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bioRxiv · 10.1101/2025.07.28.667232

A sulfonated cartilage interpenetrating polymer network reinforces and protects the extracellular matrix of degraded cartilage

DeMoya, C.·Husted, P.·Mehrota, D.·Albro, M.·Snyder, B.·Grinstaff, M.
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Abstract

Cartilage extracellular matrix (ECM) comprises a type-II collagen fibril network that affords structure and tensile strength, complemented by a negatively charged, sulfated glycosaminoglycan (GAG) matrix that retains interstitial water. These components act synergistically, bestowing the rheological and tribological material properties essential to cartilage function. At the onset of osteoarthritis, a disease characterized by cartilage degeneration, GAGs diminish from the ECM reducing interstitial fluid load support (IFLS) and transferring load to the collagen fibril network, which subsequently breaks down, culminating in increased hydraulic permeability, and decreased cartilage stiffness. We restore the material properties of damaged cartilage critical to diarthrodial joint function by forming an interpenetrating polymer network (IPN) with the native collagen using a synthetic, hydrophilic, and biocompatible GAG-mimetic polymer. Upon visible light activation, the monomer, 3-sulfopropylmethacrylate (SPM), and the crosslinker, polyethylene glycol diacrylate (PEGDA), form a sulfonated and anionic IPN that entangles and fills the existing porous degraded collagen matrix. Mechanistically, the highly sulfated, anionic SPM IPN retards water transport, reestablishes collagen fibril network integrity, and restores tissue IFLS, thereby returning the stiffness and viscoelastic properties of degraded cartilage to healthy levels. Additionally, the SPM IPN protects cartilage from further degradation by reducing the infiltration of inflammatory cytokines that upregulate catabolic matrix metalloproteinases and downregulate GAG production. Statement of significanceAmelioration of OA requires a comprehensive approach: neutralize or impede catabolic enzymes that degrade cartilage and reconstitute damaged cartilage by augmenting tissue ECM constituents. Currently, there are no clinical treatments that restore the viscoelastic material properties of hyaline cartilage tissue critical to its mechanical function and impart chondroprotection after OA induction. This work suggests that reconstituting GAG-depleted cartilage using a synthetic sulfonated interpenetrating polymer to reestablish IFLS that can be instilled into the joint and polymerized with white light during conventional arthroscopy represents a novel, minimally invasive, clinical treatment for early OA.

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DeMoya, C., Husted, P., Mehrota, D., Albro, M., Snyder, B., Grinstaff, M.. 2025-07-31. A sulfonated cartilage interpenetrating polymer network reinforces and protects the extracellular matrix of degraded cartilage. https://doi.org/10.1101/2025.07.28.667232

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