Adult Stem Cells Spheroids to Optimize Cell Colonization in Scaffolds for Cartilage and Bone Tissue Engineering

Abstract

Top-down tissue engineering aims to produce functional tissues using biomaterials as scaffolds, thus providing cues for cell proliferation and differentiation. Conversely, the bottom-up approach aims to precondition cells to form modular tissues units (building-blocks) represented by spheroids. In spheroid culture, adult stem cells are responsible for their extracellular matrix synthesis, re-creating structures at the tissue level. Spheroids from adult stem cells can be considered as organoids, since stem cells recapitulate differentiation pathways and also represent a promising approach for identifying new molecular targets (biomarkers) for diagnosis and therapy. Currently, spheroids can be used for scaffold-free (developmental engineering) or scaffold-based approaches. The scaffold promotes better spatial organization of individual spheroids and provides a defined geometry for their 3D assembly in larger and complex tissues. Furthermore, spheroids exhibit potent angiogenic and vasculogenic capacity and serve as efficient vascularization units in porous scaffolds for bone tissue engineering. An automated combinatorial approach that integrates spheroids into scaffolds is starting to be investigated for macro-scale tissue biofabrication.

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

“…Tissue bioengineering represents a new therapeutic alternative for palatal reconstruction, associating the use of stem cells, biomaterials/scaffolds, and signaling molecules. Two main approaches are dominant: the "top-down" approach, in which classically cells are seeded on or into biomaterials for recreating a new 3D tissue in vitro; and the "bottom-up" approach, which uses 3D construction techniques (described in the last section) to improve cell secretion of growth factors for tissue regeneration in vivo (Figure 8; Baptista et al, 2018). Furthermore, Good Manufacturing Practice (GMP) and animal-free supplements are crucial for clinical applications.…”

The Application of Hyaluronic Acid-Based Hydrogels in Bone and Cartilage Tissue Engineering

“…Fibrous cartilage, which possesses higher tissue hardenability, is always generated during the healing process, resulting in long-term performance issues [21][22][23]. To increase the joint function, the formation of natural joint or hyaline cartilage should be promoted instead of fibrous cartilage [23,24]. Disadvantages (i.e., the lack of cartilage cell sources, long harvest times, difficulties with fixing, periosteum hypertrophy and ablation, and poor effects in elderly patients [25][26][27]) remain in autogenous chondrocyte grafts, which have been used for many years.…”

Effect of laser induced topography with moderate stiffness on human mesenchymal stem cell behavior

“…As cells work by nature, they could neither be manipulated nor instructed to exhibit cell behavior in a certain way. Tissue engineers work to mimic cell environments in the body, trick cells to recognize these artificial microenvironments, widely known as scaffold [6,7], and differentiate accordingly as they stay in the body [8][9][10]. Besides cell differentiation, scaffolds properties are also known to have effects on other cell behavior such as proliferation, adhesion and morphology [11].…”