Development of a stem cell-loaded NIR-responsive hydrogel system co-loaded with Kartogenin and manganese dioxide nanoparticles for image-guided, targeted regeneration of cartilage
Implementing Organization
Indian Institute Of Technology Madras
Principal Investigator
Dr. Sunil Venkanna Pogu
Indian Institute Of Technology Madras
sunilpogu@gmail.com
Project Overview
Osteoarthritis (OA) is the most prevalent form of arthritis, marked by progressive articular cartilage degradation and synovial inflammation, causing joint pain, stiffness, and functional disability. The primary reason for the OA is the imbalance in the ratio of catabolism and anabolism maintained by the chondrocytes in the Extracellular Matrix (ECM) of cartilage. In 2019, approximately 62.2 million Indian individuals were affected by OA, which is more than 120% compared to cases in 1990 (approx. 23.2 million), indicating the urgent need to establish safe and efficient therapy for mitigating OA. While several studies have advanced the therapeutic modalities for OA, most are limited by a single therapeutic focus and lack integrated functionality. For example, CuS nanoparticles with TGF-β1 plasmids enhanced MSC chondrogenesis but lacked scaffolding, imaging, biodegradability and ROS modulation. The pH-responsive liposome–Kartogenin–GelMA system enabled localised drug release but excluded stem cells and diagnostic capability. The Pluronic F127/HA–MSC hydrogel, effective in uterine repair, lacked OA-specific cues like kartogenin and had no imaging or environmental responsiveness. Collectively, these approaches fail to combine biodegradability, regeneration, and real-time monitoring in a single platform.
Therefore, the current research proposes a multifunctional hydrogel containing MnO2 nanoparticles (NP)-loaded with NIR Dye (Indocyanine Green), Kartogenin, and mesenchymal stem cells. This multifunctional hydrogel combines key components for effective osteoarthritis therapy. Gelatin, a natural biopolymer, mimics the ECM, providing a suitable environment for MSCs growth and differentiation, while Pluronic F127, a thermosensitive tri-block polymer, is in liquid form at lower temperatures and forms a stable gel at body temperature, providing injectability and stability at the joint. MnO₂ biodegradable nanoparticles scavenge ROS, enhance MRI contrast essential in clinical bioimaging, and stimulate MSC chondrogenic differentiation. Further, MnO₂ enhances the loading and targetability of therapeutic moieties. Indocyanine Green is an NIR dye for NIR imaging and controlled photothermal drug release. Kartogenin promotes MSC differentiation toward cartilage formation by activating the CBFβ–RUNX1 signalling pathway. MSCs serve as living therapeutics, under suitable conditions provided by the hydrogel containing MnO₂ and kartogenin will differentiate into chondrocytes and synthesise essential components needed for cartilage synthesis and repair. The synthesised hydrogel will be used to evaluate the in vitro biocompatibility, stem cells growth and differentiation, and chondrogenesis. Further, an in vivo OA rat model will be developed to determine the theranostic outcome of the hydrogel. The proposed system represents a minimally invasive, image-guided, and bioactive therapeutic platform designed to facilitate cartilage regeneration and repair in OA.