A retrospective study of inpatients diagnosed with degloving skin and soft tissue injuries.

The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.

Stem cell-based therapeutic strategies for rotator cuff tendinopathy.

Rotator cuff tendinopathy is a common musculoskeletal disorder that imposes significant health and economic burden. Stem cell therapy has brought hope for tendon healing in patients with final stage rotator cuff tendinopathy. Some clinical trials have confirmed the effectiveness of stem cell therapy for rotator cuff tendinopathy, but its application has not been promoted and approved. There are still many issues that should be solved prior to using stem cell therapy in clinical applications. The optimal source and dose of stem cells for rotator cuff tendinopathy should be determined. We also proposed novel prospective approaches that can overcome cell population heterogeneity and standardize patient types for stem cell applications. The translational potential of this article: This review explores the optimal sources of stem cells for rotator cuff tendinopathy and the principles for selecting stem cell dosages. Key strategies are provided for stem cell population standardization and recipient selection.

Animal model for tendinopathy.

Background: Tendinopathy is a common motor system disease that leads to pain and reduced function. Despite its prevalence, our mechanistic understanding is incomplete, leading to limited efficacy of treatment options. Animal models contribute significantly to our understanding of tendinopathy and some therapeutic options. However, the inadequacies of animal models are also evident, largely due to differences in anatomical structure and the complexity of human tendinopathy. Different animal models reproduce different aspects of human tendinopathy and are therefore suitable for different scenarios. This review aims to summarize the existing animal models of tendinopathy and to determine the situations in which each model is appropriate for use, including exploring disease mechanisms and evaluating therapeutic effects. Methods: We reviewed relevant literature in the PubMed database from January 2000 to December 2022 using the specific terms ((tendinopathy) OR (tendinitis)) AND (model) AND ((mice) OR (rat) OR (rabbit) OR (lapin) OR (dog) OR (canine) OR (sheep) OR (goat) OR (horse) OR (equine) OR (pig) OR (swine) OR (primate)). This review summarized different methods for establishing animal models of tendinopathy and classified them according to the pathogenesis they simulate. We then discussed the advantages and disadvantages of each model, and based on this, identified the situations in which each model was suitable for application. Results: For studies that aim to study the pathophysiology of tendinopathy, naturally occurring models, treadmill models, subacromial impingement models and metabolic models are ideal. They are closest to the natural process of tendinopathy in humans. For studies that aim to evaluate the efficacy of possible treatments, the selection should be made according to the pathogenesis simulated by the modeling method. Existing tendinopathy models can be classified into six types according to the pathogenesis they simulate: extracellular matrix synthesis-decomposition imbalance, inflammation, oxidative stress, metabolic disorder, traumatism and mechanical load. Conclusions: The critical factor affecting the translational value of research results is whether the selected model is matched with the research purpose. There is no single optimal model for inducing tendinopathy, and researchers must select the model that is most appropriate for the study they are conducting. The translational potential of this article: The critical factor affecting the translational value of research results is whether the animal model used is compatible with the research purpose. This paper provides a rationale and practical guide for the establishment and selection of animal models of tendinopathy, which is helpful to improve the clinical transformation ability of existing models and develop new models.

Single cell analysis reveals inhibition of angiogenesis attenuates the progression of heterotopic ossification in Mkx-/- mice.

Tendon heterotopic ossification (HO) is characterized by bone formation inside tendon tissue, which severely debilitates people in their daily life. Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis. Here, we investigate the pathological mechanism and propose a potential treatment method for HO. Immunofluorescence assays showed that the Mohawk (MKX) expression level was decreased in human tendon HO tissue, coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx-/- mice. Single-cell RNA sequencing analyses of wild-type and Mkx-/- tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx-/- tendon cells. Single-cell analysis revealed that the gene expression program of angiogenesis, which is strongly associated with bone formation, was activated in all cell types during HO. Moreover, inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO. These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.

Extracellular Matrix Remodeling in Stem Cell Culture: A Potential Target for Regulating Stem Cell Function.

Stem cells (SCs) hold great potential for regenerative medicine, tissue engineering, and cell therapy. The clinical applications of SCs require both high quality and quantity of transplantable cells. However, during conventional in vitro expansion, SCs tend to lose properties that make them amenable for cell therapies. Extracellular matrix (ECM) serves an essential regulatory part in the growth, differentiation, and homeostasis of all cells in vivo, and when signals are transmitted to cells, they do not respond passively. Many cell types can remodel pericellular matrix to meet their specific needs. This reciprocal cell-ECM interaction is crucial for the conservation of cell and tissue functions and homeostasis. In vitro ECM remodeling also plays a key role in regulating the lineage fate of SCs. A deeper understanding of in vitro ECM remodeling may provide new perspectives for the maintenance of SC function. In this review, we critically examined three ways that cells can be used to influence the pericellular matrix: (1) exerting tensile force on the ECM, (2) secreting a variety of ECM proteins, and (3) degrading the surrounding matrix, and its impact on SC lineage fate. Finally, we describe the deficiencies of current studies and what needs to be done next to further understand the role of ECM remodeling in ex vivo SC cultures. Impact statement The effect of extracellular matrix (ECM) remodeling on physiological activities and disease progression has been extensively studied, but its effect on in vitro stem cell (SC) culture has received insufficient attention. More and more research has shown that in vitro ECM remodeling is critical for maintaining SCs function. This review will highlight how cells remodel ECM and the significance of ECM remodeling in ex vivo SC culture, as well as summarize the shortcomings of current research and what needs to be done next to further our understanding of the role of ECM remodeling in ex vivo SC culture.

Cell-subpopulation alteration and FGF7 activation regulate the function of tendon stem/progenitor cells in 3D microenvironment revealed by single-cell analysis.

Three dimensional (3D) microenvironments more accurately replicate native microenvironments for stem cell maintenance and function compared with two dimensional (2D) microenvironments. However, the molecular mechanisms by which 3D microenvironments regulate stem cell function remain largely unexplored at the single-cell level. Here, using a single-cell analysis and functional analysis, we found not all cell-subpopulations respond to 3D microenvironments based on a systematically 3D gelatin microcarrier culture system we developed for the expansion and function maintenance of hTSPCs. 3D microenvironments alter the cell-subpopulation distribution of human tendon stem/progenitor cells (hTSPCs) by improving the proportion of ICAM1+ITGB8+ and FGF7+CYGB+ subpopulations. We also revealed the activated FGF7 signaling in the two subpopulations is responsible for the enhanced tenogenesis of hTSPCs through cell-cell interactions. The hTSPCs cultured in 3D niche with a specific cell-subpopulation structure exhibited superior stem-cell characteristics and functions both in vitro and in vivo. Together, our study demonstrates that 3D microenvironments can regulate stem-cell function by modulating the critical cell subpopulation and identifies FGF7 as a novel regulator for tenogenic differentiation and tendon regeneration.

Biomimetic Joint Paint for Efficient Cartilage Repair by Simultaneously Regulating Cartilage Degeneration and Regeneration in Pigs.

Irregular partial-thickness cartilage defect is a common pathogenesis of osteoarthritis (OA) with no available treatment in clinical practice. Currently, cartilage tissue engineering is only suitable for a limited area of full-thickness cartilage defect. Here, we design a biomimetic joint paint for the intractable partial-thickness cartilage defect repair. The joint paint, composed of a bridging layer of chondroitin sulfate and a surface layer of gelatin methacrylate with hyaluronic acid, can quickly and tightly adhere to the cartilage defect by light activation. Being treated by the joint paint, the group of rabbit and pig models with partial-thickness cartilage defects showed a restoration of a smooth cartilage surface and the preservation of normal glycosaminoglycan content, whereas the untreated control group exhibited serious progressive OA development. This paint treatment functions by prohibiting chondrocyte apoptosis, maintaining chondrocyte phenotype, and preserving the content of glycosaminoglycan in the partial-thickness cartilage defects. These findings illustrated that the biomimetic joint paint is an effective and revolutionary therapeutics for the patients with noncurable partial-thickness cartilage defects.

Single-cell RNA-seq reveals functionally distinct biomaterial degradation-related macrophage populations.

Macrophages play crucial roles in host tissue reaction to biomaterials upon implantation in vivo. However, the complexity of biomaterial degradation-related macrophage subpopulations that accumulate around the implanted biomaterials in situ is not fully understood. Here, using single cell RNA-seq, we analyze the transcriptome profiles of the various cell types around the scaffold to map the scaffold-induced reaction, in an unbiased approach. This enables mapping of all biomaterial degradation-associated cells at high resolution, revealing distinct subpopulations of tissue-resident macrophages as the major cellular sources of biomaterial degradation in situ. We also find that scaffold architecture can affect the mechanotransduction and catabolic activity of specific material degradation-related macrophage subpopulations in an Itgav-Mapk1-Stat3 dependent manner, eventually leading to differences in scaffold degradation rate in vivo. Our work dissects unanticipated aspects of the cellular and molecular basis of biomaterial degradation at the single-cell level, and provides a conceptual framework for developing functional tissue engineering scaffolds in future.

Early-Stage Primary Anti-inflammatory Therapy Enhances the Regenerative Efficacy of Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model.

BACKGROUND: Tendinopathy is a pervasive clinical problem that afflicts both athletes and the general public. Although the inflammatory changes in tendinopathy are well characterized, how the therapeutic effects of platelet-rich plasma (PRP) on tendinopathy are being modulated by the inflammatory environment is not well defined. PURPOSE/HYPOTHESIS: In this study, we aimed to compare the therapeutic effects of PRP alone versus a combination of PRP with a primary glucocorticoid (GC) injection at the early stage of tendinopathy. We hypothesized that PRP treatment could promote better tendon regeneration through the suppression of inflammation with GC. STUDY DESIGN: Controlled laboratory study. METHODS: The gene expression profile of tendon stem/progenitor cells (TSPCs) cultured with PRP was analyzed with RNA sequencing. To evaluate the cell viability, senescence, and apoptosis of TSPCs under different conditions, TSPCs were treated with 0.1 mg/mL triamcinolone acetonide (TA) and/or 10% PRP in an IL1B-induced inflammatory environment. To further verify the effects of the sequential therapy of GCs and PRP, an early tendinopathy animal model was established through a local injection of collagenase in the rabbit Achilles tendon. The tendinopathy model was then treated with isopycnic normal saline (NS group), TA (TA group), PRP (PRP group), or TA and PRP successively (TA+PRP group). At 8 weeks after treatment, the tendons were assessed with magnetic resonance imaging (MRI), histological examination, transmission electron microscopy (TEM), and mechanical testing. RESULTS: Gene Ontology enrichment analysis indicated that PRP treatment of TPSCs induced an inflammatory response, regulated cell migration, and remodeled the extracellular matrix. Compared with the sole use of PRP, successive treatment with TA followed by PRP yielded similar results in cell viability and senescence but less cell apoptosis in vitro. In vivo experiments demonstrated that the TA+PRP group achieved significantly better tendon regeneration, as confirmed by MRI, histological examination, TEM, and mechanical testing. CONCLUSION: This study showed that the primary use of GCs did not exert any obvious deleterious side effects on the treated tendon but instead enhanced the regenerative effects of PRP in early inflammatory tendinopathy. CLINICAL RELEVANCE: The sequential therapy of GCs followed by PRP provides a promising treatment strategy for tendinopathy in clinical practice. PRP combined with the primary use of GCs appears to promote tendon regeneration in early inflammatory tendinopathy.

An Off-the-Shelf Tissue Engineered Cartilage Composed of Optimally Sized Pellets of Cartilage Progenitor/Stem Cells.

Articular cartilage focal lesion remains an intractable challenge in sports medicine, and autologous chondrocytes' implantation (ACI) is one of the most commonly utilized treatment modality for this ailment. However, the current ACI technique requires two surgical steps which increases patients' morbidity and incurs additional medical costs. In the present study, we developed a one-step cryopreserved off-the-shelf ACI tissue-engineered (TE) cartilage by seeding pellets of spheroidal cartilage stem/progenitor cells (CSPCs) on a silk scaffold. The pellets were developed through a hanging-drop method, and the incubation time of 1 day could efficiently produce spheroidal pellets without any adverse influence on the cell activity. The pellet size was also optimized. Under chondrogenic induction, pellets consisting of 40 000 CSPCs were found to exhibit the most abundant cartilage matrix deposition and the highest mRNA expression levels of SOX9, aggrecan, and COL2A1, as compared with pellets consisting of 10 000, 100 000, or 200 000 CSPCs. Scaffolds seeded with CSPCs pellets containing 40 000 cells could be preserved in liquid nitrogen with the viability, migration, and chondrogenic ability remaining unaffected for as long as 3 months. When implanted in a rat trochlear cartilage defect model for 3 months, the ready-to-use, cryopreserved TE cartilage yielded fully cartilage reconstruction, which was comparable with the uncryopreserved control. Hence, our study provided preliminary data that our off-the-shell TE cartilage with optimally sized CSPCs pellets seeded within silk scaffolds exhibited strong cartilage repair capacity, which provided a convenient and promising one-step surgical approach to ACI.

Non-muscle myosin II knockdown improves survival and therapeutic effects of implanted bone marrow-derived mesenchymal stem cells in lipopolysaccharide-induced acute lung injury.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to have some beneficial effects in acute lung injury (ALI), but the therapeutic effects are limited due to apoptosis or necrosis after transplantation into injured lungs. Here, we aim to explore whether Non-muscle myosin II (NM-II) knockdown could enhance BMSCs survival and improve therapeutic effects in ALI. METHODS: MSCs, isolated from rat bone marrow, were transfected with the small interfering RNA (siRNA) targeted to NM-II mRNA by a lentivirus vector. Rats were equally randomized to four groups: the control group was given normal saline via tail vein; the other three groups underwent intratracheal lipopolysaccharide (LPS) instillation followed by administration with either normal saline, BMSCs transduced with lentivirus-enhanced green fluorescent protein (eGFP) empty vector, or BMSCs transduced with lentivirus-eGFP NM-II siRNA. Hematoxylin and eosin staining was used to evaluate lung histopathologic changes and Masson trichrome staining was used to assess lung fibrosis. The myeloperoxidase activity was also tested in lung tissues. The mRNA expression of inflammatory cytokines in lung tissues was determined via quantitative reverse transcription PCR. Sex-determining region of the Y chromosome gene expression was measured by fluorescence in situ hybridization (FISH) assay. The expression of self-renewal activity and apoptosis-associated proteins were measured by Western blot. RESULTS: Transplantation of NM-II siRNA-modified BMSCs could improve histopathological morphology, decrease inflammatory infiltrates, down-regulate the expression levels of inflammatory cytokines, and reduce pulmonary interstitial edema. NM-II siRNA-modified BMSCs showed antifibrotic properties and alleviated the degrees of pulmonary fibrosis induced by endotoxin. In addition, NM-II knockdown BMSCs showed slightly better therapeutic effect on lung inflammation when compared with control BMSCs. The beneficial effects of NM-II siRNA-modified BMSCs may be attributed to enhanced self-renewal activity and decreased apoptosis. CONCLUSIONS: NM-II knockdown could inhibit the apoptosis of implanted BMSCs in lung tissues and improve its self-renewal activity. NM-II siRNA-modified BMSCs have a slightly enhanced ability to attenuate lung injury after LPS challenge.

Four-Objective Optimizations for an Improved Irreversible Closed Modified Simple Brayton Cycle.

An improved irreversible closed modified simple Brayton cycle model with one isothermal heating process is established in this paper by using finite time thermodynamics. The heat reservoirs are variable-temperature ones. The irreversible losses in the compressor, turbine, and heat exchangers are considered. Firstly, the cycle performance is optimized by taking four performance indicators, including the dimensionless power output, thermal efficiency, dimensionless power density, and dimensionless ecological function, as the optimization objectives. The impacts of the irreversible losses on the optimization results are analyzed. The results indicate that four objective functions increase as the compressor and turbine efficiencies increase. The influences of the latter efficiency on the cycle performances are more significant than those of the former efficiency. Then, the NSGA-II algorithm is applied for multi-objective optimization, and three different decision methods are used to select the optimal solution from the Pareto frontier. The results show that the dimensionless power density and dimensionless ecological function compromise dimensionless power output and thermal efficiency. The corresponding deviation index of the Shannon Entropy method is equal to the corresponding deviation index of the maximum ecological function.

3D printing of chemical-empowered tendon stem/progenitor cells for functional tissue repair.

Tendon injuries are the leading cause of chronic debilitation to patients. Tendon stem/progenitor cells (TSPCs) are potential seed cells for tendon tissue engineering and regeneration, but TSPCs are prone to lose their distinct phenotype in vitro and specific differentiation into the tenocyte lineage is challenging. Utilizing small molecules in an ex vivo culture system may be a promising solution and can significantly improve the therapeutic applications of these cells. Here, by using an image-based, high-throughput screening platform on small molecule libraries, this study established an effective stepwise culture strategy for TSPCs application. The study formulated a cocktail of small molecules which effected proliferation, tenogenesis initiation and maturation phases, and significantly upregulated expression of various tendon-related genes and proteins in TSPCs, which were demonstrated by high-throughput PCR, ScxGFP reporter assay and immunocytochemistry. Furthermore, by combining small molecule-based culture system with 3D printing technology, we embedded living, chemical-empowered TSPCs within a biocompatible hydrogel to engineer tendon grafts, and verified their enhanced ability in promoting functional tendon repair and regeneration both in vivo and in situ. The stepwise culture system for TSPCs and construction of engineered tendon grafts can not only serve as a platform for further studies of underlying molecular mechanisms of tenogenic differentiation, but also provide a new strategy for tissue engineering and development of novel therapeutics for clinical applications.

Minimum Entropy Generation Rate and Maximum Yield Optimization of Sulfuric Acid Decomposition Process Using NSGA-II.

Based on the theory of finite-time thermodynamics (FTT), the effects of three design parameters, that is, inlet temperature, inlet pressure, and inlet total mole flow rate, of a tubular plug-flow sulfuric acid decomposition reactor on the total entropy generation rate (EGR) and SO2 yield are analyzed firstly. One can find that when the three design parameters are taken as optimization variables, the minimum total EGR and the maximum SO2 yield of the reference reactor restrict each other, i.e., the two different performance objectives cannot achieve the corresponding extremum values at the same time. Then, the second-generation non-dominated solution sequencing genetic algorithm (NSGA-II) is further used to pursue the minimum total EGR and the maximum SO2 yield of the reference reactor by taking the three parameters as optimization design variables. After the multi-objective optimization, the reference reactor can be Pareto improved, and the total EGR can be reduced by 9% and the SO2 yield can be increased by 14% compared to those of the reference reactor. The obtained results could provide certain theoretical guidance for the optimal design of actual sulfuric acid decomposition reactors.

Targeted pathological collagen delivery of sustained-release rapamycin to prevent heterotopic ossification.

Heterotopic ossification (HO) in connective tissues like tendons and ligaments severely damages tissue structure. The pathogenesis of HO remains unclear but may involve mTOR. The results presented here indicate that tendon stem/progenitor cells do not undergo osteochondrogenic differentiation when mTOR signaling is inactivated by gene knockout or rapamycin (RAPA) treatment. Meanwhile, it is necessary to deliver RAPA to the injured sites and avoid disturbing the normal tendon. A RAPA delivery system, developed using collagen hybrid peptide (CHP) to modify the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, targeted RAPA specifically to pathological tendon collagen. The CHP-PLGA-RAPA nanoparticles showed excellent pathological collagen affinity, sustained-release ability, and bioactivity. In a mouse model of tendon HO, CHP-PLGA-RAPA nanoparticles specifically bound to pathological tendon and strongly suppressed HO progression. The mTOR signaling pathway appears to be a viable therapeutic target for tendon HO, and CHP-PLGA nanoparticles may be valuable for the treatment of tendon-related diseases.

Characterization and Comparison of Postnatal Rat Meniscus Stem Cells at Different Developmental Stages.

Meniscus-derived stem cells (MeSCs) are a potential cell source for meniscus tissue engineering. The stark morphological and structural changes of meniscus tissue during development indicate the complexity of MeSCs at different tissue regions and stages of development. In this study, we characterized and compared postnatal rat meniscus tissue and MeSCs at different tissue regions and stages of development. We observed that the rat meniscus tissue exhibited marked changes in tissue morphology during development, with day 7 being the most representative time point of different developmental stages. All rat MeSCs displayed typical stem cell characteristics. Rat MeSCs derived from day 7 inner meniscus tissue exhibited the highest self-renewal capacity, cell proliferation, differentiation potential toward various mesenchymal lineage and the highest expression levels of chondrogenic genes and proteins. Transplantation of rat MeSCs derived from day 7 inner meniscus tissue promoted neo-tissue formation and effectively protected joint surface cartilage in vivo. Our results demonstrated for the first time that rat MeSCs are not necessarily better at earlier developmental stages, and that rat MeSCs derived from day 7 inner meniscus tissue may be a superior cell source for effective meniscus regeneration and articular cartilage protection. This information could make a significant contribution to human meniscus tissue engineering in the future. Stem Cells Translational Medicine 2019;8:1318&1329.

Controlled-release curcumin attenuates progression of tendon ectopic calcification by regulating the differentiation of tendon stem/progenitor cells.

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.

Pharmacological Inhibition of Rac1 Activity Prevents Pathological Calcification and Enhances Tendon Regeneration.

Tendinopathy is a common disease, which is characterized by pain, swelling, and dysfunction. At the late stage of tendinopathy, pathological changes may occur, such as tendon calcification. Previously, we have shown that in situ tendon stem/progenitor cells (TSPCs) underwent osteogenesis in the inflammatory niche in diseased tendons. In this study, we demonstrate that this process is accompanied by the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling. A specific inhibitor NSC23766 significantly downregulated catabolic factors and calcification-related genes and rescued the tenogenesis gene expression of TSPCs under the influence of Interleukin (IL)-1ß in vitro. For in vivo evaluation, we further developed a drug delivery system to encapsulate Rac1 inhibitor NSC23766. Chitosan/ß-glycerophosphate hydrogel encapsulated NSC23766 effectively impeded tendon calcification and enhanced tendon regeneration in rat Achilles tendinosis. Our findings indicated that inhibiting Rac1 signaling could act as an effective intervention for tendon pathological calcification and promote tendon regeneration, thus providing a new therapeutic strategy.

Knitted Silk-Collagen Scaffold Incorporated with Ligament Stem/Progenitor Cells Sheet for Anterior Cruciate Ligament Reconstruction and Osteoarthritis Prevention.

Current surgical management of anterior cruciate ligament (ACL) rupture still remains an intractable challenge in ACL regeneration due to the weak self-healing capability of ACL. Inadequate cell numbers and vascularization within the articular cavity contribute mainly to the poor prognosis. This time, we fabricated a new tissue engineering scaffold by adding ligament stem/progenitor cell (LSPC) sheets to our previous knitted silk-collagen sponge scaffold, which overcame these limitations by providing sufficient numbers of seed cells and a natural extracellular matrix to facilitate regeneration. LSPCs display excellent proliferation and multilineage differentiation capacity. Upon ectopic implantation, the knitted silk-collagen sponge scaffold incorporated with an LSPC sheet exhibited less immune cells but more fibroblast-like cells, deposited ECM and neovascularization, and better tissue ingrowth. In a rabbit model, we excised the ACL and performed a reconstructive surgery with our scaffold. Increased expression of ligament-specific genes and better collagen fibril formation could be observed after orthotopic transplantation. After 6 months, the LSPC sheet group showed better results on ligament regeneration and ligament-bone healing. Furthermore, no obvious cartilage and meniscus degeneration were observed at 6 months postoperation. In conclusion, these results indicated that the new tissue engineering scaffold can promote ACL regeneration and slow down the progression of osteoarthritis, thus suggesting its high clinical potential as an ideal graft in ACL reconstruction.

A collagen-coated sponge silk scaffold for functional meniscus regeneration.

Tissue engineering is a promising solution for meniscal regeneration after meniscectomy. However, in situ reconstruction still poses a formidable challenge due to multifunctional roles of the meniscus in the knee. In this study, we fabricate a silk sponge from 9% (w/v) silk fibroin solution through freeze drying and then coat its internal space and external surface with collagen sponge. Subsequently, various characteristics of the silk-collagen scaffold are evaluated, and cytocompatibility of the construct is assessed in vitro and subcutaneously. The efficacy of this composite scaffold for meniscal regeneration is evaluated through meniscus reconstruction in a rabbit meniscectomy model. It is found that the internally coated collagen sponge enhances the cytocompatibility of the silk sponge, and the external layer of collagen sponge significantly improves the initial frictional property. Additionally, the silk-collagen composite group shows more tissue ingrowth and less cartilage wear than the pure silk sponge group at 3 months postimplantation in situ. These findings thus demonstrate that the composite scaffold had less damage to the joint surface than the silk alone through promoting functional meniscal regeneration after meniscectomy, which indicates its clinical potential in meniscus reconstruction.