Ali Samadikuchaksaraei

Pressure ulcers remain challenging to treat because ischemia, extracellular matrix disruption, and impaired angiogenesis create a wound microenvironment that limits effective regeneration. Here, an injectable thermosensitive hydrogel has been developed based on human placenta‐derived soluble extracellular matrix (sECM) and low‐dose copper sulfate (CuSO ₄ ), combined with endothelial progenitor cells (EPCs), to address multiple aspects of this pathology. Hydrogels were formulated using methylcellulose and characterized for rheological properties, swelling, degradation, and microstructure. EPC phenotype, viability, and proliferative activity were assessed by flow cytometry, live/dead staining, and MTT assay. Therapeutic performance was evaluated in a magnet‐induced ischemic pressure ulcer model using macroscopic and histological analyses. Incorporation of sECM and CuSO ₄ modified gelation behavior, improved mechanical properties, and increased pore size. Low‐dose CuSO ₄ (0.1% w/v) supported EPC viability and proliferation, whereas higher concentrations were cytotoxic. In vivo, hydrogels containing EPCs markedly accelerated wound closure, reducing wound area to 32.72% ± 1.04% at day 7, 11.33% ± 1.46% at day 14, and 1.24% ± 0.66% at day 21, compared with 17.35% ± 0.68% residual wound area in controls at day 21. Histological analysis further demonstrated enhanced tissue regeneration, with increased hair follicle density (up to 10 ± 0.63 vs. 1 ± 0.6 in controls) and greater collagen deposition (up to 85.26% ± 0.75% vs. 74.32% ± 0.75% in controls). These findings indicate that a placental ECM–copper hydrogel incorporating EPCs provides a promising biomaterial approach for pressure ulcer repair by combining structural support with pro‐angiogenic and cellular contributions.

Acute lung injury (ALI) is a critical condition with limited treatment options. This study evaluates the therapeutic potential of human fetal lung-derived mesenchymal stem cells (hFL-MSCs) in an experimental model of ALI. Our proof-of-concept findings suggest a paradigm shift in the approach to cell sourcing for lung diseases, proposing that fetal lung cells may be potential targets for stem cell differentiation studies when the derived cells are intended to be used for lung cell therapy. After characterizing hFL-MSCs, 18-week fetal lung cells were intratracheally instilled into rats with bleomycin-induced ALI. All the animals were evaluated on days 3 − 28 post-injury for cell count and the cytokines in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, lung tissue histological staining and expression of an extracellular matrix component, inflammatory and fibrotic genes. The findings confirm mesenchymal stem cell identity of the isolated cells and stability in their cell cycle distribution. Analysis of BALF showed that immune cell response to acute inflammation and adaptive immunity was significantly ameliorated by cell therapy with hFL-MSCs. Same results were confirmed by the levels of IL-6, TNF-α, IL-10 and NO in BALF, the lung wet/dry weight ratio and histopathological analysis of lung tissues after H&E and Masson’s trichrome staining. Effective modulation of key pro-inflammatory (Il6, Tnf, Il1b), pro-fibrotic (Tgfb1) and Col1a1 genes were also confirmed after therapy with hFL-MSCs. Our findings suggest that fetal lung tissue-specific stem cells are viable options for lung cell therapy and could be considered as targets for engineering of regenerative cells for lung diseases.

Management of infected diabetic wounds with large amounts of biofluid is challenging to treat due to localized edema-induced ischemia. Traditional hydrophilic dressings retain wound exudate, raise bacterial infection, and hinder wound healing. Herein, a multifunctional double-layer Janus fibrous hydrogel with a hydrophobic and superhydrophilic potential was designed to accelerate the healing of infected diabetic wounds. The outer hydrophobic layer is composed of a poly(vinylidene fluoride)/cellulose acetate-based nanofibrous composite. In contrast, the inner superhydrophilic layer is composed of photo-cross-linked gelatin methacrylate/polycaprolactone based nanofibrous hydrogel coated with a zinc-dopamine-based metal-phenolic network complex. The bilayer Janus fibrous hydrogel was characterized for its structural, physicochemical, mechanical, swelling, antioxidant, antibacterial, and cytocompatibility properties. Results indicated that the outer hydrophobic layer possesses excellent antifouling self-cleaning potential and can prevent the entry of environmental microorganisms and moisture. On the other hand, the supramolecular complex coated inner layer possesses good antibacterial, antioxidant, and cell-supportive properties. Furthermore, the potential of Janus fibrous hydrogel for infected wound healing was evaluated by using infected diabetic BALB/c mice. The in vivo bacterial invasions and histological and immunological results indicated that the Janus fibrous hydrogel possesses good wound reconstruction potential, angiogenesis, and collagen deposition, making it appropriate for diabetic wound treatment.

Skin is the largest protective tissue of the body and is at risk of damage. Hence, the design and development of wound dressing materials is key for tissue repair and regeneration. Although silk fibroin is a known biopolymer in tissue engineering, its degradation rate is not correlated with wound closure rate. To address this disadvantage, we mimicked the hierarchical structure of skin and also provided antibacterial properties; a hydrogel with globular structure consisting of silk fibroin, pluronic F127, and curcumin was developed. In this regard, the effect of pluronic and curcumin on the structural and mechanical properties of the hydrogel was studied. The results showed that curcumin affected the particle size, crystallinity, and ultimate elongation of the hydrogels. In vitro assays confirmed that the hydrogel containing curcumin is not cytotoxic while the diffused curcumin and pluronic provided a considerable bactericidal property against Methicillin-resistant Staphylococcus aureus. Interestingly, presence of pluronic caused more than a 99% reduction in planktonic and adherent bacteria in the curcumin-free hydrogel groups. Moreover, curcumin improved this number further and inhibited bacteria adhesion to prevent biofilm formation. Overall, the developed hydrogel showed the potential to be used for skin tissue regeneration.

Injectable in situ‐forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt‐doped bioactive glass (BG)‐loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl₂. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast‐like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well‐dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear‐thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A‐S‐G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A‐S‐G5Co. Finally, the in vivo study demonstrated that A‐S‐G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow‐up. These results show that incorporation of SF/gelatin microspheres containing cobalt‐doped BG in an injectable in situ‐forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis.

The development of electrospun tissue engineering scaffolds using silk fibroin and polycaprolactone (PCL) has been reported. The challenge in this system is the design of a suitable solvent with high stability. In this study, a mat was electrospun with PCL‐fibroin fibers using an emulsion consisting of PCL and a blend of fibroin and polyethylene oxide (PEO). The effects of different concentrations of fibroin and PEO and ratios of formic acid: distilled water (FA:DW, solvent for fibroin and PEO) and chloroform: formic acid (Chl:FA, solvent for PCL) were studied. The FA:DW and Chl:FA ratios of 70:30 were proved to make an optimized and stable solvent system. In addition, by controlling the water absorption of the mat, we optimized its weight loss and maintained its integrity for up to 14 days. Also, the mechanical and cell attachment properties were as expected. Chorioallantoic membrane (CAM) assay exhibited the potential of the mats to induce angiogenesis. Furthermore, subcutaneous implantation in a mouse model elicited no significant inflammatory response. This study provides a simple and promising electrospinning fabrication with an optimized solvent system for tissue engineering applications.