Multicomponent Hydrogels for the Formation of Vascularized Bone-like Constructs In Vitro

Derkus, Burak; Okesola, Babatunde O.; Barrett, David W.; D'Este, Matteo; Chowdhury, Tina T.; Eglin, David; Mata, Alvaro

Abstract

The native extracellular matrix (ECM) is a complex gel-like system with a broad range of structural features and biomolecular signals. Hydrogel platforms that can recapitulate the complexity and signaling properties of this ECM would have enormous impact in fields ranging from tissue engineering to drug discovery. Here, we report on the design, synthesis, and proof-of-concept validation of a microporous and nanofibrous hydrogel exhibiting multiple bioactive epitopes designed to recreate key features of the bone ECM. The material platform integrates self-assembly with orthogonal enzymatic cross-linking to create a supramolecular environment comprising hyaluronic acid modified with tyramine (HA-Tyr) and peptides amphiphiles (PAs) designed to promote cell adhesion (RGDS-PA), osteogenesis (Osteo-PA), and angiogenesis (Angio-PA). Through individual and co-cultures of human adipose derived mesenchymal stem cells (hAMSCs) and human umbilical vascular endothelial cells (HUVECs), we confirmed the capacity of the HA-Tyr/RGDS-PA/Osteo-PA/Angio-PA hydrogel to promote cell adhesion as well as osteogenic and angiogenic differentiation in both 2D and 3D setups. Furthermore, using immunofluorescent staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), we demonstrated co-differentiation and organization of hAMSCs and HUVECs into 3D aggregates resembling vascularized bone-like constructs.

Citation

Derkus, B., Okesola, B. O., Barrett, D. W., D'Este, M., Chowdhury, T. T., Eglin, D., & Mata, A. (2020). Multicomponent Hydrogels for the Formation of Vascularized Bone-like Constructs In Vitro. Acta Biomaterialia, 109, 82-94. https://doi.org/10.1016/j.actbio.2020.03.025

• Journal Article Type: Article
• Acceptance Date: Mar 18, 2020
• Online Publication Date: Apr 18, 2020
• Publication Date: 2020-06
• Deposit Date: Apr 21, 2020
• Publicly Available Date: Apr 19, 2021
• Journal: Acta Biomaterialia
• Print ISSN: 1742-7061
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 109
• Pages: 82-94
• DOI: https://doi.org/10.1016/j.actbio.2020.03.025
• Keywords: Biotechnology; Biochemistry; Molecular Biology; Biomaterials; Biomedical Engineering; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4325080
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S1742706120301665