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Mechanically graded granular scaffolds for osteochondral tissue engineering.

Sabrina C Mierswa1, Erika E Wheeler2, Monica L Moya3

  • 1Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, 95817, USA; Department of Biomedical Engineering, University of California, Davis, CA, 95616, USA; Engineering Directorate, Lawrence Livermore National Laboratory, Livermore, CA, USA.

Biomaterials Advances
|May 3, 2026
PubMed
Summary

Engineered scaffolds with continuous stiffness gradients guide mesenchymal stromal cells (MSCs) for osteochondral tissue regeneration. These advanced biomaterials mimic the natural tissue microenvironment, improving cell behavior and matrix deposition.

Keywords:
GradientMicrogelsOsteochondralPhotocrosslinkingStiffness

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Area of Science:

  • Biomaterials Engineering
  • Tissue Engineering
  • Mechanobiology

Background:

  • Osteochondral unit regeneration is challenging due to complex mechanical microenvironments.
  • Existing scaffolds often create mechanical discontinuities, unlike native tissue.
  • Continuous stiffness transitions are needed for better biomimicry.

Purpose of the Study:

  • To develop a photoannealed polyethylene glycol (PEG) scaffold with a spatially controlled stiffness gradient.
  • To investigate how mesenchymal stromal cells (MSCs) respond to these engineered mechanical gradients.
  • To explore the potential of these scaffolds for guiding osteochondral tissue formation.

Main Methods:

  • Fabrication of PEG granular scaffolds with stiffness gradients via photoannealing microgels with photomasks.
  • Tuning scaffold properties like void volume and surface area by varying microgel diameter.
  • Culturing MSCs within the gradient scaffolds and analyzing cell morphology, cytoskeleton, matrix deposition, and gene expression.
  • Investigating the role of actomyosin contractility in MSC mechanotransduction.

Main Results:

  • MSCs exhibited position-dependent morphology, cytoskeletal organization, and matrix deposition.
  • Softer regions promoted glycosaminoglycan-rich matrix, while stiffer regions enhanced cell elongation and mineral-associated gene expression.
  • Smaller microgel-derived gradients amplified MSC spatial responses.
  • Disruption of actomyosin contractility abolished regional MSC differences, confirming tension-dependent mechanotransduction.

Conclusions:

  • Continuous stiffness gradients in PEG scaffolds effectively guide MSC behavior and tissue formation.
  • This platform allows for studying multiscale mechanobiologic regulation in a biomimetic manner.
  • The developed scaffolds offer a promising approach for spatially directing osteochondral tissue engineering.