No abstract

Mesenchymal stem cells (MSCs) are an ideal seed cell for tissue engineering and stem cell transplantation. MSCs combined with biological scaffolds play an important role in promoting the repair of cutaneous wound. However, direct administration of MSCs is challenging for MSCs survival and integration into tissues. Providing MSCs with a biocompatible scaffold can improve MSCs survival, but the effect of Gelatin Methacrylate (GelMA) loaded MSCs from umbilical cord mesenchymal stem cells (UC-MSCs) in wound healing remains unknown. Here, we investigated the ability of GelMA with UC-MSCs complexes to promote migration and proliferation and the effect on wound healing in mouse models. We discovered that UC-MSCs attached to GelMA and promoted the proliferation and migration of fibroblasts. Both UC-MSCs and UC-MSCs-derived extracellular vesicles accelerated wound healing. MSC+GMs application decreased expression of transforming growth factor-β (TGF-β) and Type III collagen (Col3) in vivo, leading to new collagen deposition and angiogenesis, and accelerate wound healing and skin tissue regeneration. Taken together, these findings indicate MSC + GMs can promote wound healing by regulating wound healing-related factors in the paracrine. Therefore, our research proves that GelMA is an ideal scaffold for the top management of UC-MSCs in wound healing medical practice.

Hydroxy-α-sanshool (HAS), extracted from Zanthoxylum piperitum , is commonly used in oral surgery to relief pain. However, the application of HAS is limited in clinical practice due to its poor stability. This study focuses on the design of a novel nano-formulation delivery system for HAS to improve its stability and local anesthetic effect. Hydroxy-α-sanshool loaded nanostructured lipid carriers (HAS-NLCs) were prepared by melting emulsification and ultra-sonication using monostearate (GMS) and oleic acid (OA) as lipid carriers, and poloxamer-188 (F68) as a stabilizer. Besides, the formulation was optimized by response surface methodology (RSM). Then, the best formulation was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), drug loading (DL%), differential scanning calorimetry (DSC), and morphology (transmission electron microscopy, TEM). The obtained HAS-NLCs were homogeneous, near spherical particles with high DL% capacity. The stability of HAS-NLCs against oxygen, light, and heat was greatly improved over 10.79 times, 3.25 times, and 2.09 times, respectively, compared to free HAS. In addition, HAS-NLCs could exhibit sustained release in 24 h following a double-phase kinetics model in vitro release study. Finally, HAS-NLCs had excellent anesthetic effect at low dose in formalin test compared with free HAS and lidocaine, which indicated HAS-NLCs were a potential local anesthesia formulation in practice.

Background: Hydroxy-α-Sanshool (HAS) possesses various pharmacological properties, such as analgesia and regulating gastrointestinal function. However, the low oral bioavailability of HAS has limited its oral delivery in clinical application. Methods and Results: To enhance its oral bioavailability, a nanocomposite delivery system based on chitosan (CH, as the polycation) and sodium alginate (SA, as the polyanion) was prepared using a layer-by-layer coating technique. The morphology, thermal behavior and Fourier transform infrared spectrum (FTIR) showed that the obtained sodium alginate/chitosan-coated HAS-loaded liposomes (SA/CH-HAS-LIP) with core-shell structures have been successfully covered with polymers. When compared with HAS-loaded liposomes (HAS-LIP), SA/CH-HAS-LIP displayed obvious pH sensitivity and a sustained-release behavior in in vitro studies, which fitted well to Weibull model. In vivo, the half-life of HAS from SA/CH-HAS-LIP remarkably extended after oral administration compared to the free drug. Additionally, it allowed a 4.6-fold and 4.2-fold increase in oral bioavailability, respectively, compared with free HAS and HAS-LIP. Conclusions: SA/CH-HAS-LIP could be a promising release vehicle for the oral delivery of HAS to increase its oral bioavailability.