Intelligent GelMA microspheres co-loaded with BMSCs and Kartogenin for spatiotemporally controlled release and immunomodulatory regeneration of temporomandibular joint osteoarthritis.

Authors

Feng Feng, Bin Xing, Wen Liu

Published in

Frontiers in immunology. Volume 17. Pages 1921455. Epub Sep 16, 2026.

Abstract

This study aims to overcome the limitations of current treatments for temporomandibular joint osteoarthritis (TMJOA), which often fail to promote cartilage regeneration and necessitate repeated administrations. To this end, an injectable intelligent GelMA microsphere platform co-loaded with bone marrow mesenchymal stem cells (BMSCs) and the small molecule Kartogenin (KGN) was developed. This system facilitates spatiotemporally controlled release and immunomodulatory regeneration within the joint cavity. The therapeutic efficacy and underlying mechanisms of this approach for TMJOA were systematically evaluated.
GelMA porous microspheres loaded with BMSCs and KGN were fabricated utilizing microfluidic technology. The physicochemical characteristics of the microspheres and the in vitro release profile of KGN were assessed through scanning electron microscopy, swelling assays, degradation studies, and high-performance liquid chromatography. In vitro biocompatibility was evaluated by co-culturing the microspheres with rabbit chondrocytes, followed by analysis of the expression of genes and proteins associated with chondrogenic differentiation. The anti-inflammatory effects were investigated via macrophage polarization assays. In vivo, a rabbit TMJOA model was established using sodium iodoacetate and subsequently divided into control, OA, GelMA@KGN microsphere, and GelMA@KGN-BMSC microsphere groups. Histological staining, immunohistochemistry, immunofluorescence, and qRT-PCR analyses of the condylar tissue were conducted at 4 and 8 weeks post-treatment.
The prepared GelMA@KGN-BMSC microspheres demonstrated uniform particle size, interconnected porosity, favorable swelling behavior, and characteristic degradation profiles, with KGN exhibiting a sustained release pattern. In vitro studies revealed a high viability of chondrocytes, with cells exhibiting extensive spreading on the microsphere surfaces. In the GelMA@KGN-BMSC group, chondrocytes showed significantly elevated expression levels of chondrogenic-related genes and proteins, alongside a marked reduction in the expression of matrix-degrading enzymes. Macrophage polarization assays indicated that these microspheres substantially promoted M2 polarization while inhibiting M1 polarization. In vivo assessments revealed that treatment with the GelMA@KGN-BMSC microspheres preserved cartilage structure integrity, significantly enhanced cartilage matrix synthesis and reduced inflammatory factor expression. These therapeutic effects were notably superior to those observed in the GelMA@KGN microsphere group.
The GelMA@KGN-BMSC intelligent microsphere system developed in this study enables localized delivery of BMSCs and sustained release of KGN through a single intra-articular injection. These GelMA@KGN-BMSC microspheres significantly enhance cartilage regeneration via a synergistic mechanism that integrates induced differentiation and immunomodulation, offering a safe and effective minimally invasive therapeutic approach for TMJOA.

PMID:
42819405
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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