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Injectable, Reactive Oxygen Species-Responsive Collagen Hydrogel for Peptide-Directed and On-Demand Nanotherapy of
Xiaoyan Wang1,2, Xian Chen1,2, Lili Wang1,2
1State Key Laboratory of Natural Product Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China.
Abstract:
Osteoarthritis (OA) is a degenerative joint disease characterized by chronic inflammation and cartilage loss. However, disease-modifying treatments are still unavailable, and even promising nanomaterials are hindered by rapid clearance and poor targeting. Herein, we reported a peptide-modified and reactive oxygen species (ROS) responsive collagen hydrogel (CSH-AuNCs-CIITP) that coupled environmental adaptability with molecular precision for spatiotemporally regulated cartilage regeneration. Gold nanoclusters were functionalized with a type II collagen-targeting peptide (CIITP) for cartilage affinity and encapsulated within a ROS-cleavable disulfide-crosslinked collagen hydrogel (CSH), yielding an injectable, self-healing system with enhanced mechanical integrity and enzymatic stability. The hydrogel achieves ROS-triggered, on-demand release of therapeutic nanoclusters within the OA microenvironment. In vitro, this hydrogel system promoted BMSCs chondrogenesis and macrophage M2 polarization. In vivo, it facilitated preliminary integration and repair with robust matrix restoration. This ROS-activated cartilage-targeting platform integrates nano-bio interactions, dynamic covalent chemistry, and microenvironmental modulation. It achieves precise cartilage targeting, prolonged intra-articular retention, and spatiotemporally regulated bioactivity, culminating in superior anti-inflammatory and chondroregenerative outcomes, offering a promising strategy for nanomaterial-enabled osteoarthritis therapy.
Insights
A novel hydrogel system targets osteoarthritis by releasing therapeutic gold nanoclusters in response to reactive oxygen species (ROS). This approach enhances cartilage regeneration and reduces inflammation, offering a new strategy for osteoarthritis therapy.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Nanotechnology
Background:
- Osteoarthritis (OA) is a degenerative joint disease with limited disease-modifying treatments.
- Current nanomaterial therapies for OA face challenges like rapid clearance and poor targeting.
- Effective treatments require strategies for precise delivery and controlled release within the OA joint environment.
Purpose of the Study:
- To develop a peptide-modified, ROS-responsive collagen hydrogel for targeted cartilage regeneration in OA.
- To create an injectable, self-healing hydrogel system with enhanced stability and controlled therapeutic release.
- To evaluate the in vitro and in vivo efficacy of this platform for OA treatment.
Main Methods:
- Fabrication of a collagen hydrogel (CSH) encapsulating gold nanoclusters (AuNCs) functionalized with a type II collagen-targeting peptide (CIITP).
- The hydrogel matrix was designed to be disulfide-crosslinked for ROS-cleavable degradation.
- In vitro studies assessed chondrogenesis of bone marrow-derived stem cells (BMSCs) and macrophage polarization. In vivo studies evaluated cartilage repair and integration.
Main Results:
- The CSH-AuNCs-CIITP hydrogel demonstrated injectability, self-healing properties, and enhanced mechanical/enzymatic stability.
- ROS triggered the on-demand release of CIITP-functionalized AuNCs within the OA microenvironment.
- In vitro, the system promoted BMSC chondrogenesis and M2 macrophage polarization. In vivo, it facilitated cartilage integration and matrix restoration.
Conclusions:
- The ROS-activated, cartilage-targeting hydrogel platform effectively integrates nanotechnology and biomaterial design for OA therapy.
- This system achieves precise targeting, prolonged retention, and spatiotemporally regulated bioactivity.
- The developed hydrogel offers a promising strategy for nanomaterial-enabled osteoarthritis treatment with superior anti-inflammatory and chondroregenerative outcomes.