The Evolution of Fabrication Methods in Human Retina Regeneration

Optic nerve and retinal diseases such as age-related macular degeneration and inherited retinal dystrophies (IRDs) often cause permanent sight loss. Currently, a limited number of retinal diseases can be treated. Hence, new strategies are needed. Regenerative medicine and especially tissue engineering have recently emerged as promising alternatives to repair retinal degeneration and recover vision. Here, we provide an overview of retinal anatomy and diseases and a comprehensive review of retinal regeneration approaches. In the first part of the review, we present scaffold-free approaches such as gene therapy and cell sheet technology while in the second part, we focus on fabrication techniques to produce a retinal scaffold with a particular emphasis on recent trends and advances in fabrication techniques. To this end, the use of electrospinning, 3D bioprinting and lithography in retinal regeneration was explored.

Dissemination of Biomedical Cell Sheets using Reality Technology and Digital Tools

Nowadays, with the advance of biomedical and pharmaceutical technology, new treatments such as cell therapy, cell sheets, etc. all provide patients other alternatives. However, the public has little knowledge in these new technologies and they also find them difficult to understand. Hence, this paper is aimed at providing the public with state-of-the-art technological knowledge and constructing an innovative field full of diversity, entertainment, and educational meaning with the assistance of Augmented Reality (AR) and Virtual Reality (VR). Taking the cell sheets technology, a kind of cell therapy recently approved in Taiwan, as an example, we built an AR platform, and demonstrated a trailer animation, 2D animation and 3D model animation via Merge Cube. The trailer animation will portrait how the main character helps her friend, who became physically challenged in an accident, stand up again by asking a genius doctor to perform cell sheet technology. The 2D animation will be used to explain how cell sheet works and its application, while the 3D animation helps demonstrate the DNA reproduction and cell division in cell therapy. A VR field will also be set up so that players can play as the genius doctor, fight their way through the VR games, and learn more about cell sheet technology. To let the public learn more about this biotechnology knowledge, we held an exhibition to display the research results, providing them a whole new learning experience.

Fundamental Technologies and Recent Advances of Cell-Sheet-Based Tissue Engineering

Tissue engineering has attracted significant attention since the 1980s, and the applications of tissue engineering have been expanding. To produce a cell-dense tissue, cell sheet technology has been studied as a promising strategy. Fundamental techniques involving tissue engineering are mainly introduced in this review. First, the technologies to fabricate a cell sheet were reviewed. Although temperature-responsive polymer-based technique was a trigger to establish and spread cell sheet technology, other methodologies for cell sheet fabrication have also been reported. Second, the methods to improve the function of the cell sheet were investigated. Adding electrical and mechanical stimulation on muscle-type cells, building 3D structures, and co-culturing with other cell species can be possible strategies for imitating the physiological situation under in vitro conditions, resulting in improved functions. Finally, culture methods to promote vasculogenesis in the layered cell sheets were introduced with in vivo, ex vivo, and in vitro bioreactors. We believe the present review that shows and compares the fundamental technologies and recent advances for cell-sheet-based tissue engineering should promote further development of tissue engineering. The development of cell sheet technology should promote many bioengineering applications.

Fabrication of hyaline-like cartilage constructs using mesenchymal stem cell sheets

Cell and tissue engineering approaches for articular cartilage regeneration increasingly focus on mesenchymal stem cells (MSCs) as allogeneic cell sources, based on availability and innate chondrogenic potential. Many MSCs exhibit chondrogenic potential as three-dimensional (3D) cultures (i.e. pellets and seeded biomaterial scaffolds) in vitro; however, these constructs present engraftment, biocompatibility, and cell functionality limitations in vivo. Cell sheet technology maintains cell functionality as scaffold-free constructs while enabling direct cell transplantation from in vitro culture to targeted sites in vivo. The present study aims to develop transplantable hyaline-like cartilage constructs by stimulating MSC chondrogenic differentiation as cell sheets. To achieve this goal, 3D MSC sheets are prepared, exploiting spontaneous post-detachment cell sheet contraction, and chondrogenically induced. Results support 3D MSC sheets’ chondrogenic differentiation to hyaline cartilage in vitro via post-contraction cytoskeletal reorganization and structural transformations. These 3D cell sheets’ initial thickness and cellular densities may also modulate MSC-derived chondrocyte hypertrophy in vitro. Furthermore, chondrogenically differentiated cell sheets adhere directly to cartilage surfaces via retention of adhesion molecules while maintaining the cell sheets’ characteristics. Together, these data support the utility of cell sheet technology for fabricating scaffold-free, hyaline-like cartilage constructs from MSCs for future transplantable articular cartilage regeneration therapies.

Novel pre-vascularized tissue-engineered dermis based on stem cell sheet technique used for dermis-defect healing

Insufficient donor dermis and the shortage of three-dimensional vascular networks are the main limitations in the tissue-engineered dermis (TED). To solve these problems, we initially constructed pre-vascularized bone marrow mesenchymal stem cell sheet (PBMCS) and pre-vascularized fibroblasts cell sheet (PFCS) by cell sheet technology, and then superimposed or folded them together to construct a pre-vascularized TED (PTED), aiming to mimic the real dermis structure. The constructed PTED was implanted in nude mice dorsal dermis-defect wound and the wound-healing effect was quantified at Days 1, 7 and 14 via the methods of histochemistry and immunohistochemistry. The results showed that PTED could rapidly promote the wound closure, especially at Day 14, and the wound-healing rate of three-layer PTED could reach 97.2% (P < 0.01), which was faster than the blank control group (89.1%), PBMCS (92.4%), PFCS (93.8%) and six-layer PTED (92.3%). In addition, the vessel density in the PTED group was higher than the other groups on the 14th day. Taken together, it is proved that the PTED, especially three-layer PTED, is more conducive to the full-thickness dermis-defect repair and the construction of the three-dimensional vascular networks, indicating its potential application in dermis-defect repair.