The landscape of clinical trials in corneal regeneration: A systematic review of tissue engineering approaches in corneal disease.

The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio-based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio-based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio-based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio-based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models.

Correction: ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects.

Correction for 'ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects' by Safieh Boroumand et al., Biomater. Sci., 2024, https://doi.org/10.1039/d4bm00129j.

ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects.

Corneal transplantation is the gold standard treatment for corneal-related blindness; however, this strategy faces challenges such as limited donor cornea, graft rejection, suture-related complications, and the need for specialized equipment and advanced surgical skills. Development of tissue adhesives for corneal regeneration is of great clinical value. However, currently available corneal tissue sealants pose challenges, such as lack of safety, biocompatibility, and desired mechanical properties. To meet these requirements simultaneously, a bovine stromal corneal extracellular matrix (dCor) was used to design a bioadhesive photocurable hydrogel based on gelatin methacrylate (GelMA) and polyethylene glycol diacrylate (PEGDA) hydrogels (dCor/Gel-PEG). Integration of dCor into the dual networks of GelMA and PEGDA (Gel-PEG) led to a bioadhesive hydrogel for curing corneal defects, which could be crosslinked by Irgacure 2959 within 5 min ultraviolet irradiation. The viability of corneal stromal stem cells (CSSCs) was improved on the dCor/Gel-PEG hydrogel in comparison to the Gel-PEG hydrogel. The gene expression profile supported the keratocyte differentiation of CSSCs seeded on dCor/Gel-PEG via increased KERA and ALDH, with inhibited myofibroblast transdifferentiation via decreased α-SMA due to the presence of dCor. Interestingly, the dCor/Gel-PEG hydrogel exhibited favorable mechanical performance in terms of elasticity and bioadherence to the host corneal stroma. Ex vivo and in vivo examinations proved the feasibility of this hydrogel for the sutureless reconstruction of deep anterior corneal defects with promising histopathological results.

Nanoscale vibration could promote tenogenic differentiation of umbilical cord mesenchymal stem cells.

Regulation of mesenchymal stem cell (MSC) fate for targeted cell therapy applications has been a subject of interest, particularly for tissues such as tendons that possess a marginal regenerative capacity. Control of MSCs' fate into the tendon-specific lineage has mainly been achieved by implementation of chemical growth factors. Mechanical stimuli or 3-dimensional (D) scaffolds have been used as an additional tool for the differentiation of MSCs into tenocytes, but oftentimes, they require a sophisticated bioreactor or a complex scaffold fabrication technique which reduces the feasibility of the proposed method to be used in practice. Here, we used nanovibration to induce the differentiation of MSCs toward the tenogenic fate solely by the use of nanovibration and without the need for growth factors or complex scaffolds. MSCs were cultured on 2D cell culture dishes that were connected to piezo ceramic arrays to apply nanovibration (30-80 nm and 1 kHz frequency) over 7 and 14 d. We observed that nanovibration resulted in significant overexpression of tendon-related markers in both gene expression and protein expression levels, while there was no significant differentiation into adipose and cartilage lineages. These findings could be of assistance in the mechanoregulation of MSCs for stem cell engineering and regenerative medicine applications.

Aloe Vera/Collagen Mixture Induces Integrin α1ß1 and PECAM-1 Genes Expression in Human Adipose-Derived Stem Cells.

Purpose: Natural biomaterials are a key base in tissue engineering, and collagen, as the main content of the extracellular matrix (ECM), is frequently used in tissue engineering. Aloe vera has some therapeutic effects on ulcers, therefore, the use of this natural resource has always been considered for improving collagen function. We aimed to evaluate the effect of Aloe vera/ Collagen blended on cell viability, cell attachment, and angiogenic potential by determining of integrin α1ß1 and platelet endothelial cell adhesion molecule (PECAM-1) genes expression in human adipose-derived stem cells (hASCs). Methods: In this study, hASCs after harvesting of adipose tissues from abdominal subcutaneous adipose tissue and isolation, were cultured in four groups of control, collagen gel, Aloe vera gel, and Aloe vera/collagen blended in vitro environment at 24h and then cell viability was assessed by MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium) assay. Integrin α1ß1 and PECAM-1 genes expression were evaluated by real-time RT-PCR. Results: The results of MTT showed that the combination of Aloe vera/collagen was retained the cell viability at the normal range and improved it. In real-time RT-PCR results, integrin α1ß1 and PECAM-1 gene expression were increased in the Aloe vera/collagen blended group compared to the control group. Conclusion: For tissue engineering purposes, Aloe vera improves collagen properties in the culture of hASCs by increasing the expression of the integrin α1ß1 and PECAM-1 genes.

Tumor-derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy.

Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression and invasion, one of these strategies has been shown to be the release of exosomes. Exosomes are small nanovesicles secreted by all kind of cells in the body, especially cancer cells, and mediate cell to cell communications. Exosomes play an important role in cancer invasiveness by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their function in the body. Then, we will focus on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular emphasis on the underlying mechanisms in various cancer origins. Also, exosomes derived from stem cells and tumor-associated macrophages will be discussed in this regard. Finally, we will discuss the novel therapeutic strategies of exosomes as drug delivery vehicles against angiogenesis.