Bioactive sucralfate-based microneedles promote wound healing through reprogramming macrophages and protecting endogenous growth factors.

Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound environments. Here, we present a two-stage strategy using bioactive sucralfate-based microneedle (SUC-MN) for delivering interleukin-4 (IL-4) to accelerate wound healing.

Attenuating Epithelial-to-Mesenchymal Transition in Cancer through Angiopoietin-Like 4 Inhibition in a 3D Tumor Microenvironment Model.

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastatic cancer progression, and current research, which relies heavily on 2D monolayer cultures, falls short in recapitulating the complexity of a 3D tumor microenvironment. To address this limitation, a transcriptomic meta-analysis is conducted on diverse cancer types undergoing EMT in 2D and 3D cultures. It is found that mechanotransduction is elevated in 3D cultures and is further intensified during EMT, but not during 2D EMT.

Mechano-Activated Cell Therapy for Accelerated Diabetic Wound Healing.

Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. A powerful platform technology combining magneto-responsive hydrogel, cells, and wireless magneto-induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing.

Dynamic Stimulations with Bioengineered Extracellular Matrix-Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy.

Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.

Dynamic Magneto-Softening of 3D Hydrogel Reverses Malignant Transformation of Cancer Cells and Enhances Drug Efficacy.

High extracellular matrix stiffness is a prominent feature of malignant tumors associated with poor clinical prognosis. To elucidate mechanistic connections between increased matrix stiffness and tumor progression, a variety of hydrogel scaffolds with dynamic changes in stiffness have been developed. These approaches, however, are not biocompatible at high temperature, strong irradiation, and acidic/basic pH, often lack reversibility (can only stiffen and not soften), and do not allow study on the same cell population longitudinally.

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy.

Bone marrow-derived mesenchymal stem cell (MSC) is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties. Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers, but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected .

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system.

The lymph node (LN) is a vital organ of the lymphatic and immune system that enables timely detection, response, and clearance of harmful substances from the body. Each LN comprises of distinct substructures, which host a plethora of immune cell types working in tandem to coordinate complex innate and adaptive immune responses. An improved understanding of LN biology could facilitate treatment in LN-associated pathologies and immunotherapeutic interventions, yet at present, animal models, which often have poor physiological relevance, are the most popular experimental platforms.

Materials for Improving Immune Cell Transfection.

Chimeric antigen receptor T cell (CAR-T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks like viral transgene integration and excessive biological perturbations.

Thermoresponsive Chitosan/DOPA-Based Hydrogel as an Injectable Therapy Approach for Tissue-Adhesion and Hemostasis.

Chitosan (CS) hydrogels are widely used in wound hemostatic agents due to their superior biocompatibility, biodegradability, and hemostatic effect. However, most of them fail to achieve great hemostatic effect because of poor adhesion to bleeding tissues. Also, the conventional implantation surgery of hemostatic hydrogels to internal bleeding wounds may cause secondary trauma to the human body.

Stack-Based Hydrogels with Mechanical Enhancement, High Stability, Self-Healing Property, and Thermoplasticity from Poly(l-glutamic acid) and Ureido-Pyrimidinone.

Supramolecular hydrogels formed by noncovalent bonds are attractive "smart" materials, which can rapidly respond to external stimuli. However, only a handful of supramolecular hydrogels is applicable in tissue engineering, due to the instability and poor mechanical strength of noncovalent cross-linking hydrogels. Thus, a rigid and stable supramolecular hydrogel has been developed based on poly(l-glutamic acid) and 2-ureido-4[1]pyrimidinones (UPy), and the UPy stacks are noncovalent cross-linking interactions.

Biodegradable High-Strength Hydrogels with Injectable Performance Based on Poly(l-Glutamic Acid) and Gellan Gum.

Currently, biodegradable hydrogels are one of the most promising materials in tissue engineering. From the perspective of clinical needs, hydrogels with high strength and minimally invasive implantation are preferred for the reconstruction of load-bearing tissues. In this work, a biodegradable, high-strength, and injectable hydrogel was developed by one-step photo-cross-linking of two biomacromolecules, polyethylene glycol acrylated poly(l-glutamic acid) (PLGA-APEG) and methacrylated gellan gum (GG-MA).