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Published on: June 16, 2022
Macromolecular modulation of a 3D hydrogel construct differentially regulates human stem cell tissue-to-tissue
Diana R Pereira1, Joana Silva-Correia2, Joaquim M Oliveira2
13B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal; CÚRAM SFI Research Centre for Medical Devices, National University of Ireland, Galway, Ireland.
Abstract:
The simultaneous generation of multiple tissues and their functional assembly into complex tissues remains a critical challenge for regenerative medicine. The tissue-to-tissue interface connecting two adjacent tissues is vital in effective tissue function. The presented worked hypothesize that differential functional property can be engineered by modulating the macromolecular composition of a 3D hydrogel construct and distinctively endow stem cell fate. Hence, it was possible to successfully generate macromolecular constructs by using the extracellular matrix (ECM)-based materials; type I collagen (Col I) and hyaluronic acid (HA); and natural-derived biomaterials as methacrylated gellan-gum (GGMA). The 3D hydrogel constructs consisted of two dissimilar layers: 1) Col I: HA hydrogel and 2) GGMA hydrogel. The tissue-to-tissue interface was created by seeding human mesenchymal stem cells (MSCs) between the two layers. Differential functional rheological and mechanical properties characterized the acellular 3D gradient hydrogel constructs. The cell-based 3D hydrogel constructs were assessed for MSCs viability by live/dead staining. Assessing apoptosis by flow cytometry, data showed the feasibility of the 3D hydrogel constructs in maintaining cell viability with no apoptosis induction onto MSCs. A homogeneous distribution was achieved in a successful cellular tissue-to-tissue interface. Human MSCs low proliferative rate and low ECM deposition were seen for all constructs; however, lower proliferative rate within the ECM microenvironment highlights controlled self-renewal of MSCs. The 3D hydrogel constructs maintained the human MSCs phenotype, yet the macromolecular modulation allowed tuning the human MSCs morphology from round to spindle-shaped phenotype. The intrinsic properties of the 3D cell-based hydrogel construct induced differential inflammatory and angiogenic paracrine secretory profiles owing to the dissimilar engineered biophysical milieu. Human MSCs sense the nearby macromolecular environment adjusting the cell-ECM interactions, which influence cell behaviour and fate. Beyond multi-tissue regeneration, the engineered cellular 3D hydrogel constructs may simultaneously address immune regeneration.
