Tissue engineering using traditional size fixed scaffolds and injectable biomaterials are faced with many limitations due to the difficulties of producing macroscopic functional tissues. In this study, 3D functional tissue constructs were developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels. During self-assembly, the accumulation of extracellular matrix (ECM) components was found to strengthen cell-cell and cell-ECM interactions, leading to the construction of a 'native' microenvironment that better preserved cell viability and functions. MSCs grown in self-assembled constructs showed increased maintenance of stemness, reduced senescence and improved paracrine activity compared with cells grown in individual microniches without self-assembly. As an example of applying the self-assembled constructs in tissue regeneration, the constructs were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors. This unique approach of developing self-assembled 3D functional constructs holds great promise for the generation of tissue engineered organoids and repair of challenging tissue defects. STATEMENT OF SIGNIFICANCE: We developed 3D functional tissue constructs using a unique gelatin-based microscopic hydrogel (microcryogels). Mesenchymal stem cells (MSCs) were loaded into gelatin microcryogels to form microscopic cell-laden units (microniches), which were induced to undergo self-assembly using a specially designed 3D printed frame. Extracellular matrix accumulation among the microniches resulted in self-assembled macroscopic constructs with superior ability to maintain the phenotypic characteristics and stemness of MSCs, together with the suppression of senescence and enhanced paracrine function. As an example of application in tissue regeneration, the self-assembled constructs were shown to successfully repair articular cartilage defects without any other supplements. This unique strategy for developing 3D functional tissue constructs allows the optimisation of stem cell functions and construction of biomimetic tissue organoids.

Dan Xing

Wei Liu

Jiao Jiao Li

Longwei Liu

Anqi Guo

Bin Wang

Hongsheng Yu

Yu Zhao

Yuling Chen

Zhifeng You

Cheng Lyu

Wenjing Li

Aifeng Liu

Yanan Du

Jianhao Lin

Acta biomaterialia

ACTA BIOMATERIALIA 是 ELSEVIER 出版的月度同行评审科学期刊。它代表 ACTA MATERIALIA, INC. 出版，由 ASM INTERNATIONAL 和 THE MINERALS, METALS & MATERIALS SOCIETY 赞助。杂志创刊于2005年1月，主编为W.R. WAGNER（匹兹堡大学）。该杂志涵盖生物材料科学的研究，包括从宏观到纳米级的生物材料结构和功能的相互关系。专题报道包括生物医学和生物相容性材料。

Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. It is published on behalf of ACTA MATERIALIA, INC. and sponsored by ASM INTERNATIONAL and THE MINERALS, METALS & MATERIALS SOCIETY. The journal was established in January 2005, with W.R. WAGNER (University of Pittsburgh) as the editor-in-chief. It covers research in biomaterials science, focusing on the relationship between the structure and function of biomaterials at macro to nano scales. Topics include biomedical and biocompatible materials.

《Acta Biomaterialia》是由Elsevier出版的月度同行评审科学期刊。该期刊由ACTA MATERIALIA, INC.出版，并由ASM INTERNATIONAL和THE MINERALS, METALS & MATERIALS SOCIETY赞助。创刊于2005年1月，主编为W.R. WAGNER（匹兹堡大学）。期刊涵盖生物材料科学的研究，探讨生物材料的结构与功能之间的关系，范围从宏观到纳米级。专题报道包括生物医学和生物相容性材料。

Acta Biomaterialia

Acta Biomater

Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.

3D functional tissue constructs developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors.

利用自组装细胞微环境构建3D功能性组织工程结构。

Category	Quartile
医学	1
医学, 工程生物医学	1
医学, 材料科学生物材料	1

Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.

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