Nontyphoidal salmonella septic arthritis in A patient with systemic lupus erythematosus: A case report.

We report a case of septic arthritis in a 43-year-old female patient. Despite initial treatment with ceftriaxone for Nontyphoidal Salmonella based on blood and joint fluid culture results, the shoulder joint pain worsened. Suspected systemic lupus erythematosus associated synovitis did not respond to immunosuppressive therapy including methylprednisolone, hydroxychloroquine and methotrexate. Subsequent radiograph revealed a shoulder joint abscess, leading to arthroscopic joint debridement. Ceftriaxone was administered post-operatively until analgesic efficacy was attained. This case highlights the significance of accurate diagnosis and appropriate treatment for nontyphoidal Salmonella septic arthritis.

Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel.

Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.

3D bioprinted mesenchymal stromal cells in skin wound repair.

Skin tissue regeneration and repair is a complex process involving multiple cell types, and current therapies are limited to promoting skin wound healing. Mesenchymal stromal cells (MSCs) have been proven to enhance skin tissue repair through their multidifferentiation and paracrine effects. However, there are still difficulties, such as the limited proliferative potential and the biological processes that need to be strengthened for MSCs in wound healing. Recently, three-dimensional (3D) bioprinting has been applied as a promising technology for tissue regeneration. 3D-bioprinted MSCs could maintain a better cell ability for proliferation and expression of biological factors to promote skin wound healing. It has been reported that 3D-bioprinted MSCs could enhance skin tissue repair through anti-inflammatory, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling. In this review, we will discuss the progress on the effect of MSCs and 3D bioprinting on the treatment of skin tissue regeneration, as well as the perspective and limitations of current research.

3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing.

Severe burns are challenging to heal and result in significant death throughout the world. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising treatment for full-thickness burn healing but are impeded by their low viability and efficiency after grafting in vivo. Nitric oxide (NO) is beneficial in promoting stem cell bioactivity, but whether it can function effectively in vivo is still largely unknown. In this study, we bioprinted an efficient biological scaffold loaded with ADSCs and NO (3D-ADSCs/NO) to evaluate its biological efficacy in promoting severe burn wound healing. The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting. Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs). Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition. Notably, immunohistochemistry of CD31 suggested an increase in neovascularization, supported by the upregulation of vascular endothelial growth factor (VEGF) mRNA in ADSCs in the 3D biosystem. These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway. This scaffold may be considered a promising strategy for healing severe burns.

Hyaluronic acid-curcumin conjugate suppresses the fibrotic functions of myofibroblasts from contractive joint by the PTGER2 demethylation.

Joint contracture is a fibrotic complication induced by joint immobilization and trauma, which is characterized as excessive myofibroblast proliferation in joint capsule. The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction. Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro, but the major challenge is the low aqueous solubility and biological activity of curcumin. In this study, hyaluronic acid-curcumin (HA-Cur) conjugate was synthesized to suppress myofibroblasts in joint contracture. Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-ß (TGF-ß). The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (PCR), methylation-specific PCR, western blot, transwell migration assay and proliferation assay. Results showed that 30 µM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2 (PTGER2) and inhibiting TGF-ß signaling. This may provide a mechanism for the treatment of joint contracture, and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.

Autograft microskin combined with adipose-derived stem cell enhances wound healing in a full-thickness skin defect mouse model.

OBJECTIVE: Autograft microskin transplantation has been widely used as a skin graft therapy in full-thickness skin defect. However, skin grafting failure can lead to a pathological delay wound healing due to a poor vascularization bed. Considering the active role of adipose-derived stem cell (ADSC) in promoting angiogenesis, we intend to investigate the efficacy of autograft microskin combined with ADSC transplantation for facilitating wound healing in a full-thickness skin defect mouse model. MATERIAL AND METHODS: An in vivo full-thickness skin defect mouse model was used to evaluate the contribution of transplantation microskin and ADSC in wound healing. The angiogenesis was detected by immunohistochemistry staining. In vitro paracrine signaling pathway was evaluated by protein array and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. RESULTS: Co-transplantation of microskin and ADSC potentiated the wound healing with better epithelization, smaller scar thickness, and higher angiogenesis (CD31) in the subcutaneous layer. We found both EGF and VEGF cytokines were secreted by microskin in vitro. Additionally, secretome proteomic analysis in a co-culture system of microskin and ADSC revealed that ADSC could secrete a wide range of important molecules to form a reacting network with microskin, including VEGF, IL-6, EGF, uPAR, MCP-3, G-CSF, and Tie-2, which most likely supported the angiogenesis effect as observed. CONCLUSION: Overall, we concluded that the use of ADSC partially modulates microskin function and enhances wound healing by promoting angiogenesis in a full-thickness skin defect mouse model.

A Mini-Invasive Internal Fixation Technique for Studying Immobilization-Induced Knee Flexion Contracture in Rats.

Joint contracture, resulting from a prolonged joint immobilization, is a common complication in orthopedics. Currently, utilizing an internal fixation to restrict knee joint mobility is a widely accepted model to generate experimental contracture. However, implanting application will inevitably cause surgical trauma to the animals. Aiming to develop a less invasive approach, we combined a muscle-gap separation modus with a previously reported mini-incision skill during the surgical procedure: Two mini skin incisions were made on the lateral thigh and leg, followed by performing muscle-gap separation to expose the bone surface. The rat knee joint was gradually immobilized by a preconstructed internal fixation at approximately 135° knee flexion without interfering essential nerves or blood vessels. As expected, this simple technique permits rapid postoperative rehabilitation in animals. The correct position of the internal fixation was confirmed by an x-ray or micro-CT scanning analysis. The range of motion was significantly restricted in the immobilized knee joint than that observed in the contralateral knee joint demonstrating the effectiveness of this model. Besides, histological analysis revealed the development of fibrous deposition and adhesion in the posterior-superior knee joint capsule over time. Thus, this mini-invasive model may be suitable for mimicking the development of immobilized knee joint contracture.