Degradable hydrogel adhesives with multifunctional advantages are promising to be candidates as hemostatic agents, surgical sutures, and wound dressings. In this study, hydrogel adhesives are constructed by catechol-conjugated gelatin from natural resource, iron ions (Fe 3+ ), and a synthetic polymer. Specifically, the latter is prepared by the radical ring-opening copolymerization of a cyclic ketene acetal monomer 5,6-benzo-2-methylene-1,3-dioxepane and N-(2-ethyl p-toluenesulfonate) maleimide. By the incorporation of ester bonds in the backbone and the combination with quaternary ammonium salt pendants in the polymer, it exhibits excellent degradability and antibacterial property. Remarkably, doping the synthetic polymer into the 3,4-dihydroxyphenylacetic acid-modified gelatin network forms a semi-interpenetrating polymer network which can effectively improve the rigidity, tissue adhesion, and antibacterial property of fabricated hydrogel adhesives. Moreover, non-covalent bonds from coordination interaction between catechol and Fe 3+ contribute to the fast self-healing of the developed hydrogel adhesives. These hydrogel adhesives with the multiple merits including the degradability, enhanced tissue adhesion, superior self-healing, good cytocompatibility, and antibacterial property show the great potential to be used as tissue adhesives in biomedical fields.

Sequence-defined polymers prepared from vinyl monomers attract tremendous research interests in mimicking the precise primary sequence and remarkable biological functions of natural biopolymers. Sequential single unit monomer insertion (SUMI) via the reversible addition–fragmentation chain-transfer (RAFT) mechanism shows the ability to assemble vinyl monomers in defined orders efficiently with high yields. However, the approach of RAFT SUMI to produce both degradable and biocompatible sequence-defined oligomers has not been reported yet. In this research, we report the radical ring-opening SUMI of a cyclic ketene acetal monomer, 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), with the alternating insertion of N-substituted maleimides to afford sequence-defined oligomers. The oligomers can be degraded into shorter fragments due to the ester bonds incorporated in the backbone. Moreover, one prepared trimer demonstrates the biocompatibility to the investigated human normal cells while showing the cytotoxic effect against the studied human cancer cells. The properties of the produced oligomers endowed by BMDO hold promise for decoding information stored in sequence-defined polymers and the potential in biomedical applications.

Sequence‐defined and degradable polymers can mimic biopolymers, such as peptides and DNA, to undertake life‐supporting functions in a chemical way. The design and development of well‐structured oligomers/polymers is the most concern for the public, even to further uncover their degradation process illustrating the degraded products and their properties. However, seldom investigation has been reported on the aforementioned aspects. In this work, the alternating photo‐reversible addition‐fragmentation chain‐transfer (photo‐RAFT) single unit monomer insertion (SUMI) of different N‐substituted maleimides and thermal radical ring‐opening SUMI of a cyclic ketene acetal monomer (i.e., 5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO)) is adopted, to produce two degradable pentamers owing to the conversion of the exo‐methylene group of BMDO into ester bonds along the main chains of the prepared products. Moreover, the possible degraded approach of pentamers is studied by combining high‐resolution mass spectrometry (HRMS) and liquid chromatography‐mass spectrometry (LC‐MS) for the first time. This work also sheds light on the precise structures and cytotoxicity of SUMI products and their degraded compounds, proposing a detailed and credible outlook for biomedical applications.