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Ultra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration.

ABSTRACT: Osteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent drug release behavior. We demonstrate that the hydrogel can withstand 28000 loading-unloading mechanical cycles and exhibits fast shape memory at body temperature (30 s) with the potential for minimally invasive surgery. We find that the hydrogel can also alleviate the inflammatory reaction and regulate oxidative stress in situ to establish a microenvironment conducive to healing. We show that the sequential release of tannic acid and Kartogenin can promote the migration of bone marrow mesenchymal stem cells into the hydrogel scaffold, followed by the induction of chondrocyte differentiation, thus leading to full-thickness cartilage regeneration in vivo. This work may provide a promising solution to address the problem of cartilage regeneration.

SUBMITTER: Yang Y

PROVIDER: S-EPMC10682016 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Ultra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration.

Yang Yuxuan Y Zhao Xiaodan X Wang Shuang S Zhang Yanfeng Y Yang Aiming A Cheng Yilong Y Chen Xuesi X

Nature communications 20231127 1

Osteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent ...[more]

PMID: 38012159

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Project description:BackgroundDespite intensive research, regeneration of articular cartilage largely remains an unresolved medical concern as the clinically available modalities still suffer from long-term inconsistent data, relatively high failure rates and high prices of more promising approaches, such as cell therapy. In the present study, we aimed to evaluate the feasibility and long-term efficacy of a bilayered injectable acellular affinity-binding alginate hydrogel in a large animal model of osteochondral defects.MethodsThe affinity-binding alginate hydrogel is designed for presentation and slow release of chondrogenic and osteogenic inducers (transforming growth factor-β1 and bone morphogenic protein 4, respectively) in two distinct and separate hydrogel layers. The hydrogel was injected into the osteochondral defects created in the femoral medial condyle in mini-pigs, and various outcomes were evaluated after 6 months.ResultsMacroscopical and histological assessment of the defects treated with growth factor affinity-bound hydrogel showed effective reconstruction of articular cartilage layer, with major features of hyaline tissue, such as a glossy surface and cellular organisation, associated with marked deposition of proteoglycans and type II collagen. Microcomputed tomography showed incomplete bone formation in both treatment groups, which was nevertheless augmented by the presence of affinity-bound growth factors. Importantly, the physical nature of the applied hydrogel ensured its shear resistance, seamless integration and topographical matching to the surroundings and opposing articulating surface.ConclusionsThe treatment with acellular injectable growth factor-loaded affinity-binding alginate hydrogel resulted in effective tissue restoration with major hallmarks of hyaline cartilage, shown in large animal model after 6-month follow-up.The translational potential of this articleThis proof-of-concept study in a clinically relevant large animal model showed promising potential of an injectable acellular growth factor-loaded affinity-binding alginate hydrogel for effective repair and regeneration of articular hyaline cartilage, representing a strong candidate for future clinical development.

Dataset Information

Ultra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration.

Publications

Ultra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration.

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