Bioengineering Approaches for the Advanced Organoid Research

Abstract

organoids should exhibit essential features, including organ-specific multiple cell types, functions of the organ, and spatially organized structures. The emergence and progression of organoid technologies have resulted from several important discoveries (Figure 1). The formation of actual tissuelike colonies in vitro was firstly observed from a co-culture system of keratinocytes and 3T3 fibroblasts. [4] Self-organization, one of the fundamental aspects of organogenesis, was first observed via two distinct approaches, namely reaggregation and structural patterning of dissociated single cells. [5,6] The establishment of 3D culture methods for the structural organization began with the development of extracellular matrices (ECM).In the late 1980s, Bissell and colleagues observed that a laminin-rich gel could function as a basement membrane to differentiate and morphogenesis of mammary epithelial cells. [7,8] In the 1990s, it was reported that in addition to their primary role in physical support, ECM components could regulate gene expression by interacting with integrin-based focal adhesion pathways. [9] Finally, in 2009, Clevers group reported that embedding single intestinal stem cells in ECM substitute had created crypt-like structures similar to the epithelium of the native intestinal tissues, which were the first organoids. [10] Based on these recognitions, biochemical cues that include the initiation of lineage-specific genetic programs have been incorporated in 3D organoid cultures. Through exposure to morphogens, growth factors, or morphogen inhibitors, multiple research groups rapidly developed various organoid models using embryonic stem cells (ESCs) or adult stem cells (ASCs); these include intestine, [10] stomach, [11] liver, [12] pancreas, [13] prostate, [14] and brain [15] organoids. At the same time, vascularization techniques were devised by several groups to embody microenvironments that are physiologically close to their actual counterparts. Microfluidic systems, [16] endothelial cell-coated modules, [17] and vascular endothelial growth factor delivery systems [18] have been demonstrated as in vitro vasculature systems that can facilitate oxygen or nutrients transport to the inner mass of organoids.In the late 2010s, owing to the accumulated information on mechanisms underlying organogenesis and the remarkable advancements in the fields of biomaterial and bioengineering, the era of "organoid customization" has begun. Customizable hydrogel matrices have been proposed to form intestinal organoids whose internal networks recapitulate the Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that recapitulate the structural and functional characteristics of native organs. Current organoid technologies have been striding toward identifying the essential factors for controlling the processes involved in organoid development, including physical cues and biochemical signaling. There is a growing demand for engineering dynamic niches characterized by ...

3D Bioprinting of Heterogeneous Constructs Providing Tissue‐Specific Microenvironment Based on Host–Guest Modulated Dynamic Hydrogel Bioink for Osteochondral Regeneration

“…Fabricating a microenvironment that mimics physiological settings, such as incorporating bioactive drugs into the bioprinting process, [ 19 ] or introducing them into the culture of the construct post‐printing determines the regenerative outcomes. [ 20 ] To date, a number of biochemical cues, including the growth factors (e.g., transforming growth factors, bone morphogenetic proteins, and insulin‐like growth factor‐1); small bioactive molecules (e.g., E7 peptide and kartogenin [KGN]); biophysical factors (e.g., chondroitinase ABC and lysyl oxidase‐like 2); and gene therapy, have been demonstrated that could significantly improve the regeneration of osteochondral tissue. [ 19a,21 ] However, due to the lack of drug‐loading groups, the conventional hydrogel bioinks such as GelMA and MeHA generally suffer from the burst release of bioactive drugs where the sustained release of a low dose is favorable for the effective regeneration of osteochondral defects.…”

Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review

“…The construction strategy of organoids is based on the multipotent differentiation and the self-renewal capacity of stem cells. With a deeper understanding of ECM, 3D culture technology can be an effective tool for the structural support of organoids, and the construction methods are diverse and may be customized [ 39 ]. Recently, a range of growth factors and small molecules which simulate the microenvironment of tissue-related stem cells during the process of organogenesis have been revealed.…”

“…One ultimate goal of organoid technology is to construct a bio-smart organoid, which can be well-integrated with native tissues to repair damaged organs. In order to better explore the potential application of organoids, scientists should make further efforts in the development of advanced bio-smart materials together with a deeper understanding of stem cell biology [ 39 ].…”

Lung Cancer Organoids: The Rough Path to Personalized Medicine

“…Moreover, new advances in biomaterial engineering are moving towards an increasing capacity to faithfully recapitulate the heterogeneity of the tumor ECM [ 102 ]. The use of new biomaterials for LCO technology will likely benefit from the advances in 3D culture protocols for normal organoids from lung or other tissues [ 87 , 103 ]. In this regard, a recent report described the use of hyaluronic acid hydrogels for the generation and expansion of iPSC-derived lung alveolar organoids, achieving an increased homogeneity in organoid size and structure [ 104 ].…”