Dataset Information

Structure-Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation.

ABSTRACT: Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n?=?27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (>?0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension.

SUBMITTER: Ebrahimi M

PROVIDER: S-EPMC7723942 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Structure-Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation.

Ebrahimi Mohammadhossein M Turunen Mikael J MJ Finnilä Mikko A MA Joukainen Antti A Kröger Heikki H Saarakkala Simo S Korhonen Rami K RK Tanska Petri P

Annals of biomedical engineering 20200709 12

Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content ...[more]

PMID: 32648191

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Project description:Understanding intra-articular biodistribution is imperative as candidate osteoarthritis (OA) drugs become increasingly site-specific. Cartilage has been identified as opportunistic for therapeutic intervention, but poses numerous barriers to drug delivery. To facilitate drug delivery to cartilage, nanoscale vehicles have been designed with different features that target the tissue's matrix. However, it is unclear if these targeting strategies are influenced by OA and the associated structural changes that occur in cartilage. The goal of this work was to study the effectiveness of different cartilage-targeting nanomaterials with respect to cartilage localization and retention, and to determine how these outcomes change in OA. To address these questions, a nanoparticle (NP) system was developed, and the formulation was tuned to possess three distinct cartilage-targeting strategies: (1) passive targeting cationic NPs for electrostatic attraction to cartilage, (2) active targeting NPs with binding peptides for collagen type II, and (3) untargeted neutrally-charged NPs. Ex vivo analyses with bovine cartilage explants demonstrated that targeting strategies significantly improved NP associations with both healthy and OA-like cartilage. In vivo studies with collagenase-induced OA in rats revealed that disease state influenced joint biodistribution for all three NP formulations. Importantly, the extent of cartilage accumulation for each NP system was affected by disease differently; with active NPs, but not passive NPs, cartilage accumulation was increased in OA relative to healthy knees. Together, this work suggests that NPs can be strategically designed for site-specific OA drug delivery, but the biodistribution of the NPs are influenced by the disease conditions into which they are delivered. STATEMENT OF SIGNIFICANCE: As emerging drugs for osteoarthritis are becoming increasingly site-specific, the need for targeted intra-articular drug delivery has evolved. To improve drug delivery to cartilage, targeting strategies for nanomaterials have been developed, but the manner in which these targeted systems accumulate at different sites within the joint remains poorly understood. Moreover, it is unclear how nanomaterial-tissue interactions change in osteoarthritic conditions, as tissue structure and composition change after disease onset. By understanding how nanomaterials distribute within healthy and disease joints, we can advance targeted drug delivery strategies and improve therapeutic outcomes for emerging drugs.

Dataset Information

Structure-Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation.

Publications

Structure-Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation.

Similar Datasets

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