Diffusion-Reaction Models of Genipin Incorporation into Fibrin Networks.

Genipin is a naturally derived small molecule that crosslinks compounds containing primary amines including many natural biopolymers. A diffusion-reaction model to predict the rates of delivery and incorporation of genipin into fibrin networks is presented. Genipin crosslink formation within fibrin hydrogels is a multi-step process that requires genipin diffusion and reaction with primary amines in hydrated networks. The reaction rate of genipin into fibrin gels was measured via spectroscopy while the rate of marginal crosslink formation was measured by rheology. Covalent coupling between genipin and primary amines in fibrin gels obeys second-order kinetics in genipin concentration with an effective activation energy of -71.9 ± 3.2 kJ-mol-1. Genipin diffusion-reaction within fibrin gels exhibits Thiele moduli between 0.02-0.28, which suggests that the systems studied herein are reaction-limited. Genipin-crosslinked fibrin clots are resistant to fibrinolytic degradation as measured by rheology. Finally, active genipin can be delivered from poly(D,L-lactide-co-glycolide) matrices to gels at rates that are comparable to the characteristic rate of incorporation in fibrin networks. Taken together, this work establishes a quantitative framework to engineer controlled release systems for genipin delivery into protein-based hydrogel networks.

Photoreconfigurable polymers for biomedical applications: chemistry and macromolecular engineering.

Stimuli-responsive polymers play an important role in many biomedical technologies. Light responsive polymers are particularly desirable because the parameters of irradiated light and diverse photoactive chemistries produce a large number of combinations between functional materials and associated stimuli. This Review summarizes recent advances in utilizing photoactive chemistries in macromolecules for prospective use in biomedical applications. Special focus is granted to selection criterion when choosing photofunctional groups. Synthetic strategies to incorporate these functionalities into polymers and networks with different topologies are also highlighted herein. Prospective applications of these materials are discussed including programmable matrices for controlled release, dynamic scaffolds for tissue engineering, and functional coatings for medical devices. The article concludes by summarizing the state of the art in photoresponsive polymers for biomedical applications including current challenges and future opportunities.

Photoresponsive hydrogel networks using melanin nanoparticle photothermal sensitizers.

Photoreconfigurable and photodegradable polymeric networks have broad utility as functional biomaterials for many applications in medicine and biotechnology. The vast majority of these functional polymers are synthesized using chemical moieties that may be cytotoxic in vivo. Materials synthesized from these substituents also pose unknown risk upon implantation and thus will encounter significant regulatory challenges prior to use in vivo. This work describes a strategy to prepare photodegradable hydrogel networks that are composed of well-characterized synthetic polymers and natural melanin pigments found within the human body. Self-assembled networks of poly(l-lactide-co-glycolide)-poly(ethylene glycol) ABA triblock copolymers are doped with melanin nanoparticles to produce reconfigurable networks based on photothermal phase transitions. Self-assembled hydrogel networks with melanin nanoparticles exhibit a storage modulus ranging from 1.5 ± 0.6 kPa to 8.0 ± 7.5 kPa as measured by rheology. The rate of UV-induced photothermal heating was non-monotonic and varied as a function of melanin nanoparticle loading. A maximum steady state temperature increase of 20.5 ± 0.30 °C was measured. Experimental heating rates were in close agreement with predictions based on attenuation of light in melanins via photothermal absorption and Mie scattering. The implications of melanin nanoparticles on hydrogel network formation and light-induced disintegration were also characterized by rheology and dynamic light scattering. Taken together, this class of photoreconfigurable hydrogels represents a potential strategy for photodegradable polymers with increased likelihood for clinical translation.

Reconfigurable biodegradable shape-memory elastomers via Diels-Alder coupling.

Synthetic biodegradable elastomers are a class of polymers that have demonstrated far-reaching utility as biomaterials for use in many medical applications. Biodegradable elastomers can be broadly classified into networks prepared by either step-growth or chain-growth polymerization. Each processing strategy affords distinct advantages in terms of capabilities and resulting properties of the network. This work describes the synthesis, processing, and characterization of cross-linked polyester networks based on Diels-Alder coupling reactions. Hyperbranched furan-modified polyester precursors based on poly(glycerol-co-sebacate) are coupled with bifunctional maleimide cross-linking agents. The chemical and thermomechanical properties of the elastomers are characterized at various stages of network formation. Experimental observations of gel formation are compared to theoretical predictions derived from Flory-Stockmayer relationships. This cross-linking strategy confers unique advantages in processing and properties including the ability to fabricate biodegradable reconfigurable covalent networks without additional catalysts or reaction byproducts. Reconfigurable biodegradable networks using Diels-Alder cycloaddition reactions permit the fabrication of shape-memory polymers with complex permanent geometries. Biodegradable elastomers based on polyester networks with molecular reconfigurability achieve vastly expanded properties and processing capabilities for potential applications in medicine and beyond.