Type H vessels-a bridge connecting subchondral bone remodelling and articular cartilage degeneration in osteoarthritis development.

Recent studies have shed light on the cellular and molecular mechanisms that link subchondral bone remodelling and angiogenesis in knee osteoarthritis (OA). Type H vessels are a newly identified bone blood vessel characterized by high expression of CD31 and endomucin that are coupled with osteogenesis. Factors including mechanical loading, TGF-ß1, platelet-derived growth factor type BB, the osteoprotegerin-RANK ligand-RANK system, osteopontin, mechanistic target of rapamycin, VEGF, stromal cell-derived factor l and prostaglandin E2 participate in the formation of type H vessels in osteoarthritic subchondral bone. In this review, we summarize the current understanding of type H vessels in knee OA, as well as the signalling pathways involved and potential therapeutic medicines. In future, the pathogenesis of knee OA could be further clarified by connecting type H vessels and the design of new disease-modifying osteoarthritis drugs. However, further experiments are needed to determine the upstream signals regulating type H vessel formation in osteoarthritic subchondral bone.

Minimally invasive transforaminal lumbar interbody fusion versus oblique lateral interbody fusion for lumbar degenerative disease: a meta-analysis.

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 < 0.0001), whereas improvement of VAS for back pain (P = 0.08) and ODI (P = 0.98) as well as JOABPEQ effectiveness rate (P = 0.18) were similar in the two groups. Radiographically, OLIF was more effective in restoring disc height (P = 0.01) and equivalent in improving the disc angle (P = 0.18) and lumbar lordosis (P = 0.48) compared with MIS-TLIF. The fusion rate (P = 0.11) was similar in both groups, while the subsidence was more severe in the MIS-TLIF group (P < 0.00001). CONCLUSIONS: The above evidence suggests that OLIF is associated with a shorter operation time (with supplementary fixation in the prone position) and less intraoperative blood loss than MIS-TLIF and can lead to better leg pain alleviation, disc height restoration and subsidence resistance. No differences regarding back pain relief, functional recovery, complications, disc angle restoration, lumbar lordosis restoration and fusion rate were found. However, due to the limited number of studies, our results should be confirmed with high-level studies to fully compare the therapeutic efficacy of MIS-TLIF and OLIF. TRIAL REGISTRATION: PROSPERO ID:  CRD42020201903 .

Copper promotes the migration of bone marrow mesenchymal stem cells via Rnd3-dependent cytoskeleton remodeling.

The motility of mesenchymal stem cells (MSCs) is highly related to their homing in vivo, a critical issue in regenerative medicine. Our previous study indicated copper (Cu) might promote the recruitment of endogenous MSCs in canine esophagus defect model. In this study, we investigated the effect of Cu on the motility of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism in vitro. Cu supplementation could enhance the motility of BMSCs, and upregulate the expression of hypoxia-inducible factor 1α (Hif1α) at the protein level, and upregulate the expression of rho family GTPase 3 (Rnd3) at messenger RNA and protein level. When Hif1α was silenced by small interfering RNA (siRNA), Cu-induced Rnd3 upregulation was blocked. When Rnd3 was silenced by siRNA, the motility of BMSCs was decreased with or without Cu supplementation, and Cu-induced cytoskeleton remodeling was neutralized. Furthermore, overexpression of Rnd3 also increased the motility of BMSCs and induced cytoskeleton remodeling. Overall, our results demonstrated that Cu enhanced BMSCs migration through, at least in part, cytoskeleton remodeling via Hif1α-dependent upregulation of Rnd3. This study provided an insight into the mechanism of the effect of Cu on the motility of BMSCs, and a theoretical foundation of applying Cu to improve the recruitment of BMSCs in tissue engineering and cytotherapy.

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

High-resolution vasomotion analysis reveals novel arteriole physiological features and progressive modulation of cerebral vascular networks by stroke.

Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca2+ dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca2+ and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca2+ activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.

Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p.

Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant in vivo vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486-5p in H-exo inhibit SERPINE1 activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.

Extracellular Vesicles from Urine-Derived Stem Cell for Tissue Engineering and Regenerative Medicine.

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

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.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy.

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.

Establishment and comparison of different procedures for modeling intrauterine adhesion in rats: A preliminary study.

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.

Tissue engineered esophagus by mesenchymal stem cell seeding for esophageal repair in a canine model.

PURPOSE: Acellular porcine small intestinal submucosa (SIS) has been successfully used for esophagoplasty in dogs. However, this has not led to complete epithelialization and muscular regeneration. We undertook the present study to assess the effect of tissue-engineered esophagus generated by seeding bone marrow mesenchymal stem cells (BMSCs) onto an SIS scaffold (BMSCs-SIS) in a canine model. METHODS: We cultured, passaged, and measured autologous BMSCs and myoblasts with cell proliferation and immunohistochemical assays. We labeled the third passage of BMSCs with PKH-26, a fluorescent dye, before seeded it onto the SIS. We resected canine cervical esophagus to generate a defect 5 cm in length and 50% in circumference, which we repaired with BMSCs-SIS or SIS alone. RESULTS: Four weeks later, barium esophagram demonstrated that esophageal lumen surface of the patch graft was smoother in the BMSCs-SIS group compared with the SIS group. Histological examination suggested a strong similarity between BMSCs and esophageal myoblasts in terms of morphology and function. Although both BMSCs-SIS and SIS repaired the esophageal defects, we noted complete re-epithelialization with almost no inflammation only in the former group. By 12 wk after the surgery, we observed long bundles of skeletal muscles only in the BMSCs-SIS group, where the microvessel density was also much greater. CONCLUSIONS: Bone marrow mesenchymal stem cells on an SIS scaffold can promote re-epithelialization, revascularization, and muscular regeneration. This approach may provide an attractive option for esophageal regeneration.

Results of Medial Patellofemoral Ligament Reconstruction with and without Tibial Tubercle Transfer in Patellar Instability: A Systematic Review and Meta-Analysis.

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.

A Modified Small Intestinal Submucosa Patch with Multifunction to Promote Scarless Repair and Reinvigoration of Urethra.

To reconstruct and restore the functions of the male urethra is a challenging task for urologists. The acellular matrix graft currently used in the clinics is mono-functional and may cause a series of complications including stricture, fibrosis, and stone formation. As a result, such graft materials cannot meet the increasing demand for multifunctionality in the field of urethral tissue engineering. In this context, a multifunctional urethral patch is designed for the repair of urethral defects by mixing protocatechualdehyde (PCA) with small intestinal submucosa (SIS) under an alkalin condition to allow cross linking. As shown, the PCA/SIS patch possesses excellent biocompatibility, antioxidant activity, and anti-inflammatory property. More importantly, this patch can remarkably promote the adhesion, proliferation, and directional extension of rabbit bladder epithelial mucous cells (R-EMCs) as well as rabbit bladder smooth muscle cells (R-SMCs), and upregulate the expression of cytokeratin in the EMCs and contractile protein in the SMCs in vitro. In vivo experiments also confirm that the PCA/SIS patch can significantly enhance scarless repair of urethral defects in rabbits by facilitating smooth muscle regeneration, reducing excessive collagen deposition, and accelerating re-epithelialization and neovascularization. Taken together, the newly developed multifunctional PCA/SIS patch provides a promising candidate for urethral regeneration.

Recent progress in bone-repair strategies in diabetic conditions.

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.

A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability, extracellular matrix-inducing bioactivity and function preservation.

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.

An Acquired Anterior Glottic Web Model by Heat Injury with a Laryngoscopic Approach in a Rabbit.

Acquired anterior glottic webs (AGW) can lead to abnormally elevated phonatory pitch, dysphonia, and airway obstruction requiring urgent intervention. In this study, we construct a novel AGW rabbit model using heat injury by a laryngoscopic way. A primary study was conducted to identify the injury depth in rabbits' vocal folds (VFs) by graded heat energy, and the heat energy for the incurrence of epithelial layer, lamina propria, and muscular layer (ML) injury was 25, 30 and 35 W, respectively. Then, four different models were designed based on the depth and degree of the injury to determine the optimal procedure for AGW formation. Morphological features, vibratory capacity, and histopathologic features of the AGW were correspondingly evaluated. The procedure for conferring the heat injury to the depth of ML and the extent of anterior commissure and middle part of bilateral VFs showed the highest success rate of AGW formation (95%, 19/20). For its low cost, effectiveness, and stability for AGW formation, the heat injury rabbit model with a laryngoscopic approach may provide a new platform for testing novel anti-adhesion materials and bioengineered therapies. Impact Statement Tissue engineering based on biomaterials has been a very hot research field and may be introduced to prevent the acquired anterior glottic web (AGW) formation. However, lacking a widely recognized animal model for AGW has limited the trial of anti-adhesion materials in the larynx. In this study, we have developed a novel rabbit model for AGW formation by conferring a heat injury under a laryngoscope; this model is cheap, effective, and stable for the anti-adhesion materials and bioengineered therapies. Thus, this research would arouse crucial interest and be widely employed.

Polyphenolic-modified cellulose acetate membrane for bone regeneration through immunomodulation.

To enhance the bioactivity of cellulosic derivatives has become an important strategy to promote their value for clinical applications. Herein, protocatechualdehyde (PCA), a polyphenolic molecule, was used to modify a cellulose acetate (CA) membrane by combining with metal ions to confer an immunomodulatory activity. The PCA-modified CA membrane has shown a significant radical scavenging activity, thereby suppressed the inflammatory response and created a favorable immune microenvironment for osteogenesis and mineralization. Moreover, addition of metal ions could further stimulate the osteogenic differentiation of stem cells and accelerate bone regeneration both in vitro and in vivo. This study may provide a strategy to promote the immunomodulatory activity of cellulose-based biomaterials for bone regeneration.

Bioactive ECM-Loaded SIS Generated by the Optimized Decellularization Process Exhibits Skin Wound Healing Ability in Type I Diabetic Rats.

Patients with diabetes have 15-25% chance for developing diabetic ulcers as a severe complication and formidable challenge for clinicians. Conventional treatment for diabetic ulcers is to surgically remove the necrotic skin, clean the wound, and cover it with skin flaps. However, skin flap often has a limited efficacy, and its acquisition requires a second surgery, which may bring additional risk for the patient. Skin tissue engineering has brought a new solution for diabetic ulcers. Herein, we have developed a bioactive patch through a compound culture and the optimized decellularization strategy. The patch was prepared from porcine small intestinal submucosa (SIS) and modified by an extracellular matrix (ECM) derived from urine-derived stem cells (USCs), which have low immunogenicity while retaining cytokines for angiogenesis and tissue regeneration. The protocol included the optimization of the decellularization time and the establishment of the methods. Furthermore, the in vitro mechanism of wound healing ability of the patch was investigated, and its feasibility for skin wound healing was assessed through an antishrinkage full-thickness skin defect model in type I diabetic rats. As shown, the patch displayed comparable effectiveness to the USCs-loaded SIS. Our findings suggested that this optimized decellularization protocol may provide a strategy for cell-loaded scaffolds that require the removal of cellular material while retaining sufficient bioactive components in the ECM for further applications.