High-Density Horizontal Stacking of Chondrocytes via the Synergy of Biocompatible Magnetic Gelatin Nanocarriers and Internal Magnetic Navigation for Enhancing Cartilage Repair

Abstract

Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells. Here, we aimed to explore the repair effect of magnetized chondrocytes using magnetic amphiphilic-gelatin nanocarrier (MAGNC) to enhance cellular anchored efficiency and cellular magnetic guidance (MG) toward the superficial zone of damaged cartilage. The results of in vitro experiments showed that magnetized chondrocytes could be rapidly guided along the magnetic force line to form cellular amassment. Furthermore, the Arg-Gly-Asp (RGD) motif of gelatin in MAGNC could integrate the interaction among cells to form cellular stacking. In addition, MAGNCs upregulated the gene expression of collagen II (Col II), aggrecan, and downregulated that of collagen I (Col I) to reduce cell dedifferentiation. In animal models, the magnetized chondrocytes can be guided into the superficial zone with the interaction between the internal magnetic field and MAGNC to form cellular stacking. In vivo results showed that the intensity of N-sulfated-glycosaminoglycans (sGAG) and Col II in the group of magnetized cells with magnetic guiding was higher than that in the other groups. Furthermore, smooth closure of OA cartilage defects was observed in the superficial zone after 8 weeks of implantation. The study revealed the significant potential of MAGNC in promoting the high-density stacking of chondrocytes into the cartilage surface and retaining the biological functions of implanted chondrocytes for OA cartilage repair.

The Treatment of Keloid Scars via Modulating Heterogeneous Gelatin-Structured Composite Microneedles to Control Transdermal Dual-Drug Release

“…The amphiphilic gelatin (AG) was synthesized and purified using a previously described preparation process [ 26 ]. Briefly, gelatin powder (3 g) was dissolved in 40 mL deionised water, and 1 mL of 1 N NaOH was added to the gelatin solution while stirring at 70 °C overnight.…”

“…The QAGNs were prepared using the double emulsion method (W/O/W) in accordance with a previously described protocol, with minor modifications [ 26 ]. Briefly, AG (0.1 g) was dissolved in 4 mL of 0.05 N NaOH at 70 °C, and Qu was added at concentrations of 0.5 mg/mL, 1 mg/mL, 1.5 mg/mL, and 2 mg/mL.…”

Stimuli-responsive microcarriers and their application in tissue repair: A review of magnetic and electroactive microcarrier

“…These components are usually paramagnetic magnetic nanoparticles, which are small in size. They can specifically recognize the cell membrane [ 28 ] or be endocytosed by cells, and thereby affecting the behavior of cells [ 29 , 30 ].…”

“…Most integrins on the cell membrane will identify RGD sequences when conveying information, and antibodies are natural molecular markers that can specifically recognize antigens [ 77 , 188 ]. For example, Yang et al [ 29 ] modified RGDs on magnetized chondrocytes to create a high-density accumulation on the surface of cartilage. This concept was also applied by Woo et al [ 28 ] to obtain shear-reversible aggregates of alginate microspheres and chondrocytes, which demonstrated good in vivo biocompatibility.…”

A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM

“…These materials can respond to various triggers, such as temperature, enzymes, light, and magnetism [ [35] , [36] , [37] ]. Gelatin, a degradable natural protein, contains RGD sequences that promote cell adhesion and growth, has excellent biocompatibility and has been extensively used in tissue engineering [ 38 ]. Recent studies indicate that gelatin can degrade more rapidly in the presence of high Mmps levels, thus accelerating the release of encapsulated drugs [ 39 ].…”