Design and characterization of electroactive gelatin methacrylate hydrogel incorporated with gold nanoparticles empowered with parahydroxybenzaldehyde and curcumin for advanced tissue engineering applications.

Electroconductive polymers are the materials of interest for the fabrication of electro-conductive tissues. Metal ions through the redox systems offer polymers with electrical conductivity. In this study, we processed a gelatin methacrylate (GelMA) network with gold nanoparticles (GNPs) through a redox system with parahydroxybenzaldehyde (PHB) or curcumin to enhance its electrical conductivity. Induction of the redox system with both PHB and curcumin into the GelMA, introduced some new functional groups into the polymeric network, as it has been confirmed by H-NMR and FTIR. These new bonds resulted in higher electro-conductivity when GNPs were added to the polymer. Higher electroactivity was achieved by PHB compared to the curcumin-induced redox system, and the addition of GNPs without redox system induction showed the lowest electroactivity. MTT was used to evaluate the biocompatibility of the resultant polymers, and the PHB-treated hydrogels showed higher proliferative effects on the cells. The findings of this study suggest that the introduction of a redox system by PHB in the GelMA network along with GNPs can contribute to the electrochemical properties of the material. This electroactivity can be advantageous for tissue engineering of electro-conductive tissues like cardiac and nervous tissues.

Statistical study of clinical trials with stem cells and their function in skin wound.

Mesenchymal stem cells (MSCs) have been known as a reliable and effective source to repair damaged tissues. The differentiation and self-renewal ability, easy access, immune system modulation capability, and important role in the process of repairing wounds have caused using these cells extensively in wound healing. In this review study, the role of MSCs is debated about different diseases especially in repairing skin wounds. This review article was obtained from 75 basic and trial articles on the PubMed, Google Scholar, and Clinical Trials databases between 2000 and 2022. MSCs are capable of migrating to the wound site and are effective in all stages of wound healing. These cells differentiate into skin cells and also inhibit inflammatory responses, proliferation, and differentiation cells through paracrine messages. They stimulate locally resident precursors, leading to angiogenesis, epithelial regeneration, and granular tissue formation. During maturation stages, these cells decrease fibrosis tissue formation and wound contraction and increase collagen expression and wound tensile strength. The molecular factors of the lesion site change function of these cells and cause MSCs to create a wound healing microenvironment instead of a fibrotic microenvironment. Currently, significant advances have been achieved in the delivery of MSCs to wound sites. These cells are injected intravenously or intradermally, with or without a scaffold. They are also used in the form of spray or hydrogels. Furthermore, the extracellular vesicles and the synergistic environment of these cells alone are effective. Forthcoming studies could lead to more effective treatment strategies for the use of MSCs in wound healing.

Adipose tissue-derived stem cells upon decellularized ovine small intestine submucosa for tissue regeneration: An optimization and comparison method.

The extracellular matrix of different mammalian tissues is commonly used as scaffolds in the field of tissue engineering. One of these tissues, which has frequently been studied due to its structural and biological features, is the small intestine submucosal membrane. These research are mainly done on the porcine small intestine. However, a report has recently been published about a scaffold produced from the submucosal layer of the ovine small intestine. In the present study, ovine small intestine submucosal (OSIS) was decellularized in a modified manner and its histological, morphological, and biomechanical properties were studied. Decellularization was performed in two phases: physical and chemical. In this method, a chloroform-methanol mixture, enzymatic digestion, and a constant dose of sodium dodecyl sulfate (SDS) was used in the least agitation time and its histological property and biocompatibility were evaluated in the presence of adipose tissue-derived stem cells (ADSCs); furthermore, ADSCs were isolated with a simple method (modified physical washing non-enzymatic isolation). The results were showed that the use of OSIS could be effective and operative. Mechanical properties, histological structure and shape, and glycosaminoglycan content were preserved. In the SDS-treated group, more than 90% of the native cells of tissue were deleted, and also in this group, no toxicity was observed and cell proliferation was supported, compared to the untreated group. Therefore, our results indicate that ADSCs seeded on OSIS scaffold could be used as a new approach in regenerative medicine as hybrid or hydrogel application.

A silk fibroin/decellularized extract of Wharton's jelly hydrogel intended for cartilage tissue engineering.

A hybrid hydrogel was obtained from decellularized extract from Wharton's jelly (DEWJ) and silk fibroin (SF) and characterized for cartilage tissue engineering. Wharton's jelly was used due to its similarity with articular cartilage in extracellular matrix composition. Also, silk fibroin has good mechanical properties which make this construct appropriate for cartilage repair. Decellularization of Wharton's jelly was verified by DAPI staining, DNA quantification, and PCR analysis. Then, the biochemical composition of DEWJ was determined by ELISA kits for total proteins, collagens, sulfated glycosaminoglycans (sGAG), and transforming growth factor ß1 (TGF-ß1). After fabricating pure SF and SF/DEWJ hybrid hydrogels, their physical and mechanical properties were characterized by FESEM, Fourier-transform infrared spectroscopy (FTIR) and rheological assays (amplitude and frequency sweeps). Furthermore, cell viability and proliferation were assessed by MTT assay. The results have shown that DEWJ in hybrid hydrogels enhances mechanical properties of the construct relative to pure SF hydrogels. Also, this extract at its 40% concentration in culture media and 20% or 40% concentrations in SF/DEWJ hybrid hydrogels significantly increases population of the cells compared to control and pure SF hydrogel after 7 days. In conclusion, this study proposes the potential of SF/DEWJ hybrid hydrogels for cartilage tissue engineering applications.

Polyurethane-Polycaprolactone Blend Patches: Scaffold Characterization and Cardiomyoblast Adhesion, Proliferation, and Function.

A remarkable challenge in myocardial tissue engineering is the development of biomimetic constructs that can potentially improve myocardial repair and regeneration. Polyurethane (PU) scaffolds are extensively utilized in the cardiovascular system. We have synthesized a new biodegradable poly(ester-ether urethane urea) (PEEUU) using a new and simple method. To enhance mechanical and physicochemical properties, the PEEUU was blended with polycaprolactone (PCL). We then fabricated a series of new PU-PCL scaffolds. The scaffolds were then characterized using SEM, porosity measurement, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), DSC, water contact angle measurement, swelling measurement, in vitro degradation rate, and mechanical tests. Expression of the cardiac-specific proteins on the scaffolds was investigated using immunofluorescence staining and quantitative real-time PCR. The elasticity of blends increased with an increase of PEEUU. In the blend scaffolds, the size and interconnectivity of pores were in an appropriate range (142-170 µm) as reported in the literature. These blend scaffolds revealed high cell metabolic activity for cardiomyoblasts and also enabled cells to proliferate and express cardiac marker proteins at higher rates. Histological examination of subcutaneously transplanted scaffolds after two months revealed degradation in the blend scaffolds. It is demonstrated that functionality of cells is sensitive to the composition of biomaterials used, and the effective cell-biomaterial interactions are critical in order to create a functional tissue engineered product that allows seeded cells to develop their normal activity. The PEEUU-PCL blends could potentially provide a versatile platform to fabricate functional scaffolds with an effective cell-biomaterial interaction for cardiac tissue regeneration.

Characterization of decellularized ovine small intestine submucosal layer as extracellular matrix-based scaffold for tissue engineering.

Extracellular matrix-based scaffolds derived from mammalian tissues have been used in tissue engineering applications. Among all the tissues, decellularized small intestine submucosal layer (SIS) has been recently investigated for its exceptional characteristics and biocompatibilities. These investigations have been mainly focused on the decellularized porcine SIS; however, there has not been any report on ovine SIS (OSIS) layer. In this study, OSIS was decellularized and its physical, chemical, and morphological properties were evaluated. Decellularization was carried out using chemical reagents and various physical conditions. The effects of different conditions were evaluated on histological and biomechanical properties, quality of residual DNA, GAPDH gene expression, and biocompatibility. Results revealed satisfactory decellularization of OSIS which could be due to its thin thickness. Mechanical properties, structural form, and glycosaminoglycan contents were preserved in all the decellularized groups. In SDS-treated groups, further cells and DNA residues were removed compared to the groups treated with Triton X-100 only. No toxicity was observed in all treatments, and viability, expansion, and cell proliferation were supported. In conclusion, our results suggest that OSIS decellularized scaffold could be considered as an appropriate biological scaffold for tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 933-944, 2018.

Critical-sized full-thickness skin defect regeneration using ovine small intestinal submucosa with or without mesenchymal stem cells in rat model.

Decellularized extracellular matrices (ECM) based materials are routinely used for a variety of clinical applications. Hereof, in vivo application of decellularized ovine small intestinal submucosal (DOSIS) layer as, a scaffold is yet to be investigated. In this study, the effectiveness of the DOSIS scaffold, with or without rat bone marrow mesenchymal stem cells (BM-MSCs), in full-thickness wound healing of critical-sized defect was experimentally studied in a rat model. The experimental groups included; group I (control), group II (DOSIS), and group III (BM-MSCs-seeded DOSIS). Wound healing of all groups was examined and compared clinically and histopathologically on days 7, 14, and 21 postoperation. Our results represented BM-MSCs-seeded DOSIS accelerated wound contraction and healing compared to both the DOSIS alone and control groups. Epithelization was close to completion 21 days postoperation in DOSIS alone. In OSIS with BM-MSCs group, epithelization was faster and had fully taken place at the subsequent time points. DOSIS layer, as cell-free form with low substantially DNA content, accelerated healing of rat skin wound defects that was created at critical-size and full-thickness. In conclusion, decellularized OSIS alone and in combination with BM-MSCs has the potential to be used as a wound graft material in skin regenerative medicine. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2177-2190, 2018.

Protective Role of GnRH Antagonist on Chemotherapy-induced Spermatogenesis Disorder: A Morphological Study.

PURPOSE: Anti cancer drugs is one of the most important chemotherapeutic factors which can influence spermatogenesis process and germinal epithelium. Since dividing cells are mainly affected by anticancer drugs, the aim of the present study is to investigate the preventive effect of GnRH antagonist on spermatogenic defect produced by anticancer drugs. METHODS: In the present study thirty adult male mice aging 6-8 weeks were divided into 3 groups as: Control, Experimental 1 and Experimental 2. Experimental 1 group received Cisplatin for 5 days as 2.5 mg/kg intraperitoneally and Experimental 2 group received 0.25 mg/kg cetrorelix (GnRH antagonist) one week before cisplatin treatment and continued for 3 weeks. The mice in all groups were sacrificed 35 days after the last injection and testis specimens were fixed in boueins, formaldehyde fixative and 2.5% Glutaraldehide then prepared for light and electron microscopic examination. RESULTS: Light microscopy (LM) study showed that the number of spermatogonial cells, thickness of germinal epithelium, was decreased in Experimental 1group. Electron microscopy revealed that in this group several intercellular spaces appeared between spermatogenic cells and secretory granules in interstitial cells was increased. There were several vacuolated mitochondria and destroyed organelles in spermatogonial cells but in Experimental 2 group condition was similar to control group. CONCLUSION: These results indicate that the cetrorelix administration before cancer treatment may protect germinal epithelium against side effects of cisplatin.

Degenerative effect of Cisplatin on testicular germinal epithelium.

PURPOSE: The present study was designed to explore the effect of intraperitoneal administration of cisplatin in germinal epithelium of mice. There are few reports on the side effect of cisplatin on spermatogenesis when are used as anticancer drug. Therefore, in the present study the effect of cisplatin on spermatogenesis was evaluated by electron microscopy. METHODS: Twenty balb/c mice aging 6-8 weeks was used in this study. The mice were divided into two groups, control and cysplatin treated. cysplatin was injected for five days as 2.5 mg /kg. The mice were sacrificed after 5 weeks and testicular specimens were removed, fixed in boueins, formaldeyd fixative and 2.5% Glutaraldehide then prepared for light and electron microscopic study. RESULTS: Observation with optic microscope in treated group thickness of germinal epithelium was reduced a lot and increased the number of apoptotic cells. In some seminiferous tubules only sertoli cells were observed and nucleus of spermatogony cells was hetrochromatin. The electron microscopic observations showed some irregularity waviness and thickening in basal layer. Also myoid cells of this group were thick and contracted. In this group many apoptotic cells and damaged organelles were seen. CONCLUSION: It was indicated that cisplatin affected testicular germinal epithelium by both cytotoxic effect and induction of apoptosis.