Synthesis, characterization, and biomedical applications of novel photocrosslinkable hydrogels and biodendrimers.

摘要

Hydrogels based on natural polysaccharides hyaluronan and alginate were synthesized. Upon modification with methacrylate, these polymers were covalently photocrosslinked to form solid, clear, soft hydrogels (HA-MA and AA-MA). NMR spectroscopy confirmed modification and the degree of modification. The hydrogels exhibited second-order swelling with equilibrium swelling ratios of 11.1, 9.06, 7.90, and 14.3 for 3%, 8%, and 17% modified-HA-MA and 6% modified-AA-MA, respectively. These hydrogels displayed long-term stability and resistance to disintegration and enzymatic degradation. SEM and AFM revealed smooth and uniform surfaces. The 8% HA-MA hydrogel exhibited higher strength and resilience compared to the AA-MA hydrogel, as shown by stress vs. strain analysis and creep compliance and recovery. The HA-MA hydrogel behaved as a viscoelastic solid with near-complete creep recovery, whereas AA-MA behaved more liquid-like with low creep recovery and failure at 2 kP stress. The compressive moduli were 68, 130, 20, and 18 Pa and |G*| (stiffness) values were 850, 1800, 3400, and 330 Pa with low phase angles for 3%, 8%, and 17% HA-MA and 6% AA-MA, respectively. The HA-MA exhibited molecular weight dependent permeability; large molecules were unable to penetrate the hydrogel, whereas small molecules displayed facile diffusion. In vitro and in vivo experiments confirmed biocompatibility.; Rapid polymerization by an optical trigger allowed for controlled in situ photopolymerization in a minimally invasive manner indicating these hydrogels are relevant for biomedical applications such as sealing wounds and reconstructing tissues. 97% of experimental corneal perforations were completely sealed by in situ HA-MA application and photocrosslinking. The hydrogel also exhibited favorable diffusion characteristics for the treatment of diabetes by encapsulation of islets of Langerhans. Islets were successfully encapsulated and showed insulin response to glucose. Embedding chondrocytes within HA-MA for the repair of degenerated articular cartilage was also investigated. Chondrocytes embedded in HA-MA were 91% viable at 6 hours and 77% viable at 13 days.; The convergent synthesis of dendrons, dendrimers, and dendritic-linear hybrids composed of biocompatible monomers was conducted. G1 through G4 glycerol/succinate dendrons, a G3 dendrimer, and G3 dendron-PEG linear hybrid macromolecules were synthesized. These polymers were modified with methacrylate and photocrosslinked to form solid gels for biomedical applications.