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Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering.

ABSTRACT: Scaffolds with cartilage-like environment and suitable physical properties are critical for tissue-engineered cartilage repair. In this study, decellularized porcine cartilage-derived extracellular matrix (ECM) was utilized to fabricate ECM scaffolds. Mechanically reinforced ECM scaffolds were developed by combining salt-leaching and crosslinking for cartilage repair. The developed scaffolds were investigated with respect to their physicochemical properties and their cartilage tissue formation ability. The mechanically reinforced ECM scaffold showed similar mechanical strength to that of synthetic PLGA scaffold and expressed higher levels of cartilage-specific markers compared to those expressed by the ECM scaffold prepared by simple freeze-drying. These results demonstrated that the physical properties of ECM-derived scaffolds could be influenced by fabrication method, which provides suitable environments for the growth of chondrocytes. By extension, this study suggests a promising approach of natural biomaterials in cartilage tissue engineering.

SUBMITTER: Oh HJ

PROVIDER: S-EPMC6171674 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering.

Oh Hyun Ju HJ Kim Soon Hee SH Cho Jae-Ho JH Park Sang-Hyug SH Min Byoung-Hyun BH

Tissue engineering and regenerative medicine 20180208 3

Scaffolds with cartilage-like environment and suitable physical properties are critical for tissue-engineered cartilage repair. In this study, decellularized porcine cartilage-derived extracellular matrix (ECM) was utilized to fabricate ECM scaffolds. Mechanically reinforced ECM scaffolds were developed by combining salt-leaching and crosslinking for cartilage repair. The developed scaffolds were investigated with respect to their physicochemical properties and their cartilage tissue formation a ...[more]

PMID: 30603554

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Project description:Cartilage tissue engineering strategies often rely on hydrogels with fixed covalent crosslinks for chondrocyte encapsulation, yet the resulting material properties are largely elastic and can impede matrix deposition. To address this limitation, hydrazone crosslinked poly(ethylene glycol) hydrogels were formulated to achieve tunable viscoelastic properties and to study how chondrocyte proliferation and matrix deposition vary with the time-dependent material properties of covalent adaptable networks. Hydrazone equilibrium differences were leveraged to produce average stress relaxation times from hours (4.01 × 103 s) to months (2.78 × 106 s) by varying the percentage of alkyl-hydrazone (aHz) and benzyl-hydrazone (bHz) crosslinks. Swelling behavior and degradation associated with adaptability were characterized to quantify temporal network changes that can influence the behavior of encapsulated chondrocytes. After four weeks, mass swelling ratios varied from 36 ± 3 to 17 ± 0.4 and polymer retention ranged from 46 ± 4% to 92 ± 5%, with higher aHz content leading to loss of network connectivity with time. Hydrogels were formulated near the Flory-Stockmayer bHz percolation threshold (17% bHz) to investigate chondrocyte response to distinct levels of covalent architecture adaptability. Four weeks post-encapsulation, formulations with average relaxation times of 3 days (2.6 × 105s) revealed increased cellularity and an interconnected articular cartilage-specific matrix. Chondrocytes embedded in this adaptable formulation (22% bHz) deposited 190 ± 30% more collagen and 140 ± 20% more sulfated glycosaminoglycans compared to the 100% bHz control, which constrained matrix deposition to pericellular space. Collectively, these findings indicate that incorporating highly adaptable aHz crosslinks enhanced regenerative outcomes. However, connected networks containing more stable bHz bonds were required to achieve the highest quality neocartilaginous tissue. STATEMENT OF SIGNIFICANCE: Covalently crosslinked hydrogels provide robust mechanical support for cartilage tissue engineering applications in articulating joints. However, these materials traditionally demonstrate purely elastic responses to deformation despite the dynamic viscoelastic properties of native cartilage tissue. Here, we present hydrazone poly(ethylene glycol) hydrogels with tunable viscoelastic properties and study covalent adaptable networks for cartilage tissue engineering. Using hydrazone equilibrium and Flory-Stockmayer theory we identified average relaxation times leading to enhanced regenerative outcomes and showed that extracellular matrix deposition was biphasic as a function of the hydrazone covalent adaptability. We also showed that the incorporation of highly adaptable covalent crosslinks could improve cellularity of neotissue, but that a percolating network of more stable bonds was required to maintain scaffold integrity and form the highest quality neocartilaginous tissue.

Dataset Information

Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering.

Publications

Mechanically Reinforced Extracellular Matrix Scaffold for Application of Cartilage Tissue Engineering.

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