Effect of TGF-ß3 on wound healing of bone cell monolayer in static and hydrodynamic shear stress conditions.

Introduction: Wound healing is characterized as a complicated and sophisticated biological process through which tissue heals and repairs itself after injury. However, the normal wound healing process relies on different growth factors as well as the presence of an accurate cytokine level to ensure appropriate cellular responses. In the case of wound healing, the effects of various growth factors have been studied, but the effects of transforming growth factor beta (TGF-ß) on wound healing have been found to be more significant because of its broad spectrum of impacts on healing the wounded tissues or skins. Methods: In the current study, the impact of TGF-ß3 in bone cells' wound healing was examined in vitro. Furthermore, the activities and characteristics of TGF-ß3, as well as those of related growth factors throughout this wound healing process, were studied under hydrodynamic shear stress conditions as well as static conditions of cultured bone cells. Results: We demonstrated that a positive outcome of TGF-ß3 treatment was found after 24 h under a static condition, while TGF-ß3 treatment was found to be effective under a dynamic condition for wound closure. In the case of the dynamic condition, a full wound closure was obtained after 18 h in both the control and TGF-ß3 treatment, while in the case of static conditions, wounds were found to remain open, even after 24 h, for both the control and TGF-ß3 treatment. Additionally, in the static condition, the wound closure rate with TGF-ß3 treatment was found to be quicker than that of the control flask, which implies that wound healing can be postponed in the static condition. In the dynamic condition, the wound healing process became more rapid in a cultured cell environment. Conclusion: The synergistic effect of TGF-ß3 and hydrodynamic shear stress conditions had a positive impact on increasing wound healing and improving the rate of wound closure.

Articular Cartilage Injury; Current Status and Future Direction.

Today, treatments of cartilage and osteochondral lesions are routine clinical procedures. The avascular and hard-to-self-repair nature of cartilage tissue has posed a clinical challenge for the replacement and reconstruction of damaged cartilage. Treatment of large articular cartilage defects is technically difficult and complex, often accompanied by failure. Articular cartilage cannot repair itself after injury due to a lack of blood vessels, lymph, and nerves. Various treatments for cartilage regeneration have shown encouraging results, but unfortunately, none have been the perfect solution. New minimally invasive and effective techniques are being developed. The development of tissue engineering technology has created hope for articular cartilage reconstruction. This technology mainly supplies stem cells with various sources of pluripotent and mesenchymal stem cells. This article describes the treatments in detail, including types, grades of cartilage lesions, and immune mechanisms in cartilage injuries.

Pathogenesis of Common Ocular Diseases: Emerging Trends in Extracellular Matrix Remodeling.

The prevalence of visual impairments in human societies is worrying due to retinopathy complications of several chronic diseases such as diabetes, cardiovascular diseases, and many more that are on the rise worldwide. Since the proper function of this organ plays a pivotal role in people's quality of life, identifying factors affecting the development/exacerbation of ocular diseases is of particular interest among ophthalmology researchers. The extracellular matrix (ECM) is a reticular, three-dimensional (3D) structure that determines the shape and dimensions of tissues in the body. The ECM remodeling/hemostasis is a critical process in both physiological and pathological conditions. It consists of ECM deposition, degradation, and decrease/increase in the ECM components. However, disregulation of this process and an imbalance between the synthesis and degradation of ECM components are associated with many pathological situations, including ocular disorders. Despite the impact of ECM alterations on the development of ocular diseases, there is not much research conducted in this regard. Therefore, a better understanding in this regard, can pave the way toward discovering plausible strategies to either prevent or treat eye disorders. In this review, we will discuss the importance of ECM changes as a sentimental factor in various ocular diseases based on the research done up to now.

Reconstruction of Critical Sized Maxillofacial Defects Using Composite Allogeneic Tissue Engineering: Systematic Review of Current Literature.

The current review aimed to assess the reliability and efficacy of tissue-engineered composite grafts in the reconstruction of large maxillofacial defects resulting from trauma or a benign pathologic disease. A systematic review of the literature was conducted using PubMed/Medline, Embase, and Scopus up to March 2022. The eligibility criteria included patients who had been treated with composite allogeneic tissue engineering for immediate/delayed reconstruction of large maxillofacial defects with minimum/no bone harvesting site. In the initial search, 2614 papers were obtained, and finally, 13 papers were eligible to be included in the current study. Most included papers were case reports or case series. A total of 144 cases were enrolled in this systematic review. The mean age of the patients was 43.34 (age range: 9-89). Most studies reported a successful outcome. Bone tissue engineering for the reconstruction and regeneration of crucial-sized maxillofacial defects is an evolving science still in its infancy. In conclusion, this review paper and the current literature demonstrate the potential for using large-scale transplantable, vascularized, and customizable bone with the aim of reconstructing the large maxillofacial bony defects in short-term follow-ups.

Recent Emerging Trend in Stem Cell Therapy Risk Factors.

Different types of stem cells have remarkable characteristics such as high proliferation rate, multi/pluripotency, self-renewal, and broad differentiation that can effectively treat diseases, cancers, and damage. Despite abundant therapeutic applications of stem cells in medical science, numerous risks threaten stem cell transplantation. Tumor development, immune response, cellular senescence, dosage effects, and administration timing are critical risks that should be considered in stem cell therapy. Hence, an investigation of possible risks is required before utilizing stem cell-based medicinal products in the clinical phase and human trials. This review aims to survey the literature and perspectives on the advantages and risks associated with pluripotent and multipotent stem cells.

Retinal Tissue Engineering: Regenerative and Drug Delivery Approaches.

In recent decades, the improvement of photoreceptor-cell transplantation has been used as an effective therapeutic approach to treat retinal degenerative diseases. In this review, the effect of different factors on the differentiation process and stem cells toward photoreceptors along with cell viability, morphology, migration, adhesion, proliferation, and differentiation efficiency is discussed. Scientists are researching to better recognize the reasons for retinal degeneration, as well as discovering novel therapeutic methods to restore lost vision. In this field, several procedures and treatments in the implantation of stem cells-derived retinal cells have been explored for clinical trials. However, the number of these clinical trials is too small to draw sound decisions about whether stem-cell therapies can offer a cure for retinal diseases. Nevertheless, future research directions have started for patients affected by retinal degeneration and promising findings have been obtained.

Anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: A potential biological treatment.

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 µg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.

Bioprinted Membranes for Corneal Tissue Engineering: A Review.

Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed.

Investigation of Cell Adhesion and Cell Viability of the Endothelial and Fibroblast Cells on Electrospun PCL, PLGA and Coaxial Scaffolds for Production of Tissue Engineered Blood Vessel.

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodegradable polymeric scaffolds are a reliable host to adhere and promote proliferation in HUVEC and HVF cells. In particular, PLGA membranes performed much better adhesion and enhanced cell proliferation compared to control in the absence of polymers. In addition, we demonstrate here that these biodegradable membranes present improved mechanical properties to construct potential tissue-engineered vascular graft.

Role of Polymers in Microfluidic Devices.

Polymers are sustainable and renewable materials that are in high demand due to their excellent properties. Natural and synthetic polymers with high flexibility, good biocompatibility, good degradation rate, and stiffness are widely used for various applications, such as tissue engineering, drug delivery, and microfluidic chip fabrication. Indeed, recent advances in microfluidic technology allow the fabrication of polymeric matrix to construct microfluidic scaffolds for tissue engineering and to set up a well-controlled microenvironment for manipulating fluids and particles. In this review, polymers as materials for the fabrication of microfluidic chips have been highlighted. Successful models exploiting polymers in microfluidic devices to generate uniform particles as drug vehicles or artificial cells have been also discussed. Additionally, using polymers as bioink for 3D printing or as a matrix to functionalize the sensing surface in microfluidic devices has also been mentioned. The rapid progress made in the combination of polymers and microfluidics presents a low-cost, reproducible, and scalable approach for a promising future in the manufacturing of biomimetic scaffolds for tissue engineering.

Commercialization and regulation of regenerative medicine products: Promises, advances and challenges.

The ultimate goal of regenerative medicine is to repair, regenerate, or reconstruct functional loss in failed tissues and/or organs. Although regenerative medicine is a relatively new field, multiple diverse research groups are helping regenerative medicine reach its objectives. All endeavors in this field go through in silico, in vitro, in vivo, and clinical trials which are prerequisites to translating such approaches from the bench to the bedside. However, despite such promise, there are only a few regenerative medicine approaches that have actually entered commercialization due to extensive demands for the inclusion of multiple rules, principles, and finances, to reach the market. This review covers the commercialization of regenerative medicine, including its progress (or lack thereof), processes, regulatory concerns, and immunological considerations to name just a few key areas. Also, commercially available engineered tissues, including allografts, synthetic substitutes, and 3D bioprinting inks, along with commercially available cell and gene therapeutic products, are reviewed. Clinical applications and future perspectives are stated with a clear road map for improving the regenerative medicine field.

A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration.

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD-derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD-derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague-Dawley rats without suturing. The intimal SSAD-derived hydrogel, with a pore size of 241.7 ± 21.0 µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD-derived hydrogel, with a pore size of 3.3 ± 1.4 µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD-derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD-derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD-derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

Effect of Nanostructures on the Properties of Glass Ionomer Dental Restoratives/Cements: A Comprehensive Narrative Review.

Overall perspective of nanotechnology and reinforcement of dental biomaterials by nanoparticles has been reported in the literature. However, the literature regarding the reinforcement of dental biomaterials after incorporating various nanostructures is sparse. The present review addresses current developments of glass ionomer cements (GICs) after incorporating various metallic, polymeric, inorganic and carbon-based nanostructures. In addition, types, applications, and implications of various nanostructures incorporated in GICs are discussed. Most of the attempts by researchers are based on the laboratory-based studies; hence, it warrants long-term clinical trials to aid the development of suitable materials for the load bearing posterior dentition. Nevertheless, a few meaningful conclusions are drawn from this substantial piece of work; they are as follows: (1) most of the nanostructures are likely to enhance the mechanical strength of GICs; (2) certain nanostructures improve the antibacterial activity of GICs against the cariogenic bacteria; (3) clinical translation of these promising outcomes are completely missing, and (4) the nanostructured modified GICs could perform better than their conventional counterparts in the load bearing posterior dentition.

Fabrication and Characterization of PCL/PLGA Coaxial and Bilayer Fibrous Scaffolds for Tissue Engineering.

Electrospinning is an innovative new fibre technology that aims to design and fabricate membranes suitable for a wide range of tissue engineering (TE) applications including vascular grafts, which is the main objective of this research work. This study dealt with fabricating and characterising bilayer structures comprised of an electrospun sheet made of polycaprolactone (PCL, inner layer) and an outer layer made of poly lactic-co-glycolic acid (PLGA) and a coaxial porous scaffold with a micrometre fibre structure was successfully produced. The membranes' propriety for intended biomedical applications was assessed by evaluating their morphological structure/physical properties and structural integrity when they underwent the degradation process. A scanning electron microscope (SEM) was used to assess changes in the electrospun scaffolds' structural morphology such as in their fibre diameter, pore size (µm) and the porosity of the scaffold surface which was measured with Image J software. During the 12-week degradation process at room temperature, most of the scaffolds showed a similar trend in their degradation rate except the 60 min scaffolds. The coaxial scaffold had significantly less mass loss than the bilayer PCL/PLGA scaffold with 1.348% and 18.3%, respectively. The mechanical properties of the fibrous membranes were measured and the coaxial scaffolds showed greater tensile strength and elongation at break (%) compared to the bilayer scaffolds. According to the results obtained in this study, it can be concluded that a scaffold made with a coaxial needle is more suitable for tissue engineering applications due to the improved quality and functionality of the resulting polymeric membrane compared to the basic electrospinning process. However, whilst fabricating a vascular graft is the main aim of this research work, the biological data will not present in this paper.

Regenerative Medicine of Liver: Promises, Advances and Challenges.

Liver tissue engineering is a rapidly developing field which combines the novel use of liver cells, appropriate biochemical factors, and engineering principles, in order to replace or regenerate damaged liver tissue or the organ. The aim of this review paper is to critically investigate different possible methods to tackle issues related with liver diseases/disorders mainly using regenerative medicine. In this work the various regenerative treatment options are discussed, for improving the prognosis of chronic liver disorders. By reviewing existing literature, it is apparent that the current popular treatment option is liver transplantation, although the breakthroughs of stem cell-based therapy and bioartificial liver technology make them a promising alternative.

Degradation and Characterisation of Electrospun Polycaprolactone (PCL) and Poly(lactic-co-glycolic acid) (PLGA) Scaffolds for Vascular Tissue Engineering.

The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored by taking each sample out of the PBS solution every week, and the structural changes were investigated under a scanning electron microscope (SEM). The PCL and PLGA scaffolds showed excellent fibre structure with adequate degradation, and the fibre diameter, measured over time, showed slight increase in size. Therefore, as an example of fibre water intake and progressive degradation, the scaffold's percentage weight loss increased each week, further supporting the porous membrane's degradability. The pore size and the porosity percentage of all scaffolds decreased substantially over the degradation period. The conclusion drawn from this experiment is that PCL and PLGA hold great promise for tissue engineering and regenerative medicine applications.

Proof-of-concept study of electrospun PLGA membrane in the treatment of limbal stem cell deficiency.

OBJECTIVE: The aim of this study was to assess the safety of poly-lactic co-glycolic acid (PLGA) electrospun membranes as carriers for limbal tissue explants for treatment of limbal stem cell deficiency (LSCD). METHODS AND ANALYSIS: Approval was obtained for a first in-man study from the Drug Controller General of India. PLGA membranes were applied to the affected eye of five patients after removal of the vascular pannus. Simple limbal epithelial transplantation was performed and limbal explants were secured on the membrane using fibrin glue followed by a bandage contact lens. Patients were followed up for 1 year with ocular exams including slit lamp exam, corneal thickness measurements, intraocular pressure measurements and recording of corneal vascularisation and visual acuity. Systemic examinations included pain grading, clinical laboratory assessment, blood chemistry and urine analysis at baseline, 3 and 6 months after surgery. RESULTS: PLGA membranes completely degraded by 8 weeks post-transplantation without any infection or inflammation. In all five patients, the epithelium regenerated by 3 months. In two in five patients, there was a sustained two-line improvement in vision. In one in five patients, the vision improvement was limited due to an underlying stromal scarring. There was recurrence of pannus and LSCD in two in five patients 6 months after surgery which was not attributable to the membrane. The ocular surface remained clear with no epithelial defects in three in five subjects at 12 months. CONCLUSION: PLGA electrospun membranes show promise as carrier for limbal epithelial cells in the treatment of LSCD.

Stem Cell Niche Microenvironment: Review.

The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN and artificial stem cells for self-renewal.

Efficacy of mesenchymal stromal cells and cellular products in improvement of symptoms for COVID-19 and similar lung diseases.

At the end of 2019, respiratory coronavirus diseases 2019 (COVID-19) appeared and spread rapidly in the world. Besides several mutations, the outcome of this pandemic was the death up to 15% of hospitalized patients. Mesenchymal stromal cell therapy as a therapeutic strategy seemed successful in treatment of several diseases. Not only mesenchymal stromal cells of several tissues, but also their secreted extracellular vesicles and even secretome indicated beneficial therapeutic function. All of these three options were studied for treatment of COVID-19 as well as those respiratory diseases that have similar symptom. Fortunately, most of the outcomes were promising and optimistic. In this paper, we review in-vivo and clinical studies which have been used different sources of mesenchymal stromal cell, secreted extracellular vesicles, and secretome to improve and treat symptoms of COVID-19 and similar lung diseases.

Fabrication of 3D hybrid scaffold by combination technique of electrospinning-like and freeze-drying to create mechanotransduction signals and mimic extracellular matrix function of skin.

Fabrication of extracellular matrix (ECM)-like scaffolds (in terms of structural-functional) is the main challenge in skin tissue engineering. Herein, inspired by macromolecular components of ECM, a novel hybrid scaffold suggested which includes silk/hyaluronan (SF/HA) bio-complex modified by PCP: [polyethylene glycol/chitosan/poly(ɛ-caprolactone)] copolymer containing collagen to differentiate human-adipose-derived stem cells into keratinocytes. In followed by, different weight ratios (wt%) of SF/HA (S1:100/0, S2:80/20, S3:50/50) were applied to study the role of SF/HA in the improvement of physicochemical and biological functions of scaffolds. Notably, the combination of electrospinning-like and freeze-drying methods was also utilized as a new method to create a coherent 3D-network. The results indicated this novel technique was led to ~8% improvement of the scaffold's ductility and ~17% decrease in mean pore diameter, compared to the freeze-drying method. Moreover, the increase of HA (>20wt%) increased porosity to 99%, however, higher tensile strength, modulus, and water absorption% were related to S2 (38.1, 0.32 MPa, 75.3%). More expression of keratinocytes along with growth pattern similar to skin was also observed on S2. This study showed control of HA content creates a microporous-environment with proper modulus and swelling%, although, the role of collagen/PCP as base biocomposite and fabrication technique was undeniable on the inductive signaling of cells. Such a scaffold can mimic skin properties and act as the growth factor through inducing keratinocytes differentiation.