Engineering principles for guiding spheroid function in the regeneration of bone, cartilage, and skin

Abstract

There is a critical need for strategies that effectively enhance cell viability and post-implantation performance in order to advance cell-based therapies. Spheroids, which are dense cellular aggregates, overcome many current limitations with transplanting individual cells. Compared to individual cells, the aggregation of cells into spheroids results in increased cell viability, together with enhanced proangiogenic, anti-inflammatory, and tissue-forming potential. Furthermore, the transplantation of cells using engineered materials enables localized delivery to the target site while providing an opportunity to guide cell fate in situ, resulting in improved therapeutic outcomes compared to systemic or localized injection. Despite promising early results achieved by freely injecting spheroids into damaged tissues, growing evidence demonstrates the advantages of entrapping spheroids within a biomaterial prior to implantation. This review will highlight the basic characteristics and qualities of spheroids, describe the underlying principles for how biomaterials influence spheroid behavior, with an emphasis on hydrogels, and provide examples of synergistic approaches using spheroids and biomaterials for tissue engineering applications.

Evaluation of scaffold microstructure and comparison of cell seeding methods using micro-computed tomography-based tools

“…Particle sizes up to 200 µm can be considered the most relevant for studying cell seeding as this range allows the use of small cell aggregates for seeding as well. Dense cell aggregates, or spheroids, are known to result in increased tissue formation and cell viability compared with individual cells [34,35]. For comparison, in a previous report, the size of fixed hASCs ranged from 5 to 40 µm with an average diameter of 22 µm [36].…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Cell‐rich 3D clusters fabrication takes advantage of intercellular adhesion mechanisms (e.g., cadherin and integrin‐mediated) to create self‐assembled structures comprising single, or multiple cell types, unlocking the potential to fabricate heterotypic cell constructs more similar to the cellular heterogeneity of human tissues . Upon in vitro maturation, these seamless 3D microaggregates secrete de novo ECM frameworks in which cells reside and exchange interactions, adding to their biofunctionality and biomedical applicability.…”

“…To date, advanced monotypic (single culture) and heterotypic (co‐culture) scaffold‐free 3D multicellular spheroids have been developed as in vitro microphysiological systems for modeling pathophysiology of human diseases or as unitary building blocks for tissue engineering of cardiac, hepatic, vascular, or neuronal tissues, among others . In the context of tissue engineering and regeneration, 3D spheroids have been employed as angiogenic stimulating units (i.e., via secretion of trophic factors—VEGF, PDGF) or as functional blocks for the assembly of prevascularized microtissues . Progresses in this field indicate that 3D spheroids comprising heterogeneous cell populations better recapitulate the complexity of human tissues and exhibit a more pro‐regenerative capacity.…”

“…Also, the spherical morphology restricts the geometrical complexity of fabricated 3D multiscale microtissue assemblies . For bioengineering larger and more intricately patterned tissues, 3D cell‐rich spherical aggregates must be processed through advanced methodologies . In this sense, researchers are advancing 3D spheroids postproduction bioprocessing by using microplatforms that promote spheroid‐spheroid fusion and by taking advantage of automated biofabrication technologies (e.g., 3D bioprinting) that build‐up spheroid‐based living architectures with user‐defined geometries …”

Surface modification of plant-based microparticles for colloidal science and cellular adhesion applications

“…Bee pollen are consumed as functional foods because it contains numerous nutrients, vitamins and minerals [36,37]. Numerous studies have reported that bee pollen contains phenolic acids, kaempferol, palmitic, linoleic acids, calcium, sodium, potassium, and vitamin B, C and E [38,39]. Bee pollen has been studied in apitherapy which is a branch of alternative medicine that mainly uses honey bee products such as honey, pollen, bee venom, etc.…”