Stem Cells and Hydrogels for Liver Tissue Engineering: Synergistic Cure for Liver Regeneration

The liver is one of the body's tissues that has regenerative abilities. But if the damage is too much, it needs to medical interventions for the regeneration. Liver donor shortage causes researchers to turn to other treatments. Tissue engineering is a new approach to liver regeneration. Hydrogels are polymeric networks of hydrophilic, flexible, and similar to natural tissue. Therefore, they are used to encapsulate cells These constructs are potent substrates to induce differentiation of stem cells to the hepatocytes. According to inadequate availability of the hepatocytes, an alternative cell is required to produce hepatocyte-like cells. Due to the self-renewal and differentiation properties of stem cells, they are suitable cell sources to replace the lostcells. This review has focused on liver regeneration, advantages and disadvantages of hydrogels for liver regeneration, injectable materials, hydrogel fabrication methods, including 3D printing, and stem cells for liver regeneration. Furthermore, this paper shows in vitro, preclinical, and clinical trial studies of hydrogel and stem cells for liver regeneration. Keywords:Liver regeneration; Stem cells; Hydrogel; Preclinical trial; Clinical tria

Resveratrol-loaded polyurethane nanofibrous scaffold: Viability of endothelial and smooth muscle cells

Acellular small-caliber tissue-engineered vascular grafts (SCTEVGs) have low patency rate due to complications including thrombosis and intimal hyperplasia. Rapid endothelialization, antithrombosis and antiproliferation approaches are suitable for dispelling these complications. Nevertheless, common antithrombosis and antiproliferation techniques are usually incompatible with rapid endothelialization on vascular grafts. To overcome these obstacles, we developed nanofibrous polyurethane scaffolds loaded with resveratrol drug, which is a natural compound extracted from plants and shows multifaceted effects in cardiovascular protection. It was found that the tensile strength and Young's modulus in modified scaffolds were significantly increased by resveratrol loading into membranes. The tensile strengths and breaking strains of resveratrol-loaded scaffolds were close to that of native vessels. The resveratrol release profile from the nanofibrous scaffolds occurred in a sustained manner. The anti-thrombogenicity of resveratrol-loaded nanofibers increased compared to polyurethane alone, with the result that prolonged human blood clotting time and lower hemolysis were detected on these scaffolds. The viability of human umbilical vein endothelial cells and smooth muscle cells on resveratrol-loaded scaffolds was evaluated. Our findings demonstrated that resveratrol-loaded nanofibers resulted in not only appropriate antithrombotic properties, but the formation of a monolayer of endothelial cells on the scaffold surface and lower smooth muscle cell growth. These resveratrol-loaded nanofibers are suggested as potential scaffolds for SCTEVGs

Influence of pore sizes in 3D-scaffolds on mechanical properties of scaffolds and survival, distribution, and proliferation of human chondrocytes

Articular cartilage has weak intrinsic self-healing capacity. Tissue engineering is an appropriate option for cartilage regeneration. This research was designed to evaluate the effects of pore size in scaffolds on mechanical properties and chondrocyte-scaffold interactions. PCL scaffolds were fabricated with large, medium, and small pore sizes. The constructs were analyzed by SEM, swelling tests, mechanical tests, MTT assay, and H&E staining after chondrocyte seeding. Mechanical features of the scaffolds were near to human articular cartilage. Our findings suggest that the PCL scaffold with medium pore sizes provides suitable mechanical strength and better chondrocyte-scaffold interactions simultaneously for application in cartilage

Natural biomacromolecule based composite scaffolds from silk fibroin, gelatin and chitosan toward tissue engineering applications

Natupolymer-based scaffolds can increase cell affinity to biomaterials and improve cell responses. Silk fibroin, chitosan and gelatin that mimic the properties of natural extra-cellular matrix (ECM) were chosen due to their biocompatibility, biodegradability and less immunogenic reactions. We prepared composite scaffolds with different blending ratios of silk fibroin-chitosan-gelatin by freeze-drying technique. Silk fibroin was extracted from the Bombyx mori silkworm. The scaffolds were characterized by scanning electron microscopy (SEM), surface wettability, swelling measurements, In Vitro enzymatic degradation measurements and tensile test. The composite scaffolds showed pore sizes from 125 μm to 175 μm, good interconnectivity between pores and suitable porosity which are desirable for cell growth. The addition of chitosan-gelatin to silk fibroin increased water uptake and degradation rate and reduced mechanical strength but silk fibroin affect reversely on the degradation and mechanical strength of composite scaffolds. Biocompatibility of scaffolds was demonstrated by MTT-assay and hematoxylin-eosin (H&E) staining which lead to the growth and adhesion of endothelial cells. In this study, the fabricated composite scaffolds have the potential for tissue engineering applications

Development of meniscus cartilage using polycaprolactone and decellularized meniscus surface modified by gelatin, hyaluronic acid biomacromolecules: A rabbit model

The lack of vascularization in the white-red and white zone of the meniscus causes these zones of tissue to have low self-healing capacity in case of injury and accelerate osteoarthritis (OA). In this study, we have developed hybrid constructs using polycaprolactone (PCL) and decellularized meniscus extracellular matrix (DMECM) surface modified by gelatin (G), hyaluronic acid (HU) and selenium (Se) nanoparticles (PCL/DMECM/G/HU/Se), following by the cross-linking of the bio-polymeric surface. Material characterization has been performed on the fabricated scaffold using scanning electron microscopy (SEM), Fourier transforms infrared (FTIR) spectroscopy, swelling and degradation analyses, and mechanical tests. In Vitro, investigations have been conducted by C28/I2 human chondrocyte culture into the scaffold and evaluated the cytotoxicity and cell/scaffold interaction. For the in vivo study, the scaffolds were transplanted into the defect sites of female New Zealand white rabbits. Good regeneration was observed after two months. We have concluded that the designed PCL/DMECM/G/HU construct can be a promising candidate as a meniscus tissue engineering scaffold to facilitate healing

Curcumin: footprints on cardiac tissue engineering

Introduction: Curcumin-based products are extensively used as therapeutics in the treatment of cardiac disorders; however, there is no significant report on the curcumin potentials in cardiac tissue engineering applications. Due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties, curcumin has been demonstrated to be a promising candidate for tissue engineering (TE) applications. Areas covered: Various curcumin-containing tissue-engineered constructs have been developed for the management of soft tissue damages (such as wound injuries); hence, there are hopes for the use of this natural product in cardiac tissue engineering (CTE). However, some crucial issues should primarily be addressed before curcumin could be widely used in CTE. Expert opinion: The challenges regarding the use of curcumin in CTE include the optimum dosages of curcumin for promoting cardiac regeneration, the type of carrier used (e.g., polymeric matrices), the preferable release profile, as well as the short- and long-term toxicity in the human body. keywords: biomaterialscardiac patchescardiac tissue engineeringCurcuminregenerative medicinescaffoldstissue engineerin

Stem cell-based therapies for cardiac diseases: The critical role of angiogenic exosomes

Finding effective treatments for cardiac diseases is among the hottest subjects in medicine; cell-based therapies have brought great promises for managing a broad range of life-threatening heart complications such as myocardial infarction. After clarifying the critical role of angiogenesis in tissue repair and regeneration, various stem/progenitor cell were utilized to accelerate the healing of injured cardiac tissue. Embryonic, fetal, adult, and induced pluripotent stem cells have shown the appropriate proangiogenic potential for tissue repair strategies. The capability of stem cells for differentiating into endothelial lineages was initially introduced as the primary mechanism involved in improving angiogenesis and accelerated heart tissue repair. However, recent studies have demonstrated the leading role of paracrine factors secreted by stem cells in advancing neo-vessel formation. Genetically modified stem cells are also being applied for promoting angiogenesis regarding their ability to considerably overexpress and secrete angiogenic bioactive molecules. Yet, conducting further research seems necessary to precisely identify molecular mechanisms behind the proangiogenic potential of stem cells, including the signaling pathways and regulatory molecules such as microRNAs. In conclusion, stem cells' pivotal roles in promoting angiogenesis and consequent improved cardiac healing and remodeling processes should not be ignored, especially in the case of stem cell-derived extracellular vesicles

Preparation and in vitro characterization of electrospun scaffolds composed of chitosan, gelatin and 58S bioactive glass nanoparticles for skin tissue engineering

Background and aims: The presence of an appropriate scaffold at the wound site could significantly improve the healing process. In this study, we aimed to prepare a biomimetic nanocomposite scaffold composed of chitosan, gelatin, and 58S bioglass nanoparticles for skin tissue engineering. Methods: The nanocomposite scaffolds composed of chitosan, gelatin, and 58S bioglass nanoparticles were fabricated through electrospinning process. Then the cell viability assay was performed in order to evaluate the biological properties of the membranes. The optimum concentration of bioglass nanoparticles was determined for further studies. In vitro characterization was also performed to evaluate physicochemical properties of the scaffolds. Results: The chitosan/gelatin scaffold containing 2% of 58S bioglass nanoparticles showed no cell toxicity, and the dermal fibroblasts were found capable of proliferation on the membrane. The in vitro results obtained from the scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and porosity tests demonstrated the appropriate properties of the membrane as a scaffold for skin regeneration. Conclusions: It was concluded that a chitosan-gelatin membrane containing 2% of 58S bioglass nanoparticles had the potential to function as a scaffold to accelerate wound healing due to its suitable properties, such as high porosity, high surface/volume ratio, and excellent biocompatibility. Keywords: Chitosan, Gelatin, Bioactive glass, Wound healing, Tissue engineerin

Fabrication of functional and nano-biocomposite scaffolds using strontium-doped bredigite nanoparticles/polycaprolactone/poly lactic acid via 3D printing for bone regeneration

Bone tissue engineering is a field to manufacture scaffolds for bone defects that cannot repair without medical interventions. Ceramic nanoparticles such as bredigite have importance roles in bone regeneration. We synthesized a novel strontium (Sr) doped bredigite (Bre) nanoparticles (Bre-Sr) and then developed new nanocomposite scaffolds using polycaprolactone (PCL), poly lactic acid (PLA) by the 3D-printing technique. Novel functional nanoparticles were synthesized and characterized using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and energy dispersive spectroscopy (EDS: map). The nanoparticles were uniformly distributed in the polymer matrix composites. The 3D- printed scaffolds were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), attenuated total reflection-fourier transform infrared (ATR-FTIR), degradation rate porosity, mechanical tests, apatite formation and cell culture. Degradation rate and mechanical strength were increased in the PLA/PCL/Bre-5%Sr nanocopmposite scaffolds. Hydroxyapatite crystals were also created on the scaffold surface in the bioactivity test. The scaffolds supported viability and proliferation of human osteoblasts. Gene expression and calcium deposition in the samples containing nanoparticles indicated statistical different than the scaffolds without nanoparticles. The nanocomposite scaffolds were implanted into the critical-sized calvarial defects in rat for 3 months. The scaffolds containing Bre-Sr ceramic nanoparticles exhibited the best potential to regenerate bone tissue

Characterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair

Objective Meniscus injuries in the inner avascular zone have weak intrinsic self-healing capacity and often progress to osteoarthritis. This study focused on evaluating the effects of polycaprolactone/silk fibroin/gelatin/ascorbic acid (PCL/SF/Gel/AA) composite scaffolds seeded with adipose-derived mesenchymal stem cells (ASCs), in the meniscus repair. Design To this end, composite scaffolds were cross-linked using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride. Scaffolds were then characterized by scanning electron microscope, mechanical tests, total antioxidant capacity, swelling, and toxicity tests. Results The PCL/SF/Gel/AA scaffolds exhibited suitable mechanical properties. Furthermore, vitamin C rendered them the highest antioxidant capacity. The PCL/SF/Gel/AA scaffolds also showed good biocompatibility and proliferation for chondrocytes. Moreover, the PCL/SF/Gel/AA scaffold seeded with allogeneic ASCs was engrafted in New Zealand rabbits who underwent unilateral punch defect in the medial meniscus of the right knee. After 2 months postimplantation, macroscopic and histologic studies for new meniscus cartilage were performed. Conclusions Our results indicated that the PCL/SF/Gel/AA composite scaffolds seeded with allogeneic ASCs could successfully improve meniscus healing in damaged rabbits