Introduction

Agarose, a marine-derived polysaccharide, is a widely used biomedicine due to its biocompatibility, gel-forming capacity, and inert nature^[1]. However, its poor biodegradability and mechanical limitations restrict further clinical use^[2]. To address this, we propose the synthesis of a novel biodegradable semi-IPN combining agarose with methacrylate-based polymers (DMAEMA, HEMA, OEGMA). The degradation of these networks will be enhanced by incorporating monomers like FMA and VMA, which can establish labile cross-linking points, thereby preventing the formation of microplastics.

Methods

Copolymers were synthesized via living polymerizations —RAFT and ATRP— with reaction parameters systematically optimized. Following dialysis purification, cross-linking of copolymers was performed using Diels–Alder chemistry, thiol–ene reactions, or ionic interactions, either individually or within an agarose matrix. The resulting materials were characterized by NMR, SEC, SEM, and rheological analyses.

Results and Discussion

Both polymerization techniques successfully yielded copolymers with the targeted monomer ratios, although RAFT provided narrower dispersity. Among the monomers tested, HEMA produced the strongest hydrogels under identical cross-linking conditions, while thiol–ene cross-linking became the most effective strategy, offering superior rheological properties—even outperforming dual-cross-linked systems (Diels–Alder + ionic). Diels–Alder cross-linked networks did not exhibit retro-Diels–Alder behavior upon heating unless equilibrium was deliberately shifted. Incorporation of agarose to form semi-IPN enhanced the rheological performance of all systems compared to blanks, with the OEGMA-based, Diels–Alder cross-linked network performing best. SEM analysis revealed well-defined microporous architectures, supporting the potential of these semi-IPNs for biomedical applications.

Conclusions

Novel agarose-based biomaterials with enhanced mechanical strength and porous microstructures were developed for biomedical applications. RAFT and ATRP effectively yielded copolymers from HEMA, OEGMA, DMAEMA, FMA, and VMA with targeted monomer ratios. Gelation was achieved via covalent and ionic cross-linking, with Diels–Alder yielding the most robust semi-IPN.

References

[1] Molecules. 2023, doi: 10.3390/molecules21111577

[2] Pharmaceutics. 2023, doi: 10.3390/pharmaceutics15102514