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.
The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF). Sprague-Dawley female rats (8 weeks old, 182.2 +/- 7.2 g) underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 x 10(6) cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-h urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients. No significant differences in blood urea nitrogen and creatinine concentration were observed between the MSC group and the untreated CRF group. However, the weight gain in the MSC group was greater than those in the CRF group after 4 months. Proteinuria in the MSC group was less than that in the CRF group over time. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between these two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis. These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.
Chondroitin sulfate (CS), the main component of cartilage extracellular matrix, has attracted attention as a biomaterial for cartilage tissue engineering. However, current CS hydrogel systems still have limitations for application in successful cartilage tissue engineering owing to their unsuitable degradation kinetics, insufficient mechanical similarity, and lack of integration with the native cartilage tissue. In this study, using mussel adhesive-inspired catechol chemistry, we developed a functional CS hydrogel that exhibits tunable physical and mechanical properties as well as excellent tissue adhesion for efficient integration with native tissues. Various properties of the developed catechol-functionalized CS (CS-CA) hydrogel, including swelling, degradation, mechanical properties, and adhesiveness, could be tailored by varying the conjugation ratio of the catechol group to the CS backbone and the concentration of the CS-CA conjugates. CS-CA hydrogels exhibited significantly increased modulus (∼10 kPa) and superior adhesive properties (∼3 N) over conventional CS hydrogels (∼hundreds Pa and ∼0.05 N). In addition, CS-CA hydrogels incorporating decellularized cartilage tissue dice promoted the chondrogenic differentiation of human adipose-derived mesenchymal stem cells by providing a cartilage-like microenvironment. Finally, the transplantation of autologous cartilage dice using tissue-adhesive CS-CA hydrogels enhanced cartilage integration with host tissue and neo-cartilage formation owing to favorable physical, mechanical, and biological properties for cartilage formation. In conclusion, our study demonstrated the potential utility of the CS-CA hydrogel system in cartilage tissue reconstruction.
This paper focuses on optimal operation schedule of a Microgrid that is interconnected to the power grid. We develop a mathematical model to compute the optimal operation schedule that embodies demand response. Integer Programming optimization is used to this end. Our model incorporates the electricity load into three types: fixed, transferable, and useraction loads. The transferable load plays a key role in molding demand response. Experimental results show that the proposed model exploits the demand elasticity and significantly reduces the total operation cost. Also observed from the experiments are the impact of the uncertainty in renewable distributed generators on operation schedule and total cost and the role of power storages for enhancing the demand elasticity with respect to user-action loads and for reserving power against high price.
Injectable fillers mainly aim to augment tissue volume and correct wrinkles in cosmetic and plastic reconstructions. However, the development of long-lasting, injectable fillers with minimal complications of pain, toxicity, and displacement has been challenging because of the absence of reliable cross-linking chemistry. Here, we report a novel cross-linker-free injectable hydrogel formulated by autoxidation as a highly biocompatible, easily injectable, and long-term volumetrically stable filler agent. Self-cross-linkable hyaluronic acid (SC-HA) with gallol moieties could form a hydrogel via autoxidation of gallols in vivo without additional cross-linking agents. The gelation of SC-HA in situ after injection is accelerated by the self-production of oxygen species and endogenous peroxidase in vivo. The SC-HA filler does not require a high injection force, thus minimizing pain, bleeding, and tissue damage-associated complications. In addition, improved tissue adhesiveness of the SC-HA hydrogel by oxidized gallols (shear strength; 2 kPa) prevented displacement of the filler constructs from the injection site. The SC-HA filler retained its mechanical properties in vivo (600–700 Pa) for wrinkle correction and volumetric augmentation up to 1 year after injection. Overall, the performance of the SC-HA hydrogel as an injectable dermal filler was superior to that of commercially available, chemically cross-linked biphasic HA filler composites in terms of injectability, tissue adhesiveness, and long-term volumetric augmentation. Our injectable HA hydrogel with no need of cross-linkers provides a long-lasting filler that has clinical utility for cosmetic applications.
To obtain ideal liquid bandage polymer materials, a series of polyurethane-urea dispersions were synthesized from 4,4 0 -diisocyanato dicyclohexylmethane (H 12 MDI) and ethylene diamine with different molar ratio of polyol blend [polyethylene glycol (PEG, M n ¼ 2000 g/ mol)/hydroxy terminated poly(dimethylsiloxane) (PDMS, M n ¼ $ 550 g/mol)] and acetone/ethanol as a solvent. The effect of PDMS content in PEG/PDMS on the viscosity, mechanical properties, water contact angle/surface energy, insolubility in water (%), water absorption (%), equilibrium water content (%), and water vapor transmission rate (g m À2 day À1) of polyurethane-urea films was investigated. As PDMS content increased, the water contact angle, insolubility in water, and tensile strength/elastic recovery of film sample increased; however, the surface energy, water absorption (%), equilibrium water content (%), and water vapor transmission rate (g m À2 day À1) of film sample decreased. By a wound-healing evaluation using a full-thickness rat model experiment, it was found that a wound covered with a typical polyurethane-urea liquid bandage film (PD2 sample) was filled with new epithelium without any significant adverse reactions. These results suggest that the polyurethane-urea-based liquid bandages (samples: PD2 and PD3) prepared in this study may have high potential as new wound dressing materials, which provide and maintain the adequate wet environment required to prevent scab formation and dehydration of the wound bed.
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