Recently, a great deal of research has focused on the study of self-healing hydrogels possessing electronic conductivity due to their wide applicability for use in biosensors, bioelectronics, and energy storage. The low solubility, poor biocompatibility, and lack of effective stimuli-responsive properties of their sp 2 carbon-rich hybrid organic polymers, however, have proven challenging for their use in electroconductive self-healing hydrogel fabrication. In this study, we developed stimuli-responsive electrochemical wireless hydrogel biosensors using ureidopyriminone-conjugated gelatin (Gel-UPy) hydrogels that incorporate diselenide-containing carbon dots (dsCD) for cancer detection. The cleavage of diselenide groups of the dsCD within the hydrogels by glutathione (GSH) or reactive oxygen species (ROS) initiates the formation of hydrogen bonds that affect the self-healing ability, conductivity, and adhesiveness of the Gel-UPy/ dsCD hydrogels. The Gel-UPy/dsCD hydrogels demonstrate more rapid healing under tumor conditions (MDA-MB-231) compared to that observed under physiological conditions (MDCK). Additionally, the cleavage of diselenide bonds affects the electrochemical signals due to the degradation of dsCD. The hydrogels also exhibit excellent adhesiveness and in vivo cancer detection ability after exposure to a high concentration of GSH or ROS, and this is comparable to results observed in a low concentration environment. Based on the combined self-healing, conductivity, and adhesiveness properties of the Gel-UPy/ dsCD, this hydrogel exhibits promise for use in biomedical applications, particularly those that involve cancer detection, due to its selectivity and sensitivity under tumor conditions.

Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.

The development of bioadhesives has become an emerging research field for tissue sealants, wound dressings, and hemostatic agents. However, assembling hydrogels using bioadhesive‐mediated attachment remains a challenging task. Significantly high water content (>90%) in hydrogels compared to that of biological tissues is the main cause of failure. Considering that hydrogels are primary testing scaffolds mimicking in vivo environments, developing strategies to assemble hydrogels that exhibit diverse properties is important. Self‐healing gels have been reported, but such gels often lack biocompatibility, and two gel pieces should be identical in chemistry for assembly, thus not allowing co‐existence of diverse biological environments. Herein, a mussel‐mimetic cis‐diol‐based adhesive, alginate‐boronic acid, that exhibits pH‐responsive curing from a viscoelastic solution to soft gels is developed. Associated mechanisms are that 1) polymeric diffusion occurs at interfaces utilizing intrinsic high water content; 2) the conjugated cis‐diols strongly interact/entangle with hydrogel chains; 3) curing processes begin by a slight increase in pH, resulting in robust attachment of diverse types of hydrogel building blocks for assembly. The findings obtained with alginate‐boronic acid glues suggest a rational design principle to attach diverse hydrogel building blocks to provide platforms mimicking in vivo environments.

No abstract

Background: Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensing platforms. The unique aspect of PBA-polymers is their interactions with diols, which result in reversible, covalent bond formation. This very nature of reversible bonding between boronic acids and diols has been fundamental to their applications in the biomedical area. Methods: We have searched peer-reviewed articles including reviews from Scopus, PubMed, and Google Scholar with a focus on the 1) chemistry of PBA, 2) synthesis of PBA-polymers, and 3) their biomedical applications. Results: We have summarized approximately 179 papers in this review. Most of the applications described in this review are focused on the unique ability of PBA molecules to interact with diol molecules and the dynamic nature of the resulting boronate esters. The strong sensitivity of boronate ester groups towards the surrounding pH also makes these molecules stimuli-responsive. In addition, we also discuss how the re-arrangement of the dynamic boronate ester bonds renders PBA-based materials with other unique features such as self-healing and shear thinning. Conclusion: The presence of PBA in the polymer chain can render it with diverse functions/ relativities without changing their intrinsic properties. In this review, we discuss the development of PBA polymers with diverse functions and their biomedical applications with a specific focus on the dynamic nature of boronate ester groups.

The intraperitoneal (IP) cavity is the largest fluid-filled space in the body and contains important organs. Although peritoneal fluid from the abdominal cavity lubricates and allows organ motion, this fluid also effectively prevents polymeric material implantation. Anastomotic leakage after surgery has been reported but few sealing methods have been developed. Herein, a fluidresistant adhesive called IP patch is reported that seals intestinal neo-anastomosis sites, preventing anastomotic leakage after colorectal surgery. The bursting pressure, which is the most important index of the degree of healing after colorectal anastomosis surgery, is measured from an IP patch applied to rats (188.3 ± 14.5 mmHg) and is highly similar to the pressure observed from normal tissue (210.2 ± 22.9 mmHg). Additionally, IP patches can act as unprecedented local drug reservoirs due to the aforementioned tissue adhesive property. Drug-loaded IP patches successfully treated multiple-site occurrence of small peritoneal cancerous colonies. The anticancer drug-loaded IP patches are applied to potential risk regions for recurrent and metastasized cancer in the IP cavity after the resection of peritoneal solid tumors. Thus, the multifunctionality of IP patches can be usefully exploited as an adhesive biomaterial that works effectively in difficult-to-treat diseases observed in IP environments.

Here, in Ppara−/− mice, we found that an increased DNL stimulated the cartilage degradation and identified ACOT12 as a key regulatory factor. Suppressed level of ACOT12 was observed in cartilages of OA patient and OA-induced animal. To determine the role and association of ACOT12 in the OA pathogenesis, we generated Acot12 knockout (KO) (Acot12−/−) mice using RNA-guided endonuclease. Acot12−/− mice displayed the severe cartilage degradation with the stimulation of matrix MMPs and chondrocyte apoptosis through the accumulation of acetyl CoA. Delivery of acetyl CoA-conjugated chitosan complex into cartilage stimulated DNL and cartilage degradation. Moreover, restoration of ACOT12 into human OA chondrocytes and OA-induced mouse cartilage effectively rescued the pathophysiological features of OA by regulating DNL. Taken together, our study suggested ACOT12 as a novel regulatory factor in maintaining cartilage homeostasis and targeting ACOT12 could contribute to developing a new therapeutic strategy for OA.

Recently, there has been growing interest in replacing severely damaged salivary glands with artificial salivary gland functional units created in vitro by tissue engineering approaches. Although various materials such as poly­(lactic-co-glycolic acid), polylactic acid, poly­(glycolic acid), and polyethylene glycol hydrogels have been used as scaffolds for salivary gland tissue engineering, none of them is effective enough to closely recapitulate the branched structural complexity and heterogeneous cell population of native salivary glands. Instead of discovering new biomaterial candidates, we synthesized hyaluronic acid–catechol (HACA) conjugates to establish a versatile hyaluronic acid coating platform named “NiCHE (nature-inspired catechol-conjugated hyaluronic acid environment)” for boosting the salivary gland tissue engineering efficacy of the previously reported biomaterials. By mimicking hyaluronic acid-rich niche in the mesenchyme of embryonic submandibular glands (eSMGs) with NiCHE coating on substrates including polycarbonate membrane, stiff agarose hydrogel, and polycaprolactone scaffold, we observed significantly enhanced cell adhesion, vascular endothelial and progenitor cell proliferation, and branching of in vitro-cultured eSMGs. High mechanical stiffness of the substrate is known to inhibit eSMG growth, but the NiCHE coating significantly reduced such stiffness-induced negative effects, leading to successful differentiation of progenitor cells to functional acinar and myoepithelial cells. These enhancement effects of the NiCHE coating were due to the increased proliferation of vascular endothelial cells via interaction between CD44 and surface-immobilized HAs. As such, our NiCHE coating platform renders any kind of material highly effective for salivary gland tissue culture by mimicking in vivo embryonic mesenchymal HA. Based on our results, we expect the NiCHE coating to expand the range of biomaterial candidates for salivary glands and other branching epithelial organs.