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Uncontrolled hemorrhage remains the leading cause of death in clinical and emergency care, posing a major threat to human life. To achieve effective bleeding control, many hemostatic materials have emerged. Among them, nature-derived biopolymers occupy an important position due to the excellent inherent biocompatibility, biodegradability and bioactivity. Additionally, sponges have been widely used in clinical and daily life because of their rapid blood absorption. Therefore, we provide the overview focusing on the latest advances and smart designs of biopolymer-based hemostatic sponge. Starting from the component, the applications of polysaccharide and polypeptide in hemostasis are systematically introduced, and the unique bioactivities such as antibacterial, antioxidant and immunomodulation are also concerned. From the perspective of sponge structure, different preparation processes can obtain unique physical properties and structures, which will affect the material properties such as hemostasis, antibacterial and tissue repair. Notably, as development frontier, the multi-functions of hemostatic materials is summarized, mainly including enhanced coagulation, antibacterial, avoiding tumor recurrence, promoting tissue repair, and hemorrhage monitoring. Finally, the challenges facing the development of biopolymer-based hemostatic sponges are emphasized, and future directions for in vivo biosafety, emerging materials, multiple application scenarios and translational research are proposed.

Abstract Research on treating knee osteoarthritis (KOA) is becoming more challenging due to a growing number of younger patients being affected. The pathogenesis of KOA is complex for being a multifactorial disease affecting the entire joint, with remodeling of subchondral bone playing a key role in the degeneration of the overlying cartilage. Therefore, this study constructed a bipedal postmenopausal KOA mouse model to better understand how the interplay between subchondral bone remodeling and cartilage degeneration contributes to KOA development. A single-cell atlas of the osteochondral composite tissue was established. Furthermore, three novel subtypes of chondrocytes, including Smoc2 + angiogenic chondrocytes, Angptl7 + angiogenic chondrocytes, and Col1a1 + osteogenic chondrocytes, were identified in femoral condyles of KOA mice. In addition, the Angptl7 + chondrocytes promoted angiogenesis in the subchondral bone of KOA mice by interacting with endothelial cells via the FGF2-FGFR2 signaling pathway. The number of H-type vessels was increased in the subchondral bone, recruiting osteoprogenitor cells and facilitating osteogenesis in KOA mice. Sparc + osteoblasts have negatively regulated bone mineralization and osteoblastic differentiation, aggravated the pathological remodeling of subchondral bone, and promoted the progression of KOA. The above findings have offered new targets and opened up an avenue for the therapeutic intervention of KOA.

Matrix metalloproteinases (MMPs), coupled with other proteinases and glycanases, can degrade proteoglycans, collagens, and other extracellular matrix (ECM) components in inflammatory and non-inflammatory arthritis, making them important pathogenic molecules and ideal disease indicators and pharmaceutical intervention triggers. For MMP responsiveness, MMP-sensitive peptides (MSPs) are among the most easily synthesized and cost-effective substrates, with free terminal amine and/or carboxyl groups extensively employed in multiple designs. We hereby provide a comprehensive review over the mechanisms and advances in MSP applications for the management of arthritis. These applications include early and precise diagnosis of MMP activity via fluorescence probe technologies; acting as nanodrug carriers to enable on-demand drug release triggered by pathological microenvironments; and facilitating cartilage engineering through MMP-mediated degradation, which promotes cell migration, matrix synthesis, and tissue integration. Specifically, the ultra-sensitive MSP diagnostic probes could significantly advance the early diagnosis and detection of osteoarthritis (OA), while MSP-based drug carriers for rheumatoid arthritis (RA) can intelligently release anti-inflammatory drugs effectively during flare-ups, or even before symptoms manifest. The continuous progress in MSP development may acceleratedly lead to novel management regimens for arthropathy in the future.

Abstract Background The persistently rising complication, pseudotumor, after hip arthroplasty required surgeons’ vigilance. Although the remaining controversial relationship between metal ions and pseudotumor, metal ion detection had been widely employed in clinic. The aim of this study is to evaluate the correlation between metal ions and pseudotumor, as well as the effectiveness of metal ion analysis in the screening and diagnosis of pseudotumor through systematic review and meta-analysis. Methods The Medline and Embase databases were searched for studies evaluating metal ions and patients with pseudotumors after hip arthroplasty. A systematic review of risk ratio and diagnostic performance for metal ions was conducted. Results Seven studies were included in the systematic review. The mean Methodological Index for Non-Randomized Studies (MINORS) score of the included studies was 19 (range, 14 to 22). Pooled risk ratio (RR) value was 2.01(95% CI: 1.25–3.24; P = 0.004) for cobalt ions level and 1.44 (95% CI: 1.10–1.88; P = 0.008) for chromium ions level. The pooled sensitivity, specificity and the area under the curve (AUC) for cobalt and chromium ions were determined to be 0.59, 0.82, 0.73 and 0.34, 0.82, 0.56, respectively. Conclusions The metal ions level has a low diagnostic value. It is of certain value for confirmation, but should not be used as a routine screening indicator. The diagnostic value of cobalt ions is higher than that of chromium. Level of Evidence: Diagnostic Level IV.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for “cell-free therapy” in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

The optimal surgical intervention for lateral patellar instability remains a topic of controversy despite satisfactory clinical outcomes and low re‐dislocation rates reported in numerous studies following medial patellofemoral ligament reconstruction (MPFLR) with and without tibial tubercle transfer (TTT). The purpose of this systematic review and meta‐analysis is to investigate the hypothesis that combining MPFLR with TTT provides reduced complication rates and improved clinical outcomes to isolated MPFLR in patients with lateral patellar instability. We conducted a comprehensive systematic review and meta‐analysis of comparative trials involving MPFLR with and without TTT, sourcing data from PubMed, the Cochrane Library, Embase, and Web of Science. The primary clinical outcomes analyzed included the Kujala score, the Lysholm score, complication rates, and the Caton–Deschamps index (CDI). Random or fixed effects were used for the meta‐analysis. Postoperatively, there were no significant differences observed in the Kujala and Lysholm scores between MPFLR and MPFLR + TTT (p = 0.053). At the final follow‐up, the CDI had decreased 0.015 (95% CI −0.044, 0.013; p = 0.289) points in the MPFLR group, with no statistical significance. In contrast, the MPFLR + TTT group demonstrated a significant decrease of 0.207 (95% CI −0.240, −0.174; p = 0.000) points in CDI. Notably, the complication rate was higher in the MPFLR + TTT group compared to the MPFLR‐only group (RR = 2.472; 95% CI 1.638, 3.731; p = 0.000). Both MPFLR and MPFLR + TTT procedures yield significant improvements in the Kujala and Lysholm scores. However, the MPFLR + TTT approach results in an apparent improvement in CDI and corrects patellar maltracking, particularly in cases involving high tibial tuberosity‐trochlear groove (TT‐TG) (>20 mm) or patella alta (CDI > 1.2), while MPFLR alone cannot. It is essential to consider the higher complication rate of MPFLR + TTT, which suggests that MPFLR alone may be sufficient for patients without high TT‐TG or patella alta.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on ''click'' chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

The establishment of a stable animal model for intrauterine adhesion (IUA) can significantly enhance research on the pathogenesis and pathological changes of this disease, as well as on the development of innovative therapeutic approaches. In this study, three different modeling methods, including phenol mucilage combined mechanical scraping, ethanol combined mechanical scraping and ethanol modeling alone were designed. The morphological characteristics of the models were evaluated. The underlying mechanisms and fertility capacity of the ethanol modeling group were analyzed and compared to those of the sham surgery group. All three methods resulted in severe intrauterine adhesions, with ethanol being identified as a reliable modeling agent and was subsequently subjected to further evaluation. Immunohistochemistry and RT-PCR results indicated that the ethanol modeling group exhibited an increase in the degree of fibrosis and inflammation, as well as a significant reduction in endometrial thickness, gland number, vascularization, and endometrial receptivity, ultimately resulting in the loss of fertility capacity. The aforementioned findings indicate that the intrauterine perfusion of 95 % ethanol is efficacious in inducing the development of intrauterine adhesions in rats. Given its cost-effectiveness, efficacy, and stability in IUA formation, the use of 95 % ethanol intrauterine perfusion may serve as a novel platform for evaluating innovative anti-adhesion materials and bioengineered therapies.

Abstract Rapid and effective control of non‐compressible massive hemorrhage poses a great challenge in first‐aid and clinical settings. Herein, a biopolymer‐based powder is developed for the control of non‐compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross‐linking based on “click” chemistry and Schiff base reaction upon contact with the blood, leading to rapid self‐gelling. It also exhibits robust tissue adhesion through covalent/non‐covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non‐compressible hemorrhage.

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency. However, the inadequate durability, deficient pro-secretion of extracellular matrix (ECM) and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect. Herein, a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism (photo-triggered and dynamic covalent bonds). Owing to its characteristic networks, the synergistic effect of the hydrogel for vocal folds (VFs) vibration and phonation is adequately demonstrated. Notably, owing to its inherent bioactivity of polysaccharides, the hydrogel could significantly enhance the secretion of major components (type I/III collagen and elastin) in the lamina propria of the VFs both in vivo and in vitro. In a rabbit model for glottic insufficiency, the optimized hydrogel (C1A1) has demonstrated a durability far superior to that of the commercially made hyaluronic acid (HA) Gel. More importantly, owing to the ECM-inducing bioactivity, the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel, and were similar to those of the normal VFs. Taken together, through a simple-yet-effective strategy, the novel hydrogel has demonstrated outstanding durability, ECM-inducing bioactivity and physiological function preservation, therefore has an appealing clinical value for treating glottic insufficiency.

Abstract Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.

Bone regeneration following trauma, tumor resection, infection, or congenital disease is challenging. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. It can result in complications affecting multiple systems including the musculoskeletal system. The increased number of diabetes-related fractures poses a great challenge to clinical specialties, particularly orthopedics and dentistry. Various pathological factors underlying DM may directly impair the process of bone regeneration, leading to delayed or even non-union of fractures. This review summarizes the mechanisms by which DM hampers bone regeneration, including immune abnormalities, inflammation, reactive oxygen species (ROS) accumulation, vascular system damage, insulin/insulin-like growth factor (IGF) deficiency, hyperglycemia, and the production of advanced glycation end products (AGEs). Based on published data, it also summarizes bone repair strategies in diabetic conditions, which include immune regulation, inhibition of inflammation, reduction of oxidative stress, promotion of angiogenesis, restoration of stem cell mobilization, and promotion of osteogenic differentiation, in addition to the challenges and future prospects of such approaches.

Objective It is unclear whether idiopathic osteonecrosis of the femoral head (ONFH) is associated with borderline developmental dysplasia of the hip (BDDH). This study aimed to compare the incidence of BDDH between patients with idiopathic ONFH and matched control subjects and determine the influence of BDDH on poor prognosis after core decompression (CD). Methods We retrospectively examined 78 consecutive patients (111 hips) with idiopathic ONFH undergoing CD and 1:2 matched with 156 control subjects (222 hips). The anteroposterior pelvic radiographs were used to measure the acetabular anatomical parameters and divide included subjects into BDDH or non‐BDDH group. The incidence of BDDH and acetabular anatomical parameters were compared between patients with idiopathic ONFH and matched controls. Clinical outcomes, such as Harris Hip Score (HHS), progression of collapse, and conversion to total hip arthroplasty (THA), were compared between patients with BDDH and without BDDH in the idiopathic ONFH group, with a mean follow‐up of 72.1 ± 36.6 months. Results Patients with idiopathic ONFH had a significantly higher incidence of BDDH than matched controls (29.7% vs 12.2%, p

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Approximately 25% of patients with congenital heart disease require implantation of patches to repair. However, most of the currently available patches are made of inert materials with unmatched electrical conductivity and mechanical properties, which may lead to an increased risk for arrhythmia and heart failure. In this study, we have developed a novel Polyurethane/Small intestinal submucosa patch (PSP) with mechanical and electrical properties similar to those of the native myocardial tissue, and assessed its feasibility for the reconstruction of right ventricular outflow tract. A right ventricular outflow tract reconstruction model was constructed in 40 rabbits. Compared with commercially available bovine pericardium patch, the PSP patch has shown better histocompatibility and biodegradability, in addition with significantly improved cardiac function. To tackle the significant fibrosis and relatively poor vascularization during tissue remodeling, we have further developed a bioactive patch by incorporating the PSP composites with urine-derived stem cells (USCs) which were pretreated with hypoxia. The results showed that the hypoxia-pretreated bioactive patch could significantly inhibit fibrosis and promote vascularization and muscularization, resulting in better right heart function. Our findings suggested that the PSP patch combined with hypoxia-pretreated USCs may provide a better strategy for the treatment of congenital heart disease.

Abstract Objective To assess the efficacy and safety of hypotensive anesthesia (HA) combined with tranexamic acid (TXA) for reducing perioperative blood loss in simultaneous bilateral total hip arthroplasty (SBTHA). Methods In this retrospective cohort study, a total of 183 eligible patients (15 females and 168 males, 44.01 ± 9.29 years old) who underwent SBTHA from January 2015 to September 2020 at our medical center were enrolled for analysis. Fifty‐nine patients received standard general anesthesia (Std‐GA group), the other 85 and 39 patients received HA with an intraoperative mean arterial pressure between 70 and 80 mmHg (70–80 HA group) and below 70 mmHg (

Vocal fold (VF) scarring is a major etiology of voice disorders and a leading cause for permanent intractable dysphonia. To date, several approaches have been used to address VF injury and scarring, which included scar excision and biomaterial injection and/or implantation. Despite the considerable research progress made in this field, these have not been established as routine clinical procedures due to various restrictions. Tissue engineered scaffolds for delivering growth factors in vivo and implementation of simultaneous delivery of multi-potent cells may achieve better outcome. In this study, we have developed Urine-derived stem cells - Small intestinal submucosa hydrogel composites (USCs@SIS), which are injectable and capable of sustaining the survival and metabolism of the USCs in the scarred VF. The three-dimensional complex showed a robust ability of anti-inflammatory polarization, neovascularization, re-epithelialization and anti-fibrosis in a rabbit model for heat-injured VFs. In vitro experiment proved that the hydrogel composites could promote polarization of M2 macrophages, tube formation by human umbilical vein endothelial cells, proliferation and migration by human bronchial epithelial cells, and suppression of differentiation of human fetal lung fibroblasts and human primary fibroblast cells of VF. Application of the USCs@SIS thereby may overcome the substantial limitations of the current strategies for scarless VF regeneration.

Abstract Intrauterine adhesion refers to endometrial repair disorders which are usually caused by uterine injury and may lead to a series of complications such as abnormal menstrual bleeding, recurrent abortion and secondary infertility. At present, therapeutic approaches to intrauterine adhesion are limited due to the lack of effective methods to promote regeneration following severe endometrial injury. Therefore, to develop new methods to prevent endometrial injury and intrauterine adhesion has become an urgent need. For severely damaged endometrium, the loss of stem cells in the endometrium may affect its regeneration. This article aimed to discuss the characteristics of various stem cells and their applications for uterine tissue regeneration.

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application.

Abstract Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi‐directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs‐based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs‐based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs‐based therapies and prospects for their optimization.

Abstract Background Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and oblique lateral interbody fusion (OLIF) are widely used in the treatment of lumbar degenerative diseases. In the present study, a meta-analysis was conducted to compare the clinical and radiographic efficacy of these two procedures. Methods A systematic literature review was performed, and the quality of retrieved studies was evaluated with the Newcastle-Ottawa Scale (NOS). Clinical outcomes, including operation time, intraoperative blood loss, improvement in Visual Analogue Scale (VAS), improvement in Oswestry Disability Index (ODI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate and complications, in addition to radiographic outcomes, including restoration of disc height, disc angle, overall lumbar lordosis, fusion rate and subsidence, were extracted and input into a fixed or random effect model to compare the efficacy of MIS-TLIF and OLIF. Results Seven qualified studies were included. Clinically, OLIF resulted in less intraoperative blood loss and shorter operation time than MIS-TLIF. Improvement of VAS for leg pain was more obvious in the OLIF group (P

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues, which has many side effects. Biomaterials such as small intestine submucosa (SIS) can provide an alternative scaffold for the repair as bladder patches. Previous studies have shown that SIS could enhance the capacity and compliance of the bladder, but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS. Procyanidins (PC), a natural bio-crosslinking agent, has shown anti-calcification, anti-inflammatory and anti-oxidation properties. More importantly, PC and SIS can crosslink through hydrogen bonds, which may endow the material with enhanced mechanical property and stabilized functionalities. In this study, various concentrations of PC-crosslinked SIS (PC-SIS) were prepared to repair the full-thickness bladder defects, with an aim to reduce complications and enhance bladder functions. In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property, ability to promote smooth muscle cell adhesion and upregulate functional genes expression. Using a rabbit model with bladder defects, we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration, in particular smooth muscle remodeling and improvement of urinary functions. The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.

Abstract Background Urine-derived stem cells (USCs) are a valuable stem cell source for tissue engineering because they can be harvested non-invasively. Small intestine submucosa (SIS) has been used as scaffolds for soft tissue repair in the clinic. However, the feasibility and efficacy of a combination of USCs and SIS for skin wound healing has not been reported. In this study, we created a tissue-engineered skin graft, termed the SIS+USC composite, and hypothesized that hypoxic preconditioning would improve its wound healing potential. Methods USCs were seeded on SIS membranes to fabricate the SIS+USC composites, which were then cultured in normoxia (21% O2) or preconditioned in hypoxia (1% O2) for 24 h, respectively. The viability and morphology of USCs, the expression of genes related to wound angiogenesis and reepithelialization, and the secretion of growth factors were determined in vitro. The wound healing ability of the SIS+USC composites was evaluated in a mouse full-thickness skin wound model. Results USCs showed good cell viability and morphology in both normoxia and hypoxic preconditioning groups. In vitro, hypoxic preconditioning enhanced not only the expression of genes related to wound angiogenesis (VEGF and Ang-2) and reepithelialization (bFGF and EGF) but also the secretion of growth factors (VEGF, EGF, and bFGF). In vivo, hypoxic preconditioning significantly improved the wound healing potential of the SIS+USC composites. It enhanced wound angiogenesis at the early stage of wound healing, promoted reepithelialization, and improved the deposition and remodeling of collagen fibers at the late stage of wound healing. Conclusions Taken together, this study shows that hypoxic preconditioning provides an easy and efficient strategy to enhance the wound healing potential of the SIS+USC composite.

Membranous extracellular matrix (ECM)-based scaffolds are one of the most promising biomaterials for skin wound healing, some of which, such as acellular dermal matrix, small intestinal submucosa, and amniotic membrane, have been clinically applied to treat chronic wounds with acceptable outcomes. Nevertheless, the wide clinical applications are always hindered by the poor mechanical properties, the uncontrollable degradation, and other factors after implantation. To highlight the feasible strategies to overcome the limitations, in this review, we first outline the current clinical use of traditional membranous ECM scaffolds for skin wound healing and briefly introduce the possible repair mechanisms; then, we discuss their potential limitations and further summarize recent advances in the scaffold modification and fabrication technologies that have been applied to engineer new ECM-based membranes. With the development of scaffold modification approaches, nanotechnology and material manufacturing techniques, various types of advanced ECM-based membranes have been reported in the literature. Importantly, they possess much better properties for skin wound healing, and would become promising candidates for future clinical translation.

The osteogenic potential of mesenchymal stromal cells (MSCs) varies among different tissue sources. Strontium enhances the osteogenic differentiation of bone marrow-derived MSCs (BM-MSCs), but whether it exerts similar effects on placental decidual basalis-derived MSCs (PDB-MSCs) remains unknown. Here, we compared the influence of strontium on the proliferation and osteogenic differentiation of human PDB- and BM-MSCs in vitro. We found that 1 mM and 10 mM strontium, but not 0.1 mM strontium, evidently promoted the proliferation of human PDB- and BM-MSCs. These doses of strontium showed a comparable alkaline phosphatase activity in both cell types, but their osteogenic gene expressions were promoted in a dose-dependent manner. Strontium at doses of 0.1 mM and 1 mM elevated several osteogenic gene expressions of PDB-MSCs, but not those of BM-MSCs at an early stage. Nevertheless, they failed to enhance the mineralization of either cell type. By contrast, 10 mM strontium facilitated the osteogenic gene expression as well as the mineralization of human PDB- and BM-MSCs. Collectively, this study demonstrated that human PDB- and BM-MSCs shared a great similarity in response to strontium, which promoted their proliferation and osteogenic differentiation in a dose-dependent manner.

Skeletal muscles have the potential to regenerate by activation of quiescent satellite cells, however, the molecular signature that governs satellite cells during muscle regeneration is not well defined. Myosin light chains (Myls) are sarcomere-related proteins as traditional regulator of muscle contraction. In this report, we studied the possible role of Myl in the proliferation of skeletal muscle-derived myoblasts. Compared to diaphragm-derived myoblasts, the extraocular muscle-derived myoblasts with lower levels of Myl proliferated faster, maintained a longer proliferation phase, and formed more final myotubes. It was found that blockading Myl with anti-Myl antibody or knockdown of Myll by siRNA targeted against Myll could enhance the myoblast proliferation and delay the differentiation of myoblasts. Our results suggested that Myl, likely Myll, can negatively affect myoblast proliferation by facilitating myoblast withdrawal from cell cycle and differentiation.