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.

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.

Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks: mechanical properties and influence of assumed constitutive relationships.

Poly(lactide)-block-poly(ethylene oxide)-block-poly(lactide) (PLA-PEO-PLA) triblock copolymers are known to form physical hydrogels in water as a result of the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and biodegradability have made them attractive for use as soft tissue scaffolds. However, the network junction points are not covalently cross-linked, and in a highly aqueous environment these hydrogels adsorb more water, transform from gel to sol, and lose the designed mechanical properties. In this article, a hydrogel was formed by the use of a novel two-step approach. In the first step, the end-functionalized PLA-PEO-PLA triblock was self-assembled into a physical hydrogel through hydrophobic micelle network junctions, and in the second step, this self-assembled physical network structure was locked into place by photo-cross-linking the terminal acrylate groups. In contrast with physical hydrogels, the photo-cross-linked gels remained intact in phosphate-buffered solution at body temperature. The swelling, degradation, and mechanical properties were characterized, and they demonstrated an extended degradation time (approximately 65 days), an exponential decrease in modulus with degradation time, and a tunable shear modulus (1.6-133 kPa). We also discuss the various constitutive relationships (Hookean, neo-Hookean, and Mooney-Rivlin) that can be used to describe the stress-strain behavior of these hydrogels. The chosen model and assumptions used for data fitting influenced the obtained modulus values by as much as a factor of 3.5, which demonstrates the importance of clearly stating one's data fitting parameters so that accurate comparisons can be made within the literature.

Micro- to nanoscale structure of biocompatible PLA-PEO-PLA hydrogels.

We observe large-scale structures in hydrogels of poly(l-lactide)-poly(ethylene oxide)-poly(l-lactide) (PLLA-PEO-PLLA) ranging in size from a few hundred nanometers to several micrometers. These structures are apparent through both ultra-small angle scattering (USAS) techniques and confocal microscopy. The hydrogels showed power law scattering in the USAS regime, which is indicative of scattering from fractal structures. The fractal dimension of the scattering from hydrogels revealed that the gels have large size aggregates with a mass fractal structure over the nanometer-to-micrometer length scales. The aggregates also seem to become more "dense" with an increase in the molecular weight of crystalline PLLA domains. Visualization through confocal microscopy confirms that the gels have a microstructure of interspersed micrometer-sized polymer inhomogeneities with water channels running between them. The presence of micrometer-sized water channels in the hydrogels has very important implications for biomedical applications.

Cavitation rheology for soft materials.

To guide the development of tissue scaffolds and the characterization of naturally heterogeneous biological tissues, we have developed a method to determine the local modulus at an arbitrary point within a soft material. The method involves growing a cavity at the tip of a syringe needle and monitoring the pressure of the cavity at the onset of a mechanical instability. This critical pressure is directly related to the local modulus of the material. The results focus on the network development of poly(lactide)-poly(ethylene oxide)-poly(lactide) triblock copolymer and poly(vinyl alcohol) hydrogels. These materials serve as model materials for tissue scaffolds and soft biological tissues. This new method not only provides an easy, efficient, and economical method to guide the design and characterization of soft materials, but it also provides quantitative data of the local mechanical properties in naturally heterogeneous materials.

Novel drug release profiles from micellar solutions of PLA-PEO-PLA triblock copolymers.

We have achieved nearly zero order sustained release behavior for periods up to 10-20 days for two hydrophobic drugs, sulindac and tetracaine, from 5wt.% micellar solutions of poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) triblock copolymer. The effect of PLA block length and crystallinity on the drug release profiles was studied. A series of polymers with constant PEO molecular weight of 8900Da and PLA molecular weight varying in the range of 4100-6500Da were examined. Drug release was found to be much faster for polymers with crystalline PLA blocks as compared to those with amorphous PLA blocks. The drug release rate also depends significantly on the length of the PLA block. Sustained release of sulindac was observed up to 20 days, and for tetracaine up to 10 days. By comparison, release of these drugs without polymeric carriers occurs over 4-6h. This result, along with a proposed mechanism for drug release, suggests that polymer-drug interactions significantly impact release profiles, causing slow and sustained release of the drug.

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.