Microneedles (MNs) with unique three-dimensional stereochemical structures are suitable candidates for tissue fixation and drug delivery. However, existing hydrogel MNs exhibit poor mechanical properties after swelling and require complex preparation procedures, impeding their practical application. Hence, we engineered chitosan fiber-reinforced silk fibroin MN patches containing epigallocatechin gallate (SCEMN). A formic acid–calcium chloride system was introduced to fabricate hydrogel MNs with excellent inherent adhesion, and the incorporation of chitosan fiber as a reinforcing material enhanced mechanical strength and viscosity, thereby increasing the physical interlocking with tissue and the ability to maintain shape. The SCEMN with a lower insertion force firmly adhered to porcine skin, with a maximum detachment force of 11.98 N/cm2. Additionally, SCEMN has excellent antioxidant and antibacterial properties, facilitates macrophage polarization from M1 to M2, and demonstrates superior performance in vivo for diabetic wound repair compared with the commercial product Tegaderm™. This study represents the first trial of fiber-reinforced hydrogel MNs for robust tissue adhesion. Our findings underscore the significance of this innovative approach for advancing MN technology to enhance tissue adhesion and accelerate wound healing.

Type I interferon (IFN) induction is a critical component of innate immune response to viral and bacterial infection, including S. aureus, but whether it activates the signaling in macrophages and the regulation mechanisms is less well understood. Here we show that S. aureus infection promoted the IFN-β mRNA expression and stimulator of IFN genes (STING)/TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)-dependent production of IFN-β. Infection with S. aureus induced caspase recruitment domain and membrane-associated guanylate kinase-like domain protein 3 (CARMA3) expression at both the mRNA and protein levels. The heat-killed bacteria failed to trigger IRF3 phosphorylation and upregulation of CARMA3 expression. However, overexpression of CARMA3 did not affect phosphorylation of TBK1 or IRF3 in RAW264.7 cells, J774A.1 macrophages, and mouse embryonic fibroblast (MEF) cells. In conclusion, S. aureus infection induces STING/TBK1/IRF3-mediated IFN-β production in a CARMA3-independent manner.

Cartilage tissue engineering is emerging as a therapeutic approach for the repair and regeneration of cartilage tissue defects resulting from trauma and disease. It is still essential to explore approaches that employ combinations of ideal seed cells, biomaterials, and growth factors to repair defect areas because cartilage lacks spontaneous regenerative capabilities and traditional treatments do not fully satisfy clinical requirements. The purpose of this review is to summarize key advances in this area with an emphasis on adult stem cells because these cells possess a self-renewal ability and the potential for multi-directional differentiation when cultured under appropriate conditions, such as chondrocyte differentiation to synthesize cartilage-specific matrix proteins. Additionally, hydrogels and their synergistic action with growth factors to co-regulate cell behaviors and cartilage regeneration will be addressed. Hydrogels are three-dimensional water-swollen networks that provide a unique microenvironment to promote the chondrogenic phenotype by encapsulating cells as a functional cartilage substitute in a defect area. Ultimately, this review presents the prospect of combining adult stem cells, hydrogels, and growth factors using interdisciplinary approaches that may lead to significant breakthroughs in cartilage regeneration in the future.