Decellularized Extracellular Matrix for Remodeling Bioengineering Organoid's Microenvironment

Zhu, Liye; Yuhan, Jieyu; Yu, Hao; Zhang, Boyang; Huang, Kunlun; Zhu, Longjiao

doi:10.1002/smll.202207752

Cited by 26 publications

(12 citation statements)

References 129 publications

(150 reference statements)

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“…Obtaining an acellular matrix from liposuction is feasible, and fatderived acellular hydrogels have been shown to promote both adipocyte differentiation and vascularization (Getova et al, 2019;Kayabolen et al, 2017;Lee et al, 2021;Liu et al, 2021). While the mechanisms by which extracellular matrices play roles in stem cell differentiation and fate determination remain unclear, they retain physical signals such as spatial topological structures, stiffness, adhesion, elasticity, and bioactive molecules including endogenous growth factors (Liu et al, 2023;Zhu et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

Quan,

Li,

Cai

et al. 2024

Journal Cellular Physiology

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Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light‐crosslinking. We used human white adipose tissue‐derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel. We found that BAOs cultivated in AAM hydrogels with high stiffness demonstrated increased metabolic activity and upregulation of thermogenesis‐related genes. When transplanted into obese and type 2 diabetes mice, the HFD + BAO group showed sustained improvements in metabolic rate, resulting in significant weight loss and decreased blood glucose levels. Furthermore, the mice showed a marked reduction in nonalcoholic liver steatosis, indicating improved liver function. In contrast, transplantation of 2D‐cultured beige adipocytes failed to produce these beneficial effects. Our findings demonstrate the feasibility of fabricating beige adipose organoids in vitro and administering them by injection, which may represent a promising therapeutic approach for obesity and diabetes.

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Section: Discussionmentioning

confidence: 99%

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

Quan,

Li,

Cai

et al. 2024

Journal Cellular Physiology

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“…Given that dECMs change in response to altered environments, determining whether they can be used as a basis for clinical research is necessary. Despite the numerous challenges, dECM remains a potentially ideal substrate for organoid construction [ 138 ].…”

Section: Exploring Modes Of Organoid Engineering: Prospects For Devel...mentioning

confidence: 99%

Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction

Jin,

Xue,

Liu

et al. 2024

Biomater Res

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Tissue damage and functional abnormalities in organs have become a considerable clinical challenge. Organoids are often applied as disease models and in drug discovery and screening. Indeed, several studies have shown that organoids are an important strategy for achieving tissue repair and biofunction reconstruction. In contrast to established stem cell therapies, organoids have high clinical relevance. However, conventional approaches have limited the application of organoids in clinical regenerative medicine. Engineered organoids might have the capacity to overcome these challenges. Bioengineering—a multidisciplinary field that applies engineering principles to biomedicine—has bridged the gap between engineering and medicine to promote human health. More specifically, bioengineering principles have been applied to organoids to accelerate their clinical translation. In this review, beginning with the basic concepts of organoids, we describe strategies for cultivating engineered organoids and discuss the multiple engineering modes to create conditions for breakthroughs in organoid research. Subsequently, studies on the application of engineered organoids in biofunction reconstruction and tissue repair are presented. Finally, we highlight the limitations and challenges hindering the utilization of engineered organoids in clinical applications. Future research will focus on cultivating engineered organoids using advanced bioengineering tools for personalized tissue repair and biofunction reconstruction.

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“…The proliferation and differentiation of DPSCs in the host require an appropriate microenvironment provided by the scaffold material that contains the structural elements necessary for tissue regeneration [7]. Decellularized matrix has a great potential as a scaffold for the bioengineered organoid microenvironment [8,9]. An ideal organoid matrix should possess high biocompatibility, good mechanical properties, degradability, and the ability to simulate the microenvironment to support and enhance cellular activities, such as proliferation, migration and differentiation [10].…”

Section: Introductionmentioning

confidence: 99%

Construction of dental pulp decellularized matrix by cyclic lavation combined with mechanical stirring and its proteomic analysis

Zhang,

Bi,

Huang

et al. 2024

Biomed. Mater.

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The decellularized matrixhas a great potential for tissue remodeling and regeneration; however, decellularization could induce host immune rejection due to incomplete cell removal or detergent residues, thereby posing significant challenges for its clinical application. Therefore, the selection of an appropriate detergent concentration, further optimization of tissue decellularization technique, increased of biosafety in decellularized tissues, and reduction of tissue damage during the decellularization procedures are pivotal issues that need to be investigated. Inthis study, we tested several conditions and determined that 0.1% Sodium dodecyl sulfate(SDS) and three decellularization cycles were the optimal conditions for decellularization of pulp tissue. Decellularization efficiency was calculated and the preparation protocol for dental pulp decellularization matrix (DPDM) was further optimized. To characterize the optimized DPDM, the microstructure, odontogenesis-related protein and fiber content were evaluated. Our results showed that the properties of optimized DPDM were superior to those of the non-optimized matrix. We also performed the 4D-Label-free quantitative proteomic analysis of DPDM and demonstrated the preservation of proteins from the natural pulp. This study provides a solid theoretical and experimental foundation for the potential application of DPDM in pulp regeneration.

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Decellularized Extracellular Matrix for Remodeling Bioengineering Organoid's Microenvironment

Cited by 26 publications

References 129 publications

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction

Construction of dental pulp decellularized matrix by cyclic lavation combined with mechanical stirring and its proteomic analysis

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