Postoperative adhesions occur widely in various tissues, bringing the risk of secondary surgery and increased medical burden. Hydrogel barriers with Janus-adhesive ability can achieve physical isolation of adjacent tissues and are therefore considered an ideal solution. However, integrating endoscopic delivery convenience and viscoelastic Janus hydrogel formation remains a great challenge. Here, we present a report of the in situ formation of Janus-adhesive hydrogel barrier using a sprayable fast-Janus-gelation (FJG) powder. We first methacrylate the polysaccharide macromolecules to break the intermolecular hydrogen bonds and impart the ability of rapid hydration. FJG powder can rapidly absorb interfacial water and crosslink through borate ester bonds, forming a toughly adhesive viscoelastic hydrogel. The Janus barrier can be simply formed by further hydrating the upper powder with cationic solution. We construct rat models to demonstrate the antiadhesions efficiency of viscoelastic FJG hydrogels in organs with different motion modalities (e.g., intestine, heart, liver). We also developed a low-cost delivery device with a standardized surgical procedure and further validated the feasibility and effectiveness of FJG powder in minimally invasive surgery using a preclinical translational porcine model. Considering the advantages in terms of therapeutic efficacy, clinical convenience, and commercialization, our results reveal the great potential of Janus-gelation powder materials as a next-generation antiadhesions barrier.
Periodontitis can cause irreversible defects in the periodontal ligament (PDL), the regeneration of which is the major obstacle to the clinical treatment of periodontitis. Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration. However, existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium, which may have been shown as an important role in tissue regeneration. Meanwhile, the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive. In this study, we developed a bi-crosslinking viscoelastic hydrogel (Alg-PBA/Spd) by integrating phenylboronic acid-modified alginate with anti-inflammatory agent (spermidine) through borate ester and B–N coordination bonds, where spermidine will be released with the degradation of the hydrogel. Alg-PBA/Spd hydrogel is biocompatible, injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking. We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage. Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.
After myocardial infarction (MI), ventricular dilation and the microscopic passive stretching of the infarcted border zone is the meaning contributor to the continuous expansion of myocardial fibrosis. Epicardial hydrogel patches have been demonstrated to alleviate this sequela of MI in small-animal models. However, these have not been successfully translated to humans or even large animals, in part because of challenges in attaining both the greater stiffness and slower viscoelastic relaxation that mathematical models predict to be optimal for application to larger, slower-beating hearts. Here, using borate-based dynamic covalent chemistry, we develop an injectable “heart rate matched” viscoelastic gelatin (VGtn) hydrogel with a gel point tunable across the stiffnesses and frequencies that are predicted to transspecies and cross-scale cardiac repair after MI. Small-animal experiments demonstrated that, compared to heart rate mismatched patches, the heart rate matched VGtn patches inhibited ventricular bulging and attenuated stress concentrations in the myocardium after MI. In particular, the viscoelastic patch can coordinate the microscopic strain at the infarction boundary. VGtn loaded with anti-fibrotic agents further reduced myocardial damage and promoted angiogenesis in the myocardium. The tuned heart rate matched patches demonstrated similar benefits in a larger-scale and lower heart rate porcine MI model. Results suggest that heart rate matched VGtn patches may hold potential for clinical translation.