Hydrogels have been applied to improve stem cell therapy and drug delivery, but current hydrogel-based delivery methods are inefficient in clinical settings due to difficulty in handling and treatment processes, and low off-the-shelf availability. To overcome these limitations, an adhesive hyaluronic acid (HA) hydrogel patch is developed that acts as a ready-to-use tissue tape for therapeutic application. The HA hydrogel patches functionalized with phenolic moieties (e.g., catechol, pyrogallol) exhibit stronger tissue adhesiveness, greater elastic modulus, and increased off-the-shelf availability, compared with their bulk solution gel form. With this strategy, stem cells are efficiently engrafted onto beating ischemic hearts without injection, resulting in enhanced angiogenesis in ischemic regions and improving cardiac functions. HA hydrogel patches facilitate the in vivo engraftment of stem cell-derived organoids. The off-the-shelf availability of the hydrogel patch is also demonstrated as a drug-loaded ready-made tissue tape for topical drug delivery to promote wound healing. Importantly, the applicability of the cross-linker-free HA patch is validated for therapeutic cell and drug delivery. The study suggests that bioinspired phenolic adhesive hydrogel patches can provide an innovative method for simple but highly effective cell and drug delivery, increasing the off-the-shelf availability-a critically important component for translation to clinical settings.

Induced hepatic (iHep) cells generated by direct reprogramming have been proposed as cell sources for drug screening and regenerative medicine. However, the practical use of a 3D hepatic tissue culture comprised of iHep cells for drug screening and toxicology testing has not been demonstrated. In this study, a 3D vascularized liver organoid composed of iHep cells and a decellularized liver extracellular matrix (LEM) cultured in a microfluidic system is demonstrated. iHep cells are generated by transfection with polymer nanoparticles and plasmids expressing hepatic transcription factors. The iHep cells are cocultured with endothelial cells in the 3D LEM hydrogel in a microfluidic-based cell culture device with a continuous dynamic flow of media. The resultant 3D vascularized liver organoids maintained under this physiologically relevant culture microenvironment exhibit improved hepatic functionalities, metabolic activity, biosynthetic activity, and drug responses. Finally, the feasibility of using the iHep-based 3D liver organoid as a highthroughput drug screening platform, as well as its use in a multiorgan model comprised of multiple internal organoids is confirmed. The study suggests that a combined strategy of direct reprogramming, matrix engineering, and microfluidics can be used to develop a highly functional, standardized, drug screening, and toxicological analysis platform.

Triboelectric nanogenerators (TENGs) can be an effective cell reprogramming platform for producing functional neuronal cells for therapeutic applications. Triboelectric stimulation accelerates nonviral direct conversion of functional induced neuronal cells from fibroblasts, increases the conversion efficiency, and induces highly matured neuronal phenotypes with improved electrophysiological functionalities. TENG devices may also be used for biomedical in vivo reprogramming.

No abstract

Matrigel, a mouse tumor extracellular matrix protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to-batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal tissue-derived extracellular matrix hydrogels are suitable substitutes for Matrigel in gastrointestinal organoid culture. We found that the development and function of gastric or intestinal organoids grown in tissue extracellular matrix hydrogels are comparable or often superior to those in Matrigel. In addition, gastrointestinal extracellular matrix hydrogels enabled long-term subculture and transplantation of organoids by providing gastrointestinal tissue-mimetic microenvironments. Tissue-specific and age-related extracellular matrix profiles that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that extracellular matrix hydrogels derived from decellularized gastrointestinal tissues are effective alternatives to the current gold standard, Matrigel, and produce organoids suitable for gastrointestinal disease modeling, drug development, and tissue regeneration.