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Stem cells in regenerative medicine: new perspectives

Digestion [30 Jul , 92 2 ]. Abstract The intestinal epithelium exerts multiple, indispensable functions to maintain the homeostasis of our body. Arch Plast Surg ;41 4 Murphy SV, Atala A. Biotechnol ;32 8 Med Nov;1 11 Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study. Lancet ; : Future Perspectives for Regenerative Medicine in Ophthalmology.

Perspectives in Regenerative Medicine | Ena Ray Banerjee | Springer

Middle East Afr. Oph-thalmol ;20 1 Heparin-modified gelatin scaffolds for human corneal endothelial cell transplantation. Biomaterials ;35 13 Stem Cells ;27 7 Song MJ, Bharti K. Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Lancet ; Anthony, Atala. Growing new organs. Table IV.

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Advanced Search Users Online: Regenerative medicine: Clinical applications and future perspectives. J Microsc Ultrastruct ; Specific organs and tissues. PLoS One. Click here to view. B implantation of TEVG.

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The image shows inferior vena cava IVC and aorta Ao. C Survival rate at 24 hours after surgery. D Kaplan-Meier survival curve considering the 12 months of experiment. No significant statistical difference was highlighted between the two groups. Table 1: Some of the commercially available skin substitutes that have been successfully used in clinical practice. Figure 3: Tissue engineered skin construct inserted into the mouse wound after the implantation left and on the 11 th day right , when the wound fully healed.

Patient’s Perspective: The Promise of Regenerative Medicine

Epub Mar 4. Figure 4: MSCs improve corneal wound healing. A—D Fluorescein-stained corneas of the control group show reduced recovery in reference to group treated with MSCs. E Percentage analysis of fluorescein-stained corneas highlights a significant statistical difference between the two groups: MSC group stained in a very lower manner than the control group, confirming the acceleration of corneal wound healing. Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn.

Epub Feb This article has been cited by. Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications. Devising tissue ingrowth metrics: a contribution to the computational characterization of engineered soft tissue healing. To compete with these products, 3D bioprinted skin must have additional properties, mainly functional, or reduced costs to overcome competition in the market.

Not surprisingly, the first successes for 3D bioprinted skin were in the cosmetics industry, which had hitherto been an underexplored market. Beyond the cosmetic industry, 3D bioprinted skin has made modest inroads due to competition from other artificial skin manufacturing methods that have been firmly in place for decades.


Despite some success in adding skin pigmentation and vascularization via bioprinting, innervation and the incorporation of hair follicles remain significant challenges. Thus, achieving fully functional 3D bioprinted skin remains a distant goal. Another critical barrier to skin bioprinting is the associated cost. A cohesive and interdisciplinary effort will be required in future years before this exciting technology can be translated to the clinic on a large scale. Bony tissue is distinct from other tissues in the body by nature of its hardness, and it is this mechanical property that enables the many functions of the skeletal system e.

Cartilage, an elastic but stiff connective tissue found in many areas of the skeletal system, also relies on its mechanical properties for proper function e. Because proper function is contingent on proper mechanics, bone and cartilage regeneration is focused largely on restoring the salient mechanical properties of each tissue type. Both conventional 3D printing and bioprinting are poised to assist in bone and cartilage repair; however, the strategies involved are very different.

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In the following, we review current strategies for bioprinting functional bone and cartilage, recent in vivo studies, clinical translation, and future capabilities. In contrast to creating a non-living bone substitute for providing solely mechanical support, the aim of bioprinting cell-laden bone scaffolds and mimicking the in vivo cellular microenvironment is to achieve proper function and restore tissue-level integrity [1]. Regeneration utilizes mainly stem cells with osteogenic potency, since human osteoblast cell lines are limited in availability.

Amongst different stem cell sources, human mesenchymal stem cells MSCs have shown excellent potential for bone regeneration. Other than choosing the appropriate cell type, three other major factors also need to be considered: biomaterials , soluble biomolecules , and cell-cell interactions.

Perspectives in Regenerative Medicine

A variety of biomaterials have been assessed, including printed collagen-hydroxyapatite scaffolds seeded with human MSCs that have shown osteogenic outcome in vitro and enhanced bone repair in a rabbit model [44]. Following this work, Heo et al. The PLA hydrogel imparted improved mechanical properties, while RGD nanoparticles promoted cell adhesion and osteogenic stem cell differentiation [45]. Other researchers have reported that adding agarose a stiff thermo-responsive hydrogel to collagen a natural cell-adhesive hydrogel significantly improved the mechanical properties and promoted osteogenic differentiation of human MSCs [46]. Taken together, these advances highlight the importance of considering both mechanical and biological properties of biomaterials for facilitating osteogenesis.

In vitro bioprinted models are just as well established for chondrocytes as they are for osteocytes. One of the earliest studies on cartilage bioprinting was conducted in —chondrocytes were bioprinted in poly ethylene glycol dimethacrylate PEGDMA , an FDA-approved synthetic material [47] ; several parameters, including stiffness and methods of crosslinking, were optimized to promote chondrocyte function as indicated by the glycosaminoglycan content. Later studies were performed to examine systematically the effects of bioinks for printing chondrocytes.

Alginate-nanocellulose [48,49] , HA [50] , and gelatin methacrylate GelMA [51,52] all showed superior performance for maintaining long-term viability and functionality of chondrocytes in vitro. Subsequently, Daly et al. Recently, a new type of biomaterial named silk fibroin methacrylate SilMA was developed and applied in 3D bioprinting of cartilage-like constructs [55]. Compared to the natural and synthetic materials described above, SilMA delivered comparable strength but also allowed for tunable stiffness. Furthermore, SilMA demonstrated suitable cell adhesion, providing a promising solution for fabricating hard tissue scaffolds.

In summary, biomaterials are the basis for bioinks and dominate the mechanical properties of the bioink. Selecting a biomaterial that closely mimics the in vivo microenvironment of target tissues is a critical design aspect for bioprinting and regenerating bone and cartilage. Biomolecules, such as growth factors, and their proper integration also play an important role in tissue regeneration.

However, few studies have investigated their role in 3D bioprinting. In , Park et al. Using extrusion bioprinting, the authors spatially defined the distribution of bone morphogenetic protein 2 BMP-2 and vascular endothelial growth factor VEGF to promote bone differentiation and angiogenesis, respectively.

Printed scaffolds with these spatially defined growth factors were seeded with human dental pulp stem cells, which have osteogenic and vasculogenic potential, and implanted in mice and analyzed after 28 days. A significant extent of newly formed microvessels in areas containing VEGF was observed, with better bone regeneration seen in BMP-2 scaffolds.

In addition to growth factors, a recent study examined the effects of encapsulated plasmid DNA on osteogenesis [58]. Enhanced bone matrix deposition and mineralization were observed with the help of plasmid DNA both in vitro and in vivo. These studies highlight the importance of incorporating proper biomolecules in the bioprinting process and releasing them in a controlled manner in order to achieve biomimetic heterogeneity and authentic tissue regeneration.

The last ingredient for mimicking the in vivo native microenvironment for effective tissue regeneration is cell-cell interaction. Incorporating cell-cell interaction in 3D bioprinting requires access to multiple cell types and a complicated multi-nozzle bioprinter, which has made this area of research the most difficult to explore. Kolesky et al.

HUVECs were founds to improve vascularization and permeability for enhanced diffusion, which facilitated long-term 45 days culture of the construct in vitro. Another multiple cell type bioprinting endeavor used a low-cost strategy to facilitate cell-cell interactions via cell-laden cylindrical construct [59].