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Updated: Jul 17, 2026
Fabrication of Size-Controlled and Emulsion-Free Chitosan-Genipin Microgels for Tissue Engineering Applications
Published on: April 13, 2022
Injectable microgels carrying engineered biomimetic nanoparticles for osteoarthritis therapy via dual-targeted
Peng Wang1,2, Haiyue Zhao1,3, Shuo Zhang1,3
1Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
Abstract:
The accumulation of senescent chondrocytes contributes significantly to osteoarthritis (OA) progression, establishing a self-perpetuating cycle of cartilage deterioration. Current therapeutic strategies remain limited by inadequate precision to target senescent populations and the inability to simultaneously trigger endogenous regenerative processes. Herein, we developed a hydrogel microsphere system to locally eliminate senescent chondrocytes, thereby creating a permissive microenvironment and facilitating endogenous stem cell recruitment to accelerate cartilage repair. Specifically, chondrocyte membranes (CM) overexpressing natural killer group 2 member D (NKG2D) receptors (NCM) were fabricated via plasmid transfection and extrusion to target upregulated NKG2D ligands on senescent cells. The fusion of ABT263-loaded liposomes (A-lipo) with NCM produced the senolytic ANCM nanoparticles. Subsequently, ANCM and SDF-1α were co-encapsulated into methacrylic anhydride (MA)-modified hyaluronic acid (HA) hydrogel microspheres (SHM) using microfluidics. The resulting ANCM@SHM exhibited remarkable biocompatibility and a dual-phase functionality: hydrogel-enhanced articular retention followed by ANCM-mediated active targeting of senescent chondrocytes. Functional assessments validated the effective clearance of senescent chondrocytes, achieved by inducing mitochondrial outer membrane permeabilization (MOMP), was accompanied by metabolic reprogramming of surviving chondrocytes toward an anabolic phenotype. Simultaneously, sustained SDF-1α release induced robust mesenchymal stromal cells (MSCs) homing and chondrogenic differentiation, resulting in synergistic cartilage remodeling. In vivo evaluations demonstrated a pronounced attenuation of OA progression, attributable to synergistic remodeling of the joint microenvironment. This multidimensional engineering strategy disrupts the vicious cycle of senescence-associated cartilage degeneration by integrating targeted senolysis with stem cell-mediated regeneration, providing a promising therapeutic approach for OA management.
Insights
This study developed a novel hydrogel microsphere system to eliminate senescent chondrocytes, promoting cartilage repair by recruiting stem cells for osteoarthritis treatment.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Osteoarthritis Research
Background:
- Senescent chondrocytes drive osteoarthritis (OA) progression through a destructive cycle.
- Existing OA therapies lack precision and fail to stimulate endogenous repair.
Purpose of the Study:
- To engineer a targeted delivery system for senescent chondrocyte elimination and cartilage regeneration.
- To develop a dual-functional hydrogel microsphere system for OA management.
Main Methods:
- Fabrication of senolytic nanoparticles (ANCM) targeting senescent chondrocytes via NKG2D receptors.
- Co-encapsulation of ANCM and SDF-1α into hyaluronic acid hydrogel microspheres (SHM).
- In vitro and in vivo evaluation of ANCM@SHM for cartilage repair efficacy.
Main Results:
- ANCM@SHM effectively cleared senescent chondrocytes by inducing apoptosis.
- Treatment promoted chondrocyte anabolism and recruited mesenchymal stromal cells (MSCs).
- In vivo studies showed significant attenuation of OA progression and cartilage regeneration.
Conclusions:
- The engineered hydrogel microspheres offer a promising therapeutic strategy for OA.
- This approach integrates targeted senolysis with stem cell-mediated regeneration to disrupt cartilage degeneration.
- The system demonstrates potential for effective osteoarthritis management.
