Cochlear Synaptopathy Evaluation With Electrocochleography in Patients With Hearing Difficulty in Noise Despite Normal Hearing Levels.

OBJECTIVE: This study examined patients with normal hearing thresholds who had trouble understanding speech in noise. We used electrocochleography (ECochG) to detect and compare SP/AP amplitude area ratios, a potential indicator of cochlear synaptopathy, and investigate speech perception disorder in noise. METHODS: The study included 68 people aged between 18 and 65 years, 35 patients and 33 healthy volunteers, who applied to the otorhinolaryngology clinic between November 2023 and March 2024 with a 2-month history of difficulty understanding speech in noisy environments. Everyone was given a tiptrode electrode ECochG test, and the results were compared between groups. An ECochG test was recorded with tiptrode electrodes and was performed on all participants, and the results were compared between groups. RESULTS: In the ECochG test, the summation potential/action potential (SP/AP) amplitude and area ratios of patients who had difficulty understanding speech in a noisy environment were statistically higher than those of the control group. CONCLUSION: ECochG testing may provide additional evidence to evaluate auditory nerve pathways.

Advances in Regenerative Medicine and Biomaterials.

The low regenerative potential of the human body hinders proper regeneration of dysfunctional or lost tissues and organs due to trauma, congenital defects, and diseases. Tissue or organ transplantation has hence been a major conventional option for replacing the diseased or dysfunctional body parts of the patients. In fact, a great number of patients on waiting lists would benefit tremendously if tissue and organs could be replaced with biomimetic spare parts on demand. Herein, regenerative medicine and advanced biomaterials strive to reach this distant goal. Tissue engineering aims to create new biological tissue or organ substitutes, and promote regeneration of damaged or diseased tissue and organs. This approach has been jointly evolving with the major advances in biomaterials, stem cells, and additive manufacturing technologies. In particular, three-dimensional (3D) bioprinting utilizes 3D printing to fabricate viable tissue-like structures (perhaps organs in the future) using bioinks composed of special hydrogels, cells, growth factors, and other bioactive contents. A third generation of multifunctional biomaterials could also show opportunities for building biomimetic scaffolds, upon which to regenerate stem cells in vivo. Besides, decellularization technology based on isolation of extracellular matrix of tissue and organs from their inhabiting cells is presented as an alternative to synthetic biomaterials. Today, the gained knowledge of functional microtissue engineering and biointerfaces, along with the remarkable advances in pluripotent stem cell technology, seems to be instrumental for the development of more realistic microphysiological 3D in vitro tissue models, which can be utilized for personalized disease modeling and drug development. This chapter will discuss the recent advances in the field of regenerative medicine and biomaterials, alongside challenges, limitations, and potentials of the current technologies.

Bioactive composite hydrogels as 3D mesenchymal stem cell encapsulation environment for bone tissue engineering: in vitro and in vivo studies.

Although decellularized bone matrix (DBM) has often been used in scaffold form for osteogenic applications, its use as a stem cell encapsulation matrix adaptable to surgical shaping procedures has been neglected. This study aimed to investigate the feasibility of utilizing solubilized DBM and nanohydroxyapatite (nHAp)-incorporated DBM hydrogels as encapsulation matrix for bone marrow-derived MSCs (BM-MSCs). First, DBM and DBM/nHAp hydrogels were assessed by physical, chemical, turbidimetric, thermal, and mechanical methods; then, in vitro cytocompatibility and in vitro hemocompatibility were investigated. An in vivo study was performed to evaluate the osteogenic properties of hydrogels alone or with BM-MSCs encapsulated in them. The findings revealed that hydrogels retained high levels of collagen and glycosaminoglycans after successful decellularization. They were found to be cytocompatible and hemocompatible in vitro, and were able to gel with sufficient mechanical stability at physiological temperature. BM-MSCs survived in culture for at least 2 weeks as metabolically active when encapsulated in both DBM and DBM/nHAp. Preliminary in vivo study showed that DBM-nHAp has higher osteogenicity than DBM. Moreover, BM-MSC encapsulated DMB/nHAp showed predominant bone-like tissue formation at 30 days in the rat ectopic site compared to its cell-free form.

Comparison of Limberg Flap and Karydakis Flap Repair in Pilonidal Sinus Surgery: A Prospective Case-Control Study.

Background Pilonidal sinus disease (PSD) is a chronic inflammation and infection of the sacrococcygeal region. It often affects young adult males and produces clinical findings with abscess and discharge in the sacrococcygeal region or painful sinus tract in the natal cleft. The best surgical technique for sacrococcygeal PSD is still disputed. This study aimed to compare the Karydakis flap technique (KFT) and Limberg flap technique (LFT) used in the surgical treatment of the sacrococcygeal pilonidal sinus. Methodology A total of 140 patients diagnosed with pilonidal sinus between 2010 and 2012 were included in the study. The patients were divided into two groups, namely, LFT (n = 73) and KFT (n = 67). Preoperative findings of the patients, surgical findings, and short and long-term postoperative findings were recorded and statistically compared. Results Regarding cosmetic results, the Karydakis flap was better than the Limberg flap with a faster return to normal life. There was no statistical difference between the two groups concerning wound dehiscence, postoperative visual analog scale scores, seroma formation, and recurrence. Conclusions Considering the faster return to normal life and greater cosmetic satisfaction of the patients, the KFT should be chosen instead of the LFT as the standard technique in pilonidal sinus surgery.

Rectus sheath hematoma as a revisited and rare cause of abdominal pain?

OBJECTIVES: Rectus sheath hematoma is the accumulation of blood within rectus abdominis muscle. The aim of this study was to investigate the clinical presentation, diagnostic methods, treatment strategy, and outcomes of patients diagnosed with rectus sheath hematoma. METHODS: Patients diagnosed and treated for spontaneous rectus sheath hematoma between January 2014 and December 2019 were included in the study. RESULTS: A total of 11 patients were diagnosed as spontaneous rectus sheath hematoma, with a median age of 63.5 ± IQR (55.5-73.25). 8 patients were treated by transfusion and medical therapy, while two patients underwent surgery and drainage. One patient was treated with arterial embolization. No mortality was encountered. CONCLUSION: Anticoagulant therapy was a major risk factor. Treatment is mostly based on supportive care to maintain hemodynamic stability. KEY WORDS: Abdominal pain, Hematoma, Interventional radiology, Rectus sheath.

Fabrication and Molecular Modeling of Navette-Shaped Fullerene Nanorods Using Tobacco Mosaic Virus as a Nanotemplate.

To date, metallization studies have been performed with the nanometer-scale template, Tobacco Mosaic Virus (TMV). Here we show that fullerenes as well can be deposited on TMV coat protein in a controlled manner. Two methods were followed for the coating process. First, underivatized fullerene was dispersed in different solvents to bring the underivatized fullerene and wild-type TMV together. Improved depositions were obtained with the fullerene dicarboxylic derivative synthesized via the Bingel method. The form of the coating was analyzed by transmission electron microscopy. Our results demonstrate that the coating efficiency with the carboxy derivative was much better compared to the underivatized fullerene. The goal of coupling a carbon nanoparticle to a biological molecule, the viral coat of TMV, was achieved with the carboxy derivative of fullerene, resulting in the production of navette-shaped nanorods. The interactions between carboxyfullerenes and TMV were investigated through modeling with computational simulations and Gaussian-based density functional theory (DFT) calculations using the Gaussian09 program package. The theoretical calculations supported the experimental findings. This inexpensive and untroublesome method promises new fullerene hybrid nanomaterials in particular shapes and structures.

A Fast and Reliable Method to Interpret Short-Term Mortality in Perforated Peptic Ulcer: Red Cell Distribution Width is Sensitive and Specific.

INTRODUCTION: Peptic ulcer is an important health problem worldwide with a prevalence of around 5%. Peptic ulcer perforation is a potentially mortal complication of peptic ulcer disease. We aimed to investigate the potential use of red cell distribution width as a prognostic marker in peptic ulcer perforation. METHODS: The files, operation notes, biochemical and hematological parameters, and prognosis of patients who were operated for a peptic ulcer perforation were reviewed in a retrospective cohort study. The relation of red cell distribution width (RDW) to main outcome in-hospital mortality was assessed. RESULTS: The mean age of the 172 patients was 40 ± 17.89. There were 158 (92%) males and 14 (8%) females. The in-hospital mortality was 8.7% (15/172). The median RDW in the group with mortality was 15.00 (interquartile range (IQR): 14.30-17.20) compared with the median RDW in the group with no mortality as 13.2 (IQR: 12.80-14.00, p ≤ 0.001). Receiver operator characteristic curves were plotted for RDW to identify nonsurvivors and yielded a significant area under the curve as 0.812 (95% confidence interval: 0.682-0.942). The sensitivity and specificity of RDW at a cutoff value of 14.25% were calculated with an accuracy of 81.98 (95% confidence interval: 75.40-87.41) as 80.00 (51.91-95.67) and 82.17 (75.27-87.81), respectively. CONCLUSION: Increased RDW may be of use to interpret mortality in patients with peptic ulcer perforation.

Biomimetic 3D-Bone Tissue Model.

Various approaches have been evaluated for developing three-dimensional (3D) scaffolds for modeling or engineering of the bone tissue. However, most of such attempts have come up short in mimicking the natural bone tissue extracellular matrix (ECM) microenvironment, especially its natural bioactive content. Here we describe the methodology for the preparation of a natural ECM-based multichannel construct as a biomimetic 3D bone tissue model. We elucidate the construction of the composite scaffold incorporating decellularized small intestinal submucosa ECM, synthetic hydroxyapatite and poly(ε-caprolactone), and the mechanical stimulation of the cell-seeded construct under bioreactor culture.

The Effects of Intervening With Synonasal Changes on Headaches in Migraine Patients Using Endonasal Surgery.

OBJECTIVE: Some anatomical changes might trigger headaches in people who have migraine, and that surgical applications eliminating the structural problems in treatment-resistant migraine patients are effective in pain treatment. METHODS: A total of 36 patients, who did not respond to different treatment options without aura migraine and chronic migraine that were showing synonasal and anatomical changes in synonasal nasal endoscopy and/or paranasal sinus CT screening, responding insufficiently and/or approximately one year period also did not respond to different treatment options, were included in this study between June 2016 and September 2019. RESULTS: The relation between migraine episodes and synonasal symptoms was found to be statistically significant. A significant difference was detected between nasal congestion and obstruction, postnasal discharge, and runny nose in patients with attacks compared to patients without attacks. The difference between mean pain severity values was statistically significant when compared to preoperative values (3.0(3.0∼4.0)) and post-operative values (1.0(0∼1.0)). When the pain severity after the operation (1.0(1.0∼2.75)) was compared with the severity of pain before the operation (5.0 (3.0∼5.0)), it was determined that there was a significant decrease in pain severity in patients diagnosed with chronic migraine, the difference between the mean pain severity values was statistically significant, and the prevalence of pain decreased at a significant level after the operation. CONCLUSION: The results of the present study indicate that the elimination of synonasal structural changes, which were hypothesized to trigger pain in migraine patients, could have a pain-reducing effect on the frequency and severity of the pain.

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective. Graphical Abstract.

Functions of Mesenchymal Stem Cells in Cardiac Repair.

Myocardial infarction (MI) and heart failure (HF) are significant contributors of mortality worldwide. Mesenchymal stem cells (MSCs) hold a great potential for cardiac regenerative medicine-based therapies. Their therapeutic potential has been widely investigated in various in-vitro and in-vivo preclinical models. Besides, they have been tested in clinical trials of MI and HF with various outcomes. Differentiation to lineages of cardiac cells, neovascularization, anti-fibrotic, anti-inflammatory, anti-apoptotic and immune modulatory effects are the main drivers of MSC functions during cardiac repair. However, the main mechanisms regulating these functions and cross-talk between cells are not fully known yet. Increasing line of evidence also suggests that secretomes of MSCs and/or their extracellular vesicles play significant roles in a paracrine manner while mediating these functions. This chapter aims to summarize and highlight cardiac repair functions of MSCs during cardiac repair.

Magnetic and electrically conductive silica-coated iron oxide/polyaniline nanocomposites for biomedical applications.

This work describes the development of novel dual-stimuli-responsive nanocomposites based on silica-coated iron oxide/polyaniline (Si-MNPs/PANI) for biomedical applications. Si-MNPs/PANI nanocomposites were developed via chemical oxidative polymerization of aniline in the presence of Si-MNPs (25 and 50 wt%). Si-MNPs/PANI were obtained both in nanotubular (SPNTs) and granular (SGTs) forms by altering the synthesis parameters such as acid concentration and mixing process. The effects of nanocomposite morphology were evaluated by investigating their chemical, physical and biological properties. Material characterization was comparatively carried out via SEM, TEM, FTIR, XRD, TGA, room temperature VSM, and electrical resistivity measurements. Biological properties were evaluated by indirect in vitro cytotoxicity and in vitro hemocompatibility analyses according to ISO standards. Results indicated that Si-MNPs/PANI nanocomposites exhibited both magnetically and electrically-responsive properties. Magnetization values of Si-MNPs/PANI nanocomposites increased with increasing Si-MNPs content. However, electrical conductivity was inversely proportional to Si-MNPs content. In addition, SGTs represented remarkably higher electrical conductivity (1.1 S/cm) than SPNTs (4.8 × 10-2 S/cm), but lower saturation magnetization (21 emu/g) compared to SPNTs (27 emu/g). Furthermore, in vitro cytocompatibility and hemocompatibility of the SGTs and SPNTs varied in a dose-dependent manner, suggesting their use in certain doses for biomedical applications. In conclusion, the developed Si-MNPs/PANI, with magnetic sensitivity and electrical conductivity have potential as nanocomposites for utilization in biomedical applications, e.g. biosensing, controlled-drug delivery, bioelectronic systems, tissue engineering and regenerative medicine as active compound. Besides, the selection of the appropriate synthesis protocol allows Si-MNPs/PANI nanocomposites to exhibit superior properties according to the targeted application area.

Mesenchymal Stem Cells for Coronavirus (COVID-19)-Induced Pneumonia: Revisiting the Paracrine Hypothesis with New Hopes?

Mesenchymal stem cells (MSCs) bear a promising potential for regenerative medicine therapies and they repair damaged tissue through secretion of immune modulatory and anti-inflammatory molecules acting in a paracrine fashion. Coronavirus disease 2019 (COVID-19) has spread all over the world with high morbidity and mortality rates and there is no specific treatment for this infection. A recent study published in the journal reports that MSC infusion is safe and effective in patients suffering from COVID-19 induced pneumonia. In the light of this study and previous reports, we make additional comments about possible therapeutic effects of MSCs in COVID-19 infection.

Evaluation of the stability of standard reference genes of adipose-derived mesenchymal stem cells during in vitro proliferation and differentiation.

Mesenchymal stem cells (MSCs) from a variety of sources are being used in pre-clinical and clinical studies. The choice of optimal source for treatment of diseases requires quantitative evaluation of self-renewal, proliferation and differentiation potencies of MSCs. For this purpose, quantitative real-time polymerase chain reaction (qRT-PCR) technique is used to determine the expression of genes. qRT-PCR requires the normalization of the gene expression levels by the use of reference genes in order to obtain accurate and reliable results. There is a limited number of studies focused on the selection of reference genes that are appropriate and reliable for MSCs. Thus, no single reference gene has yet been found for use in the in vitro proliferation and differentiation of MSCs. The aim of this study is to investigate the stability of the expression of widely used reference genes during the in vitro proliferation and differentiation of human adipose-derived mesenchymal stem cells (hASCs). For this purpose, 13 reference genes commonly used in MSC studies were selected. As a result, the expression stabilities of EF1α, RPLP0 and RPL13A genes were found to be high and were predicted to be suitable for use as reference genes for normalization in hASC studies. The GAPDH was identified as the gene with the lowest expression stability and evaluated to be an unsuitable reference gene for hASC differentiation studies. This piece of information could be crucial for the selection of appropriate reference genes and accurate measurement of gene expression in hASC studies.

Mesenchymal stem cell transplantation in polytrauma: Evaluation of bone and liver healing response in an experimental rat model.

PURPOSE: Trauma is the most common cause of death of young people in the world. As known, mesenchymal stem cells (MSCs) accelerate tissue regeneration mechanisms. In our study, we aimed to investigate the effects of MSCs transplantation on the healing of liver and bone tissue by considering trauma secondary inflammatory responses. METHODS: 56 adult Wistar-albino rats were divided into two groups: the polytrauma (liver and bone) (n = 28), and the liver trauma group (n = 28). At 36 h and 5th day after surgery, both rats with polytrauma and with isolated liver injury received either intravenous (IV) or intraperitoneal (IP) injections of MSCs (one million cells per kg body weight). Untreated groups received IV and IP saline injections. At day 21 after surgery, liver, tibia and fibula of the subjects were excised and evaluated for histopathologic and histomorphometric examination. Additionally, whole blood count (white blood cells, hemoglobin and platelets), C-reactive protein (CRP), glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, blood gas, and trauma markers interleukin-1B (IL-1B), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) levels were investigated. RESULTS: In general, MSC transplantations were well tolerated by the subjects. It was found that ALT, CRP, albumin were significantly lower in rats which received MSCs (p < 0.001). Inflammation of the liver and bone tissue in the MSC-injected rats were significantly lower than that of the untreated groups. CONCLUSIONS: Herewith we have shown that MSC infusion in posttraumatic rats leads to less aggressive and more effective consequences on liver and bone tissue healing. Human MSC treatment for trauma is still in early stages of development; thus standard protocols, and patient inclusion criteria should be established beforehand clinical trials.

Autologous protein-based scaffold composed of platelet lysate and aminated hyaluronic acid.

This study describes a protein-based scaffold using platelet rich plasma (PRP), aminated hyaluronic acid (HA-NH2) and Genipin for potential use in regenerative applications as an autologous tissue engineering scaffold. Human PRP was subjected to three freeze-thaw cycles for obtaining platelet lysates (PL). HA-NH2 was synthesized from hyaluronic acid. PL/HA-NH2 scaffolds were fabricated using different concentrations of genipin (0.05, 0.1 and 0.2%) and HA-NH2 (10, 20 and 30 mg/mL). Mechanical, physical, and chemical properties of the scaffolds were comprehensively investigated. The compressive test findings revealed that crosslinking with 0.1 and 0.2% genipin improved the mechanical properties of the scaffolds. SEM evaluations showed that the scaffolds exhibited an interconnected and macroporous structure. Besides, porosimetry analysis indicated a wide distribution of the scaffold pore-size. Rheological findings demonstrated that the G' values were higher than the G″ values, indicating that PL/HA-NH2 scaffolds had typical viscoelastic properties. In vitro biocompatibility studies showed that the scaffolds were both cytocompatible and hemocompatible. Alamar Blue test indicated that human adipose mesenchymal stem cells (hASCs) were able to attach, spread and proliferate on the scaffolds for 21 days-duration. Our findings clearly indicate that PL/HA-NH2 can be a promising autologous candidate scaffold for tissue engineering applications.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.

Decellularized bovine small intestinal submucosa-PCL/hydroxyapatite-based multilayer composite scaffold for hard tissue repair.

This study involved the development of a multilayer osteogenic tissue scaffold by assembling decellularized bovine small intestinal submucosa (bSIS) layers, together with synthetic hydroxyapatite microparticles (HAp) and poly(ε-caprolactone) (PCL) as the binder. As a first step, the surface and mechanical properties of the developed scaffold was determined, after which the biocompatibility was evaluated through seeding with isolated rat bone marrow mesenchymal stem cells (BM-MSCs). Then, a 21-day culture study was performed to investigate the in vitro osteoinductive potential of the scaffold on BM-MSCs under standard and osteogenic culture conditions. The SEM findings indicated that a uniform multilayer and perforated structure was acquired; that the HAp microparticles were homogenously distributed within the structure; and that the PCL-bound laminar scaffold had structural integrity. Mechanical tests revealed that the scaffold maintained its mechanical stability for at least 21 days in culture, with no changes in the first-day maximum strength and maximum stress values of 625.123 ±â€¯70.531 N and 6.57762 ±â€¯0.742 MPa, respectively. MTT and SEM analyses together revealed that BM-MSCs preserved their viability and proliferated during a 14-day culture period on the multilayer scaffold. Immunofluorescence analyses indicated that cells on the scaffold differentiated into the osteogenic lineage, by the culture-time-dependent increase in osteogenic markers' expression, i.e. Alkaline phosphatase, Osteopontin, and Osteocalcin. It was also clear that, the osteoinductive effect by the composite scaffold on BM-MSCs could be achieved even without the use of any external osteogenic inducers.

Encapsulation of bone marrow-MSCs in PRP-derived fibrin microbeads and preliminary evaluation in a volumetric muscle loss injury rat model: modular muscle tissue engineering.

Repair of volumetric muscle loss (VML) injuries is a complicated endeavour which necessitates the collaborative use of different regenerative approaches and technologies. Herein is proposed the development of fibrin-based microbeads (FMs) alone or as a bone marrow mesenchymal stem cell (MSC) encapsulation matrix for modular muscle engineering. FMs were generated through the ionotropic gelation of alginate and fibrinogen obtained from the platelet-rich plasma of whole blood, and then removing the alginate by citrate treatment. FMs were first characterized by FT-IR, SEM and water uptake tests. Then, the stability of FMs and the mitochondrial dehydrogenase activity of the MSCs encapsulated in FMs were evaluated under in vitro culture conditions. Eventually, the regenerative capacity of the cell-devoid and MSCs-encapsulated FMs was evaluated in a rat VML injury model involving 8 × 4×4 mm3-size bilateral defects in the biceps femoris muscles. The histochemical, immunohistochemical and semi-quantitative histomorphological scoring results retrieved at 30, 60 and 180 days demonstrated that the cell-devoid FMs supported muscle regeneration to a great extent. Moreover, MSCs-encapsulated FMs were more effective in shortening the regeneration period of the injured tissue of the rat VML, resulting in good myofibre orientation, while the Sham group resulted in incomplete repair with fibrotic scar tissue formations.

Decellularized bSIS-ECM as a Regenerative Biomaterial for Skin Wound Repair.

Tissue engineering-based regenerative applications can involve the use of stem cells for the treatment of non-healing wounds. Multipotent mesenchymal stem cells have become a focus of skin injury treatments along with many other injury types owing to their unprecedented advantages. However, there are certain limitations concerning the solo use of stem cells in skin wound repair. Natural bioactive extracellular matrix-based scaffolds have great potential for overcoming these limitations by supporting the regenerative activity and localization of stem cells. This chapter describes the use of bone marrow mesenchymal stem cells together with decellularized bovine small intestinal submucosa (SIS), for the treatment of a critical-sized full-thickness skin defect in a small animal model.