In Stiffer Gels: Associative Polymer Gels With Crystalline And Semicrystalline Domains

The ability to create synthetic materials that mimic the structural and mechanical properties of soft biological tissues remains a significant challenge. In this presentation, we discuss rheology and structural studies of poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) triblock copolymer gels with various ratios of L-lactide and D-lactide in the PLA blocks (Figure 1). These materials form associative micellar gels in water, and previous work has shown that stereoregular triblocks with a L/D ratio of 100/0 form much stiffer gels than triblocks with a 50/50 L/D ratio. Our systems display an unexpected maximum in the storage modulus, G’, of the hydrogels at intermediate L/D ratio. The impact of stereochemistry on the rheology is very striking; gels with an L/D ratio of 85/15 have storage moduli that are ~1-2 orders of magnitude higher than hydrogels with L/D ratios of 100/0. No stereocomplexation is observed in the gels, although PLLA crystals are found for gels with L/D ratios of 95/5 and 90/10, and SANS results show a decrease in the intermicellar spacing for intermediate L/D ratios. We expect the dominant contribution to the elasticity of the gels to be intermicellar brdging chains and attribute the rheology to a competition between an increase in the time for PLA endblocks to pull out of micelles as the L/D ratio is increased and PLLA crystallization occurs, and a decrease in the number of bridging chains for micelles with crystalline PLA domains, as formation of bridges may be hindered by crowded crystalline PLA domains. Ultra-small angle neutron scattering (USANS) and confocal microscopy shows evidence of larger structures in these gels, reminiscent of the hierarchical structures observed in biological gels. These results provide a new strategy for controlling the rheology of PLA-based hydrogels for potential applications in biomaterials, as well as fundamental insights into how intermicellar interactions can be tuned via stereochemistry. Collectively, our work shows that stereochemistry can be used in unexpected ways to access novel structures and properties in relatively simple synthetic polymers, giving insight into new routes for creating complex soft materials. Please click Additional Files below to see the full abstract