A bone-on-a-chip collagen hydrogel-based model using pre-differentiated adipose-derived stem cells for personalized bone tissue engineering

Mesenchymal stem cells have contributed to the continuous progress of tissue engineering and regenerative medicine. Adipose-derived stem cells (ADSC) possess many advantages compared to other origins including easy tissue harvesting, self-renewal potential, and fast population doubling time. As mult...

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Detalhes bibliográficos
Autores: Alamán-Díez, Pilar, García-Gareta, Elena, Arruebo, Manuel, Pérez, María Ángeles
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/343070
Acesso em linha:http://hdl.handle.net/10261/343070
Access Level:acceso abierto
Palavra-chave:ADSC differentiation
Bone-on-a-chip
In vitro bone model
Microfluidics
Descrição
Resumo:Mesenchymal stem cells have contributed to the continuous progress of tissue engineering and regenerative medicine. Adipose-derived stem cells (ADSC) possess many advantages compared to other origins including easy tissue harvesting, self-renewal potential, and fast population doubling time. As multipotent cells, they can differentiate into osteoblastic cell linages. In vitro bone models are needed to carry out an initial safety assessment in the study of novel bone regeneration therapies. We hypothesized that 3D bone-on-a-chip models containing ADSC could closely recreate the physiological bone microenvironment and promote differentiation. They represent an intermedium step between traditional 2D-in vitro and in vivo experiments facilitating the screening of therapeutic molecules while saving resources. Herein, we have differentiated ADSC for 7 and 14 days and used them to fabricate in vitro bone models by embedding the pre-differentiated cells in a 3D collagen matrix placed in a microfluidic chip. Osteogenic markers such as alkaline phosphatase activity, calcium mineralization, changes on cell morphology, and expression of specific proteins (bone sialoprotein 2, dentin matrix acidic phosphoprotein-1, and osteocalcin) were evaluated to determine cell differentiation potential and evolution. This is the first miniaturized 3D-in vitro bone model created from pre-differentiated ADSC embedded in a hydrogel collagen matrix which could be used for personalized bone tissue engineering.