Facile Size Tunable Skin-Adaptive Patch for Accelerating Wound Healing.

Owing to the moist and curved interfaces of skin wounds, enhancing the adhesiveness while maintaining delivery efficacy of biomolecules has drawn significant attention in advanced wound dressings. Despite tremendous trials to load biomolecules with sound adhesiveness, the complicated fabricating processes and abnormal allergic responses that are attributed to chemical moiety-based adhesives remain as major problems. To this end, in this study a one-step fabrication process is developed to manufacture microstructures with both a therapeutic (cylindrical structure for embossed structure human adipose-derived stem cell sheet, ESS) and an adhesive part (octopi-inspired structure of adhesive, OIA), which ESOIA is called.

Large-scale smart bioreactor with fully integrated wireless multivariate sensors and electronics for long-term in situ monitoring of stem cell culture.

Achieving large-scale, cost-effective, and reproducible manufacturing of stem cells with the existing devices is challenging. Traditional single-use cell-bag bioreactors, limited by their rigid and single-point sensors, struggle with accuracy and scalability for high-quality cell manufacturing. Here, we introduce a smart bioreactor system that enables multi-spatial sensing for real-time, wireless culture monitoring.

In vivo shear wave elasticity imaging for assessment of diaphragm function in muscular dystrophy.

Duchenne muscular dystrophy (DMD) causes patients to suffer from ambulatory disability and cardiorespiratory failure, the latter of which leads to premature death. Due to its role in respiration, the diaphragm is an important muscle for study. A common method for evaluating diaphragm function is ex vivo force testing, which only allows for an end point measurement.

Three-Dimensional Cell Culture System for Tendon Tissue Engineering.

Tendon, connective tissue between bone and muscle has unique component of the musculoskeletal system. It plays important role for transporting mechanical stress from muscle to bone and enabling locomotive motion of the body. There are some restoration capacities in the tendon tissue, but the injured tendons are not completely regenerated after acute and chronic tendon injury.

Visible light-curable methacrylated glycol chitosan hydrogel patches for prenatal closure of fetal myelomeningocele.

In this study, we prepared visible light-curable methacrylated glycol chitosan (MGC) hydrogel patches for the prenatal treatment of fetal myelomeningocele (MMC) and investigated their feasibility using a retinoic acid-induced fetal MMC rat model. 4, 5, and 6 w/v% of MGC were selected as candidate precursor solutions, and photo-cured for 20 s, because the resulting hydrogels were found to possess concentration dependent tunable mechanical properties and structural morphologies. Moreover, these materials exhibited no foreign body reactions with good adhesive properties in animal studies.

Development of a stem cell spheroid-laden patch with high retention at skin wound site.

Mesenchymal stem cells such as human adipose tissue-derived stem cells (hADSCs) have been used as a representative therapeutic agent for tissue regeneration because of their high proliferation and paracrine factor-secreting abilities. However, certain points regarding conventional ADSC delivery systems, such as low cell density, secreted cytokine levels, and cell viability, still need to be addressed for treating severe wounds. In this study, we developed a three-dimensional (3D) cavity-structured stem cell-laden system for overdense delivery of cells into severe wound sites.

Nanomaterial for Skeletal Muscle Regeneration.

Skeletal muscle has an innate regenerative capacity to restore their structure and function following acute damages and injuries. However, in congenital muscular dystrophies, large volumetric muscle loss, cachexia, or aging, the declined regenerative capacity of skeletal muscle results in muscle wasting and functional impairment. Recent studies indicate that muscle mass and function are closely correlated with morbidity and mortality due to the large volume and location of skeletal muscle.

Area light source-triggered latent angiogenic molecular mechanisms intensify therapeutic efficacy of adult stem cells.

Light-based therapy such as photobiomodulation (PBM) reportedly produces beneficial physiological effects in cells and tissues. However, most reports have focused on the immediate and instant effects of light. Considering the physiological effects of natural light exposure in living organisms, the latent reaction period after irradiation should be deliberated.

Phototoxicity-free blue light for enhancing therapeutic angiogenic efficacy of stem cells.

Low-level light therapy (LLLT) is a safe and noninvasive technique that has drawn attention as a new therapeutic method to treat various diseases. However, little is known so far about the effect of blue light for LLLT due to the generation of reactive oxygen species (ROS) that can cause cell damage. We introduced a blue organic light-emitting diode (bOLED) as a safe and effective light source that could generate a low amount of heat and luminance compared to conventional light sources (e.

Delivery of a spheroids-incorporated human dermal fibroblast sheet increases angiogenesis and M2 polarization for wound healing.

Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the short doubling times of fibroblasts together with their immunomodulatory properties.

Development of pH-Responsive Polymer Coating as an Alternative to Enzyme-Based Stem Cell Dissociation for Cell Therapy.

Cell therapy usually accompanies cell detachment as an essential process in cell culture and cell collection for transplantation. However, conventional methods based on enzymatic cell detachment can cause cellular damage including cell death and senescence during the routine cell detaching step due to an inappropriate handing. The aim of the current study is to apply the pH-responsive degradation property of poly (amino ester) to the surface of a cell culture dish to provide a simple and easy alternative method for cell detachment that can substitute the conventional enzyme treatment.

Regulation of intracellular transition metal ion level with a pH-sensitive inorganic nanocluster to improve therapeutic angiogenesis by enriching conditioned medium retrieved from human adipose derived stem cells.

Cell therapy based on human adipose derived stem cells (hADSCs) is a known potential therapeutic approach to induce angiogenesis in ischemic diseases. However, the therapeutic efficacy of direct hADSC injection is limited by a low cell viability and poor cell engraftment after administration. To improve the outcomes of this kind of approach, various types of nanoparticles have been utilized to improve the therapeutic efficacy of hADSC transplantation.

Endosome-triggered ion-releasing nanoparticles as therapeutics to enhance the angiogenic efficacy of human mesenchymal stem cells.

Here, we report that Fe ions delivered into human mesenchymal stem cells (hMSCs) by bioreducible metal nanoparticles (NPs) enhance their angiogenic and cell-homing efficacy by controlling ion-triggered intracellular reactive oxygen species (ROS) and improve cell migration, while reducing cytotoxicity. Endosome-triggered iron-ion-releasing nanoparticles (ETIN) were designed to be low-pH responsive to take advantage of the low-pH conditions (4-5) of endosomes for in situ iron-ion release. Due to the different redox potentials of Fe and Au, only Fe could be ionized and released from our novel ETIN, while Au remained intact after ETIN endocytosis.

Synthesis of Sub 3 nm-Sized Uniform Magnetite Nanoparticles Using Reverse Micelle Method for Biomedical Application.

We report a synthetic method for small and uniform FeO (magnetite) nanoparticles under mild conditions. Spherical sub-3 nm-sized magnetite nanoparticles were prepared via reverse micelles composed of oleylamine, F127, xylene, and water for the reaction of iron(III) stearate with hydrazine at a reaction temperature of 90 °C in air atmosphere. These synthesized magnetite nanoparticles exhibited good size uniformity.

Cardiac-mimetic cell-culture system for direct cardiac reprogramming.

Cardiovascular diseases often cause substantial heart damage and even heart failure due to the limited regenerative capacity of adult cardiomyocytes. The direct cardiac reprogramming of fibroblasts could be a promising therapeutic option for these patients. Although exogenous transcriptional factors can induce direct cardiac reprogramming, the reprogramming efficiency is too low to be used clinically.

Enhancing the Wound Healing Effect of Conditioned Medium Collected from Mesenchymal Stem Cells with High Passage Number Using Bioreducible Nanoparticles.

Injecting human mesenchymal stem cells (hMSCs) at wound sites is known to have a therapeutic effect; however, hMSCs have several limitations, such as low viability and poor engraftment after injection, as well as a potential risk of oncogenesis. The use of a conditioned medium (CM) was suggested as an alternative method for treating various wounds instead of direct hMSC administration. In addition to not having the adverse effects associated with hMSCs, a CM can be easily mass produced and can be stored for long-term, thereby making it useful for clinical applications.

Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord-Derived Mesenchymal Stem Cells.

Background And Objectives: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM).

Methods And Results: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest.

FGF-17 from Hypoxic Human Wharton's Jelly-Derived Mesenchymal Stem Cells Is Responsible for Maintenance of Cell Proliferation at Late Passages.

Background And Objectives: Although it is well known that hypoxic culture conditions enhance proliferation of human mesenchymal stem cells, the exact mechanism is not fully understood. In this study, we investigated the effect of fibroblast growth factor (FGF)-17 from hypoxic human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on cell proliferation at late passages.

Methods And Results: hWJ-MSCs were cultured in -MEM medium supplemented with 10% fetal bovine serum (FBS) in normoxic (21% O) and hypoxic (1% O) conditions.

Metabolites can regulate stem cell behavior through the STAT3/AKT pathway in a similar trend to that under hypoxic conditions.

Stem cell therapy has long been considered a promising mode of treatment for many incurable diseases. Human mesenchymal stem cells (hMSCs) have provided the most promising results to date for regenerative medicine. Nevertheless, due to several obstacles such as difficulty in sourcing and characterizing hMSCs, they remain largely unavailable for clinical use.

A Disposable Photovoltaic Patch Controlling Cellular Microenvironment for Wound Healing.

Electrical stimulation (ES) is known to affect the wound healing process by modulating skin cell behaviors. However, the conventional clinical devices that can generate ES for promoting wound healing require patient hospitalization due to large-scale of the extracorporeal devices. Herein, we introduce a disposable photovoltaic patch that can be applied to skin wound sites to control cellular microenvironment for promoting wound healing by generating ES.

M1 Macrophage-Derived Nanovesicles Potentiate the Anticancer Efficacy of Immune Checkpoint Inhibitors.

Cancer immunotherapy modulates immune cells to induce antitumor immune responses. Tumors employ immune checkpoints to evade immune cell attacks. Immune checkpoint inhibitors such as anti-PD-L1 antibody (aPD-L1), which is being used clinically for cancer treatments, can block immune checkpoints so that the immune system can attack tumors.

An Injectable Decellularized Matrix That Improves Mesenchymal Stem Cell Engraftment for Therapeutic Angiogenesis.

Stem cell therapy has great potential for the treatment of ischemic diseases, but poor engraftment of implanted stem cells limits the therapeutic efficacy. Here, we developed an approximately 80 μm injectable decellularized matrix (IDM) to increase the angiogenic efficacy of mesenchymal stem cells by improving the engraftment of the stem cells implanted in to an ischemic tissue. Adhesion of human adipose tissue-derived stem cells (hADSCs) to the IDM enhanced the cell viability and upregulated angiogenic factors in vitro under either cell adhesion-suppressive conditions or hypoxic conditions, which simulated the microenvironment of ischemic tissues.

Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair.

Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach.

Efficient Direct Lineage Reprogramming of Fibroblasts into Induced Cardiomyocytes Using Nanotopographical Cues.

Induced cardiomyocytes (iCMs) generated via direct lineage reprogramming offer a novel therapeutic target for the study and treatment of cardiac diseases. However, the efficiency of iCM generation is significantly low for therapeutic applications. Here, we show an efficient direct conversion of somatic fibroblasts into iCMs using nanotopographic cues.