Large three-dimensional cell constructs for tissue engineering

Abstract

Much research has been conducted on fabricating biomimetic biomaterials in vitro. Tissue engineering approaches are often conducted by combining cells, scaffolds, and growth factors. However, the degradation rate of scaffolds is difficult to control and the degradation byproducts occasionally limit tissue regeneration. To overcome these issues, we have developed a novel system using a thermo-responsive hydrogel that forms scaffold-free, three-dimensional (3D) cell constructs with arbitrary size and morphology. 3D cell constructs prepared using bone marrow-derived stromal stem cells (BMSCs) exhibited self-organizing ability and formed bone-like tissue with endochondral ossification. Endothelial cells were then introduced into the BMSC construct and a vessel-like structure was formed within the constructs. Additionally, the bone formation ability was promoted by endothelial cells and cell constructs could be freeze-dried to improve their clinical application. A pre-treatment with specific protein protectant allowed for the fabrication of novel bone substitutes composed only of cells. This 3D cell construct technology using thermo-responsive hydrogels was then applied to other cell species. Cell constructs composed of dental pulp stem cells were fabricated, and the resulting construct regenerated pulp-like tissue within a human pulpless tooth. In this review, we demonstrate the approaches for the in vitro fabrication of bone and dental pulp-like tissue using thermo-responsive hydrogels and their potential applications.

Construction of multifunctional cell aggregates in angiogenesis and osteogenesis through incorporating hVE-cad-Fc-modified PLGA/β-TCP microparticles for enhancing bone regeneration

“…5 However, the self-assembly cell-only aggregates have intrinsic limitations in the transport of oxygen and nutrition, and show non-specific differentiation after transplantation, which may hinder their therapeutic efficacy and even cause repair failure. [6][7][8] Blood vessel infiltration provides an optimal microenvironment for nutrient and oxygen supply and removes metabolites, a Department of Pediatric Dentistry, Peking University School and Hospital of hence promoting the viability of MSC aggregates. 9 During the process of bone-tissue regeneration, sufficient angiogenesis facilitates cell proliferation and tissue ingrowth; by contrast, scarce vascular infiltration leads to tissue central necrosis, osseointegration failure and fibrous encapsulation.…”

“…5 However, the self-assembly cell-only aggregates have intrinsic limitations in the transport of oxygen and nutrition, and show non-specific differentiation after transplantation, which may hinder their therapeutic efficacy and even cause repair failure. 6–8…”

The Effects of Transforming Growth Factor-β1 on the Differentiation of Cell Organoids Composed of Gingiva-Derived Stem Cells

“…The important key factors for tissue engineering includes cells, growth factors, and scaffolds [ 28 ]. In a previous report, the combination of bone marrow-derived stem cells and periodontal ligament cells leading to multiphasic constructs produced superior results when compared with gingiva-derived cell sheets [ 29 ].…”

Research Advances on Hydrogel-Based Materials for Tissue Regeneration and Remineralization in Tooth

“…DPSCs were cultured in the space of a hydrogel-based container, and a 3D hollow cylindrically shaped cell cultivation system with a length of 7 mm and a diameter of 3 mm was obtained. After 20 days of culture in vitro, the survival rate of culture cells remained above 85% [ 38 ]. Itoh et al constructed a 3D DPSCs structure with heat-responsive hydrogel, which was filled into the root canal of human teeth and formed endodontic tissue with rich blood vessels after 6 weeks implanted subcutaneously into immunodeficient mice [ 39 ].…”