Mechanically graded granular scaffolds for osteochondral tissue engineering
Year: 2026
Type: article
Abstract: Engineered scaffolds designed to approximate the mechanical microenvironment of the osteochondral unit often address this complexity using discrete, two-phase architectures that introduce mechanical discontinuities and interfacial stress concentrations rather than a contiguous stiffness transition. To address this challenge, we created a photoannealed polyethylene glycol (PEG) granular scaffold with a spatially controlled stiffness gradient within a cell-permissive, macroporous architecture. Stiffness was dictated by photoannealing microgels using a photomask. We tuned void volume and available surface area by varying microgel diameter and tested how mesenchymal stromal cells (MSCs) interpret local mechanical environments. MSCs exhibited position-dependent differences in morphology, cytoskeletal structure, matrix deposition, and lineage-specific gene expression within the gradient scaffolds. Softer regions supported rounded cell morphology and deposition of a glycosaminoglycan-rich matrix, whereas stiffer regions promoted cell elongation, increased cytoskeletal tension, and expression of mineral-associated markers. Gradients formed from smaller microgels magnified these spatial responses by increasing cellular confinement and adhesion site availability. Disruption of actomyosin contractility eliminated these regional differences, demonstrating that MSCs rely on tension-dependent mechanotransduction to interpret the gradient. These findings reveal that coupling microgel architecture with continuous stiffness transitions provides a tractable platform to study multiscale mechanobiologic regulation and spatially guide osteochondral tissue formation.
Source: Biomaterials Advances
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
Funders: Foundation for the National Institutes of Health, U.S. Department of Energy, National Institutes of Health, Office of the President, University of California, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, Lawrence Livermore National Laboratory
Awards: G1356433355, G29567018, G5753692810, Dual peptide presentation from bioengineered carriers to potentiate stromal cell function and tissue repair, Identifying the superior ossification pathway for tissue engineered approaches to long bone repair, MUSCLE: MUsculoSkeletal Clinical Learning Experience Transdisciplinary Musculoskeletal Research Training Program
OpenAlex ID: W7160186546