The effect of acellular scaffold loaded with Wharton's jelly-derived stem cells and mineral pitch on healing of burn model in rat.

Severe burns often result in an exacerbated inflammatory response, which can contribute to further injury. This inflammatory response may lead to an increased risk of infection, multiple organ failure, and death. This study aimed to investigate the potential of reducing inflammation to enhance burn wound healing in rats using ovine's small intestinal submucosa as a carrier for Wharton's jelly mesenchymal stem cells (WJ-MSCs) and Mineral Pitch (MP). A rat burn model was developed, and the animals were divided into four groups: control group: burn, placebo group: scaffold-treated burn, cell experimental group: WJ-MSCs seeded scaffold-treated burn, and cell and MP experimental group: scaffolds loaded with WJ-MSCs and MP-treated burn. After treating the wounds in the relevant groups and sampling them on days 5, 14 and 21, histological and pathological parameters, and the expression of genes involved in angiogenesis and epithelialization were evaluated. The study results revealed several findings in the burn wounds. These included changes in mast cell populations, a decrease in inflammatory neutrophils and lymphocytes, an increase in fibroblasts and blood vessels, and upregulation of angiogenesis and epithelialization genes. These changes collectively contributed to enhanced wound healing in cell and MP experimental group compared to the other groups. The findings suggest that scaffolds loaded with Wharton's jelly-derived stem cells and MP can serve as engineered tools to modulate inflammatory conditions during the burn wound healing process. These interventions can improve burn wound management and promote better outcomes.

Evaluation the ability of acellular ovine small intestine submucosa to load and release of mineral pitch and its anti-inflammatory effects.

Injury from the severe burn is exacerbated by a persistent inflammatory response. This response is mediated by cytokines and chemokines, which are released from various immune cells, including mast cells. In this study, the ability of the acellular ovine small intestine submucosa (AOSIS) to load and release of Mineral Pitch (MP) was first investigated, and it was found that the preparation of the scaffold by a modified method enables it to load and release water-soluble drugs. Then, 32 male Wistar rats were divided into four groups, a third-degree burn was created, and except for the control group, the others were treated with: AOSIS, WJ-MSCs seeded AOSIS, or AOSIS loaded with WJ-MSCs and MP. Wound sampling on the 5th day after treatment showed that the number of intact and degranulated mast cells in the treatment groups was associated with a decrease compared to the control group. In the last group, this decrease was the largest (and statically significant (p < 0.05)). Also, by measuring the level of inflammatory factors in blood serum, it was found that in the treatment groups compared to the control group, IL-10 was associated with an increase, and TNF-α was associated with a decrease. The changes in inflammatory factors were more significant (p < 0.05) in the last group. So, our results indicate that AOSIS loaded with WJ-MSCs and MP could be used as an innovative tissue-engineered device to control inflammatory condition during burn wound healing.

Melatonin and its mechanism of action in the female reproductive system and related malignancies.

Melatonin (N-acetyl-5-methoxytryptamine), the main product of pineal gland in vertebrates, is well known for its multifunctional role which has great influences on the reproductive system. Recent studies documented that melatonin is a powerful free radical scavenger that affects the reproductive system function and female infertility by MT1 and MT2 receptors. Furthermore, cancer researches indicate the influence of melatonin on the modulation of tumor cell signaling pathways resulting in growth inhibitor of the both in vivo/in vitro models. Cancer adjuvant therapy can also benefit from melatonin through therapeutic impact and decreasing the side effects of radiation and chemotherapy. This article reviews the scientific evidence about the influence of melatonin and its mechanism of action on the fertility potential, physiological alteration, and anticancer efficacy, during experimental and clinical studies.

Using 3D-bioprinting scaffold loaded with adipose-derived stem cells to burns wound healing.

Three dimensional (3D) printing has recently expanded in popularity and has become an effective approach for tissue engineering. Advances in tissue engineering have increased the effectiveness of cell-based therapies. Indeed, the ultimate goal of such treatment is the development of conditions similar to fetal wound regeneration. In this context, technology of 3D printing also allows researchers to more effectively compose multi-material and cell-laden scaffolds with less effort. In this study, we explored a synthetic gel scaffold derived from 3D bioprinter with or without stem cells to accelerate wound healing and skin defects. Adipose-derived stem cells (ADSCs) were isolated and seeded into 3D bioprinter derived-gel scaffold. Morphological and cell adherence properties of 3D scaffold were assessed by hemotoxylin & eosin (H&E) staining and scanning electron microscopy and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide assay. In vivo assessment of the scaffold was done using H&E staining in the full-thickness burn rat model. The experimental groups included; (a) untreated (control), (b) 3D bioprinter derived-gel scaffold (Trial 1), and (c) 3D bioprinter derived-gel scaffold loaded with ADSC (Trial 2). Our results represented 3D bioprinter derived-gel scaffold with or without ADSCs accelerated wound contraction and healing compared to control groups. Epithelization was completed until 21 days after operation in scaffold alone. In scaffold with ADSCs group, epithelization was faster and formed a multi-layered epidermis with the onset of cornification. In conclusion, 3D bioprinter derived-gel scaffold with or without ADSCs has the potential to be used as a wound graft material in skin regenerative medicine.

The useful agent to have an ideal biological scaffold.

Tissue engineering which is applied in regenerative medicine has three basic components: cells, scaffolds and growth factors. This multidisciplinary field can regulate cell behaviors in different conditions using scaffolds and growth factors. Scaffolds perform this regulation with their structural, mechanical, functional and bioinductive properties and growth factors by attaching to and activating their receptors in cells. There are various types of biological extracellular matrix (ECM) and polymeric scaffolds in tissue engineering. Recently, many researchers have turned to using biological ECM rather than polymeric scaffolds because of its safety and growth factors. Therefore, selection the right scaffold with the best properties tailored to clinical use is an ideal way to regulate cell behaviors in order to repair or improve damaged tissue functions in regenerative medicine. In this review we first divided properties of biological scaffold into intrinsic and extrinsic elements and then explain the components of each element. Finally, the types of scaffold storage methods and their advantages and disadvantages are examined.

Effect of Mineral Pitch on the Proliferation of Human Adipose Derived Stem Cells on Acellular Scaffold.

Purpose: Acellular scaffold extracted from extracellular matrix (ECM) have been used for constructive and regenerative medicine. Adipose derived stem cells (ADSCs) can enhance the vascularization capacity of scaffolds. High mobility group box 1 (HMGB1) and stromal derived factor1 (SDF1) are considered as two important factors in vascularization and immunologic system. In this study, the effect of mineral pitch on the proliferation of human ADSCs was evaluated. In addition to HMGB1 and SDF1, factors expression in acellular scaffold was also assessed. Methods: To determine acellular scaffold morphology and the degree of decellularization, hematoxylin & eosin (H&E), 6-diamidino-2-phenylindole (DAPI), and Masson's trichrome staining were applied. The scaffolds were treated with mineral pitch. Also, ADSCs were seeded on the scaffolds, and adhesion of the cells to the scaffolds were assessed using field emission scanning electron microscopy (FE-SEM). In addition, the efficiency of mineral pitch to induce the proliferation of ADSCs on the scaffolds was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. To measure HMGB1 and SDF1 mRNA expression, real-time polymerase chain reactions (RT-PCR) was used. Results: FE-SEM showed that decellularized matrix possesses similar matrix morphology with a randomly oriented fibrillar structure and interconnecting pores. No toxicity was observed in all treatments, and cell proliferation were supported in scaffolds. The important point is that, the proliferation capacity of ADSCs on Mineral pitch loaded scaffolds significantly increased after 48 h incubation time compared to the unloaded scaffold (P<0.001). Conclusion: The results of this study suggest that mineral pitch has potentials to accelerate proliferation of ADSCs on the acellular scaffolds.

Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors.

Fibroblast plays a key role in wound healing, and the advantages of mesenchymal stem cells (MSC) secretome in wound healing have previously been reported. In the present study, we investigated the impact of human bone marrow MSC-conditioned media (CM) on skin wound healing in diabetic rats and found that some improvements occurred mainly through fibroblast functions. Then, we scrutinized the impact of MSC-CM treatment on fibroblast cellular behavior by culturing human dermal fibroblasts (HDFs) in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in some healing kinetics of diabetic wound which received MSC-CM. Particularly, MSC-CM-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wound had less pronounced inflammatory response, better tissue remodeling, and more vascularization compared with non-treated diabetic ones. Gene expression analyses indicated that MSC-CM treatment leads to upregulation of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) genes. In addition, a significantly higher cell viability/proliferation, migration, and bFGF gene expression were observed when MSC-CM was used to treat HDFs in HG culture media. Based on these findings, it is suggested that MSC-CM could promote wound repair and skin regeneration, in some major processes, via improvement of cellular behaviors of fibroblasts in the diabetic microenvironment. The beneficial advantages of mesenchymal stem cells-conditioned media on fibroblast cellular behaviors and wound healing may lead to establish a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions.

Skin Burns: Review of Molecular Mechanisms and Therapeutic Approaches.

Burn wounds are one of the main causes of skin damage. Based on World Health Organization statistics, almost 300 000 people worldwide die of burns each year. In severe burns, the cells and blood vessels are often injured and the blood supply to the wound is disturbed. Many factors such as oxygenation, infection, aging, hormones, and nutrition potentially can influence burn progression and disrupt repair with unbalanced release of various growth factors and cytokines. Different treatment approaches such as dressings and skin substitutes have been applied to aid wound healing. A thorough understanding of the effective factors on burns can improve wound healing outcomes. This review evaluates articles published on the Scopus, EMBASE, and PubMed databases that attempt to explain the pathophysiology, molecular components, and therapeutic approaches involved in the burn wound healing process.