Marine mussels secrete adhesive proteins to attach to solid surfaces. These proteins contain phenolic and basic amino acids exhibiting wet adhesion properties. This study used a mussel-inspired hemostatic polymer, chitosan-catechol, to treat gastrointestinal bleeding caused by endoscopic mucosal resection in a heparinized porcine model. We aimed to evaluate the hemostatic efficacy and short-term safety of this wet adhesive chitosan-catechol. We used 15 heparinized pigs. Four iatrogenic bleeding ulcers classified as Forrest Ib were created in each pig using an endoscopic mucosal resection method. One ulcer in each pig was untreated as a negative control (no-treatment group). The other three ulcers were treated with gauze (gauze group), argon plasma coagulation (APC group), and chitosan-catechol hemostatic agent (CHI-C group) each. The pigs were sacrificed on Days 1, 5, and 10, and histological examination was performed (n = 5 per day). Rapid hemostasis observed at 2 min after bleeding was 93.3% (14/15) in the CHI-C group, 6.7% (1/15) in the no-treatment group, 13.3% (2/15) in the gauze group, and 86.7% (13/15) in the APC group. No re-bleeding was observed in the CHI-C group during the entire study period. However, a few re-bleeding cases were observed on Day 1 in the no-treatment, gauze, and APC groups and on Day 5 in the gauze and APC groups. On histological analysis, the CHI-C group showed the best tissue healing among the four test groups. Considering the results, chitosan-catechol is an effective hemostatic material with reduced re-bleeding and improved healing.
Background/Objectives: Topical hemostatic biomaterials are used to control diffuse parenchymal bleeding during hepatectomy. TachoSil is a widely used standard fibrin sealant patch. We evaluated the efficacy and safety of InnoSEAL Plus DL, a novel bioinspired absorbable chitosan–catechol/gelatin hemostatic patch, compared with TachoSil. Methods: This multicenter, randomized, single-blind, active-controlled, parallel-group noninferiority trial enrolled adults undergoing hepatectomy who had persistent oozing from the hepatic transection surface despite primary hemostasis. Participants were randomized in a 1:1 ratio to receive InnoSEAL Plus DL or TachoSil. The primary endpoint was hemostatic success within 3 min of application, with a prespecified noninferiority margin of −19.4 percentage points (pp). Safety was assessed up to 30 days postoperatively. Results: Ninety patients were randomized (45 per group). In the per-protocol population, 3 min hemostatic success was achieved in 100.0% of both the InnoSEAL Plus DL (43/43) and TachoSil (41/41) groups. The risk difference was 0.0 pp, and the lower bound of the one-sided 97.5% confidence interval was −8.2 pp, confirming noninferiority. The mean time to hemostasis was similar between groups (1.2 vs. 1.3 min), and no intraoperative rebleeding occurred. Adverse events were reported in 78/90 patients (86.7%) and serious adverse events in 6/90 (6.7%); the latter were typical post-hepatectomy events unrelated to the study devices. No deaths were reported. Conclusions: InnoSEAL Plus DL was noninferior to TachoSil for achieving rapid intraoperative hemostasis during hepatectomy, with no unexpected safety concerns. This bioinspired hemostatic patch is an effective alternative to fibrin sealant, without the use of human-derived proteins.
Injectable hydrogels hold promise for localized drug delivery and regenerative medicine, yet their clinical translation remains limited by reliance on backbone modification or exogenous physicochemical triggers that complicate delivery. Here, we exploit an unavoidable aspect of clinical administration, shear, which is generated during injection through catheters and needles. We introduce SIGMA (Shear-Induced Gelation by Microbead Aggregation), a system composed of gelatin microbeads that remain flowable during injection but rapidly assemble into cohesive hydrogel under confined shear, without exogenous physicochemical triggers such as temperature, pH, light, or chemical crosslinkers. Gelation was tunable by varying flow path length, mixing cycles, particle sizes, or introducing air–liquid interfaces, enabling transitions from a weak dispersion (∼11.3 Pa) to robust gels with storage moduli up to ∼5 kPa and compressive strengths approaching ∼800 kPa. Circular dichroism and gel permeation chromatography revealed shear-induced intermolecular associations without evidence of chain scissions. The platform further enabled post-encapsulation drug loading with tunable release governed by shear-programmed network density. In vitro and in vivo studies confirmed cytocompatibility, biodegradability, systemic safety, and superior submucosal lift compared with saline. Together, SIGMA establishes a mechanically actuated, clinically adaptable hydrogel platform for minimally invasive surgery and localized drug delivery.
Conventional gelatin's gel‐to‐sol transition upon heating restricts its utility in biomedical applications that benefit from a gel state at physiological temperatures such as Pluronic F127 and poly(NIPAAm). Herein, we present “rev‐Gelatin”, a gelatin engineered with reverse thermo‐responsive properties that undergoes a sol‐to‐gel transition as temperature rises from ambient to body temperature. Inspired by the phase dynamics of common materials like candy and ice cubes, whose surfaces soften or partially melt under warming, facilitating inter‐object adhesion‐ rev‐Gelatin leverages this concept to achieve fluidity at room temperature for easy injectability. At ambient temperature, rev‐Gelatin exists as a microgel solution with sufficient fluidity in the sol state. However, upon exposure to elevated temperatures approaching physiological temperature, rev‐Gelatin microgels coalesce through surface melting, forming a stable gel. This sol‐to‐gel transition is especially advantageous for hemostatic applications. Upon contact with blood, the temperature elevation induces rapid gelation of rev‐Gelatin, effectively creating a barrier that reduces bleeding time and blood loss. Additionally, rev‐Gelatin shows promise as a submucosal injection agent for gastrointestinal surgeries, making it a new class of thermo‐sensitive biomaterials.