3D bioprinted mesenchymal stem cell laden scaffold enhances subcutaneous vascularization for delivery of cell therapy

IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Biomedical Microdevices Pub Date : 2024-06-18 DOI:10.1007/s10544-024-00713-2
Tommaso Bo, Elia Pascucci, Simone Capuani, Jocelyn Nikita Campa-Carranza, Letizia Franco, Marco Farina, Jacopo Secco, Sara Becchi, Rosanna Cavazzana, Ashley L. Joubert, Nathanael Hernandez, Corrine Ying Xuan Chua, Alessandro Grattoni
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Abstract

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery.

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富含间充质干细胞的三维生物打印支架增强了皮下血管的生成,可用于细胞治疗。
皮下注射细胞疗法是治疗各种疾病的一种极具吸引力的微创策略。然而,皮下部位血管不发达,不足以支持外源细胞的移植、存活和功能。在这项研究中,我们开发了一种由藻酸盐/明胶(Alg/Gel)组成的三维生物打印支架,其中嵌入了间充质干细胞(MSCs),以增强皮下微环境中的血管生成和组织生长。我们确定了可最佳再现皮下组织机械特性的生物墨水交联条件。我们实现了 Alg/Gel 支架的可控降解,与宿主组织的生长和重塑同步。此外,在大鼠模型中,Alg/凝胶支架在支持皮下组织发育和血管形成方面优于间充质干细胞包埋的 Pluronic 水凝胶。虽然单独使用支架能促进血管组织的形成,但在生物墨水中加入间充质干细胞能进一步促进血管生成。我们的研究结果突显了使用简单的含有细胞的可降解生物打印结构为细胞输送提供支持性微环境的重要性。
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来源期刊
Biomedical Microdevices
Biomedical Microdevices 工程技术-工程:生物医学
CiteScore
6.90
自引率
3.60%
发文量
32
审稿时长
6 months
期刊介绍: Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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