Sarvesh K. Agrawal

Nanoparticle-Reinforced Associative Network Hydrogels

ABA triblock copolymers in solvents selective for the midblock are known to form associative micellar gels. We have modified the structure and rheology of ABA triblock copolymer gels comprising poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) through addition of a clay nanoparticle, laponite. Addition of laponite particles resulted in additional junction points in the gel via adsorption of the PEO corona chains onto the clay surfaces. Rheological measurements showed that this strategy led to a significant enhancement of the gel elastic modulus with small amounts of nanoparticles. Further characterization using small-angle X-ray scattering and dynamic light scattering confirmed that nanoparticles increase the intermicellar attraction and result in aggregation of PLA-PEO-PLA micelles.

New properties from PLA–PEO–PLA hydrogels

Polymeric materials are important in many medical applications. Regenerative medicine offers the potential to repair or replace damaged tissue and polymers are an essential component of many tissue engineering approaches. Hydrogels have many advantageous properties but, generally, lack robust mechanical properties. At the same time, mounting evidence points to the importance of the matrix modulus when constructing devices. In this context, triblock copolymers made from poly(-lactide)-poly(ethylene glycol)-poly(-lactide) have been prepared and formulated into hydrogels. Investigations into their mechanical properties found the elastic modulus to be greater than 10 kPa which is at least one order of magnitude stiffer than previously reported from macromolecules composed of similar monomers. Part of the reason is the presence of crystalline lactide domains. Creating hydrogels with tailored modulus across the kPa range will likely have important ramifications in regenerative medicine.

Energetics of association in poly(lactic acid)-based hydrogels with crystalline and nanoparticle-polymer junctions.

We report the energetics of association in polymeric gels with two types of junction points: crystalline hydrophobic junctions and polymer-nanoparticle junctions. Time-temperature superposition (TTS) of small-amplitude oscillatory rheological measurements was used to probe crystalline poly(L-lactide) (PLLA)-based gels with and without added laponite nanoparticles. For associative polymer gels, the activation energy derived from the TTS shift factors is generally accepted as the associative strength or energy needed to break a junction point. Our systems were found to obey TTS over a wide temperature range of 15-70 °C. For systems with no added nanoparticles, two distinct behaviors were seen, with a transition occurring at a temperature close to the glass transition temperature of PLLA, T(g). Above T(g), the activation energy was similar to the PLLA crystallization enthalpy, suggesting that the activation energy is related to the energy needed to pull a PLLA chain out of the crystalline domain. Below T(g), the activation energy is expected to be the energy required to increase mobility of the polymer chains and soften the glassy regions of the PLLA core. Similar behavior was seen in the nanocomposite gels with added laponite; however, the added clay appears to reduce the average value of the activation enthalpy. This confirms our SAXS results and suggests that laponite particles are participating in the network structure.

Micro- to Nano-scale Structure and Drug Release Behavior of Solutions and Hydrogels of Poly (lactide)-Poly (ethylene oxide)-Poly (lactide) Triblock Copolymers

We have performed for the first time a complete structural characterization of PLA-PEO-PLA in the solution and hydrogel states. Previous studies on hydrogels of these polymers have shown that these gels have excellent mechanical properties suitable for possible application in tissue engineering and drug delivery. We have performed SANS, USAXS and confocal microscopy to relate the change in micro to nano scale self-assembled structure of these polymers in aqueous solution with changes in the block length and stereospecificity of the PLA block. A significant difference in structure and association behavior was seen between the polymers made from amorphous D/L-lactide as compared to those with crystalline L lactide blocks. In the former case spherical micelles were seen to form whereas the latter forms nonspherical polydisperse micellar assemblies. Both polymers form an associative network structure at higher concentrations, leading to gelation. USAXS and confocal microscopy show the presence of large-scale fractal aggregates in the hydrogels of these polymers. The fractal structure was denser for the L lactide series polymers as compared to the D/L-lactide series polymers. These results show that we can tune the microstructure and thereby the mechanical strength of these gels depending upon the specific application we need it for. We also show profiles for release of hydrophobic drug sulindac from 5 weight% solutions of these polymers in phosphate buffer saline. The profiles follows an almost zero order release behavior that continues slowly and steadily over several days and is again found to be strongly dependent on the crystallinity and molecular weight of the PLA block.