Micromolding-Based Encapsulation of Mesenchymal Stem Cells in Biomimetic 3D Microenvironments for Cartilage Regeneration

Nativela F, Smitha A, et al.

Biomaterials Advances

Université de Nantes, ONIRIS, CHU Nantes, INSERM, UCLouvain, INRAE

RESEARCH SUMMARY

This study introduces a micromolding-based approach to encapsulate human mesenchymal stem cells (hMSCs) within biomimetic hyaluronic acid–methacrylate (HAMA) and gelatin–methacrylate (GelMA) microspheres for cartilage regeneration. The resulting 3D microenvironments supported homogeneous cell distribution, viability (>90%), and chondrogenic differentiation over 21 days. The microgels exhibited controlled diameters (250–500 μm), tunable stiffness (1–8 kPa), and stable mechanical integrity during culture. The study demonstrated that substrate elasticity and biochemical cues synergistically promoted the expression of SOX9, COL2A1, and ACAN, establishing these microspheres as scalable, reproducible building blocks for regenerative cartilage therapies.

Mechanical characterization of individual hydrogel microspheres was performed using a CellScale MicroSquisher to quantify microscale compressive modulus. Each hydrated microgel was placed between parallel plates and compressed at 10 μm/s to 40% strain at 37 °C in PBS. The MicroSquisher recorded force–displacement data, and Hertzian contact mechanics were used to calculate Young’s modulus (1–8 kPa depending on formulation). HAMA–GelMA hybrid gels demonstrated intermediate stiffness with improved viscoelastic recovery. These precise measurements validated matrix mechanical tunability and ensured microenvironment stiffness matched native cartilage tissue.

AUTHORS

Fabien Nativela, Audrey Smitha, Jeremy Boulestreaua, Charles Lepinec, Julie Baronc, Melanie Marquisd, Caroline Vignesa, Yoan Le Guenneca, Joelle Veziersa, Julie Lesoeura, François Lolla, Boris Halganda, Denis Renardd, Jerome Abadiee, Benoit Legoffa, Frederic Blancharda, Olivier Gauthiera, Claire Vinatiera, Anne des Rieuxb, Jerome Guicheuxa, Catherine Le Visage.

PUBLICATION DETAILS

JOURNAL

Biomaterials Advances

YEAR

2023

INSTITUTIONS

Université de Nantes, ONIRIS, CHU Nantes, INSERM, UCLouvain, INRAE

COUNTRIES

Belgium, France

INSTRUMENT USED

MicroSquisher

TESTING METHODS

Compression TestingHydrated and Temperature Controlled TestingMicro-Mechanical Testing

RESEARCH APPLICATIONS

Cartilage and Meniscus MechanicsCell Laden HydrogelsHydrogel Mechanical TestingInjectable & Regenerative BiomaterialsStem Cell Mechanobiology

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