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An in situ gel-forming system composed of rutin- and tyramine-conjugated chitosan derivatives, horseradish peroxidase (HRP), and hydrogen peroxide (H(2)O(2)) was prepared and applied to dermal wound repair. Rutin was employed to enhance production and accumulation of extracellular matrix in the healing process. In vitro study demonstrates that released rutin significantly enhanced cell proliferation as compared with media without rutin. In vivo wound healing study was performed by injecting hydrogels on rat dorsal wounds with a diameter of 8 mm for 14 days. Histological results demonstrated that rutin-conjugated hydrogel exhibited enhancement of wound healing as compared with treatments with PBS, hydrogel without rutin, and a commercialized wound dressing (Duoderm). More specifically, rutin-conjugated hydrogels induced better defined formation of neo-epithelium and thicker granulation, which is closer to the original epithelial tissue. As a result, this study suggests that the in situ gel-forming system can be a promising injectable gel-type wound dressing.

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Kidney diseases are a worldwide public health issue. Renal tissue regeneration using functional scaffolds with biomaterials has attracted a great deal of attention due to limited donor organ availability. Here, we developed a bioinspired scaffold that can efficiently induce renal tissue regeneration. The bioinspired scaffold was designed with poly(lactide- co -glycolide) (PLGA), magnesium hydroxide (Mg(OH) 2 ), and decellularized renal extracellular matrix (ECM). The Mg(OH) 2 inhibited materials-induced inflammatory reactions by neutralizing the acidic microenvironment formed by degradation products of PLGA, and the acellular ECM helped restore the biological function of kidney tissues. When the PLGA/ECM/Mg(OH) 2 scaffold was implanted in a partially nephrectomized mouse model, it led to the regeneration of renal glomerular tissue with a low inflammatory response. Finally, the PLGA/ECM/Mg(OH) 2 scaffold was able to restore renal function more effectively than the control groups. These results suggest that the bioinspired scaffold can be used as an advanced scaffold platform for renal disease treatment.

Chronic kidney disease is now recognized as a major health problem, but current therapies including dialysis and renal replacement have many limitations. Consequently, biodegradable scaffolds to help repairing injured tissue are emerging as a promising approach in the field of kidney tissue engineering. Poly(lactic-co-glycolic acid) (PLGA) is a useful biomedical material, but its insufficient biocompatibility caused a reduction in cell behavior and function. In this work, we developed the kidney-derived extracellular matrix (ECM) incorporated PLGA scaffolds as a cell supporting material for kidney tissue regeneration. Biomimetic PLGA scaffolds (PLGA/ECM) with different ECM concentrations were prepared by an ice particle leaching method, and their physicochemical and mechanical properties were characterized through various analyses. The proliferation of renal cortical epithelial cells on the PLGA/ECM scaffolds increased with an increase in ECM concentrations (0.2, 1, 5, and 10%) in scaffolds. The PLGA scaffold containing 10% of ECM has been shown to be an effective matrix for the repair and reconstitution of glomerulus and blood vessels in partially nephrectomized mice in vivo, compared with only PLGA control. These results suggest that not only can the tissue-engineering techniques be an effective alternative method for treatment of kidney diseases, but also the ECM incorporated PLGA scaffolds could be promising materials for biomedical applications including tissue engineered scaffolds and biodegradable implants.

Fast in situ forming supramolecular hydrogels consisted of the tyramine-conjugated supramolecular structures and chitosan derivative were prepared via an enzymatic reaction with horseradish peroxidase (HRP) and hydrogen peroxide (H(2)O(2)). The gel formation was varied within a time period of 5 s to 10 min by controlling the concentrations of HRP, H(2)O(2), and polymers. Tyramine conjugation at different sites of the supramolecular structure resulted in significant changes in physical properties and the degradation time of the hydrogels that were confirmed by water uptake, compressive strength and degradation tests. In addition, the hydrogels showed a good cytocompatibility in vitro. These hydrogels could be promising injectable biomaterials with adjustable degradation times to control both the cellular behaviors as a regenerative cell matrix and the drug release behavior as a drug delivery vehicle.

Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts resulting from degradation can generate vigorous inflammatory reactions, often leading to clinical failure. We present an approach to prevent acid-induced inflammatory responses associated with biodegradable polymers, here poly(lactide- co-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)) nanoparticles, which neutralize the acidic environment. In particular, we demonstrated that incorporating the modified Mg(OH) nanoparticles within degradable coatings on drug-eluting arterial stents efficiently attenuates the inflammatory response and in-stent intimal thickening by more than 97 and 60%, respectively, in the porcine coronary artery, compared with that of drug-eluting stent control. We also observed that decreased inflammation allows better reconstruction of mouse renal glomeruli in a kidney tissue regeneration model. Such modified Mg(OH) nanoparticles may be useful to extend the applicability and improve clinical success of biodegradable devices used in various biomedical fields.