Multicomponent hydrogels for the formation of vascularized bone-like constructs in vitro
Burak Derkus1, Babatunde O Okesola2, David W Barrett2
1Institute of Bioengineering, Queen Mary University of London, E1 4NS London, UK; School of Engineering and Materials Science, Queen Mary University of London, E1 4NS London, UK; Biomedical Engineering Department, Faculty of Engineering, Eskisehir Osmangazi University, 26480 Eskisehir, Turkey; Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey.
Researchers developed a novel bioactive hydrogel that mimics bone extracellular matrix (ECM) properties. This advanced material promotes cell adhesion, osteogenesis, and angiogenesis, creating vascularized bone-like constructs for tissue engineering.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- The native extracellular matrix (ECM) provides complex structural and signaling cues crucial for tissue function.
- Developing biomaterials that recapitulate ECM complexity is vital for advancing tissue engineering and drug discovery.
- Existing hydrogel platforms often lack the intricate features and multiple bioactive signals of native ECM.
Purpose of the Study:
- To design, synthesize, and validate a microporous, nanofibrous hydrogel that mimics key features of the bone ECM.
- To incorporate multiple bioactive epitopes promoting cell adhesion, osteogenesis, and angiogenesis within a single hydrogel platform.
- To create a tunable and reproducible in vitro environment for generating vascularized bone-like constructs.
Main Methods:
- Utilized self-assembly and orthogonal enzymatic cross-linking to create a supramolecular hydrogel environment.
- Modified hyaluronic acid with tyramine (HA-Tyr) and incorporated peptide amphiphiles (PAs) for cell adhesion (RGDS-PA), osteogenesis (Osteo-PA), and angiogenesis (Angio-PA).
- Co-cultured human adipose-derived mesenchymal stem cells (hAMSCs) and human umbilical vascular endothelial cells (HUVECs) in 2D and 3D setups, analyzing differentiation via immunofluorescence and RT-qPCR.
Main Results:
- The HA-Tyr/RGDS-PA/Osteo-PA/Angio-PA hydrogel successfully promoted cell adhesion, osteogenic differentiation, and angiogenic differentiation of hAMSCs and HUVECs.
- Demonstrated co-differentiation and organization of hAMSCs and HUVECs into 3D aggregates resembling vascularized bone-like constructs.
- Confirmed the hydrogel's capacity to induce endothelial cells towards large vascular lumens and MSCs into bone cells within the same platform.
Conclusions:
- This multicomponent, self-assembling bioactive hydrogel provides a sophisticated in vitro environment for cell culture.
- The nanofibrous hydrogel effectively recreates bone ECM features, promoting both osteogenesis and angiogenesis simultaneously.
- The developed strategy offers a promising approach for creating lifelike bone tissue engineering constructs in vitro and potential bone regeneration in vivo.
