Regulating Chondro‐Bone Metabolism for Treatment of Osteoarthritis via High‐Permeability Micro/Nano Hydrogel Microspheres

Abstract

Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro‐bone metabolic homeostasis is the key to the treatment of OA. However, traditional intra‐articular injections for the treatment of OA cannot directly break through the cartilage barrier to reach SB. In this study, the hydrothermal method is used to synthesize ultra‐small size (≈5 nm) selenium‐doped carbon quantum dots (Se‐CQDs, SC), which conjugated with triphenylphosphine (TPP) to create TPP‐Se‐CQDs (SCT). Further, SCT is dynamically complexed with hyaluronic acid modified with aldehyde and methacrylic anhydride (AHAMA) to construct highly permeable micro/nano hydrogel microspheres (SCT@AHAMA) for restoring chondro‐bone metabolic homeostasis. In vitro experiments confirmed that the selenium atoms scavenged reactive oxygen species (ROS) from the mitochondria of mononuclear macrophages, inhibited osteoclast differentiation and function, and suppressed early chondrocyte apoptosis to maintain a balance between cartilage matrix synthesis and catabolism. In vivo experiments further demonstrated that the delivery system inhibited osteoclastogenesis and H‐vessel invasion, thereby regulating the initiation and process of abnormal bone remodeling and inhibiting cartilage degeneration in SB. In conclusion, the micro/nano hydrogel microspheres based on ultra‐small quantum dots facilitate the efficient penetration of articular SB and regulate chondro‐bone metabolism for OA treatment.

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration

“…Fundamentally, this platform provides an excellent approach for inhibiting pyroptosis in IVDD therapy, likely through the inhibition of the IL-17/ERK signaling pathway. Although several nanohydrogel platforms for scavenging ROS, suppressing pyroptosis, and reducing ECM degeneration have been reported [ 59 , 65 ], the hydrogel platform developed in the present study can be released on demand, efficiently utilizes NPs, and acts multilaterally. Overall, TMP@Alg-PBA/PVA has therapeutic potential for the treatment of IVDD and warrants further systematic preclinical studies.…”

Applications of Hydrogels in Osteoarthritis Treatment

“…Xiao et al incorporated chemokines, macrophage antibodies, and engineered cell membrane vesicles (sEVs) into HAMA hydrogel microspheres, achieving precise macrophage reprogramming and regulation [130,131]. Zuo et al synthesized highly permeable nanogel microspheres using triphenylphosphine (TPP) and HAMA, enhancing cartilage and subchondral bone metabolism via ROS scavenging [132]. Li et al developed liposome-anchored teriparatide (PTH (1-34)) encapsulated in GelMA hydrogel microspheres, mitigating IL-1β-induced inflammation in ATDC5 cells by modulating the PI3K/AKT signaling pathway [133].…”

Transforming Osteoarthritis Treatment: Embracing Hydrogel Microspheres

“…Therefore, microspheres ranging from 100 to 300 μm are more commonly employed in OA treatment, and the selection of more accurate size options should be determined by animal species and models. 38,104,155 Next, microspheres with high porosity possess a larger specific surface area, facilitating enhanced drug storage and controlled slow release. 156 Furthermore, the pore structure also plays a crucial role in influencing cellular growth and differentiation within these microspheres, which is imperative for applications in regenerative medicine.…”

“…While the smallest microspheres prepared using the previously described method were 1 μm in size, excessively small microspheres would impede cell adhesion and be rapidly cleared; , larger microspheres are advantageous for sustained drug release but necessitate the use of wider-diameter needles, which may potentially damage the articular cartilage. Therefore, microspheres ranging from 100 to 300 μm are more commonly employed in OA treatment, and the selection of more accurate size options should be determined by animal species and models. ,, Next, microspheres with high porosity possess a larger specific surface area, facilitating enhanced drug storage and controlled slow release . Furthermore, the pore structure also plays a crucial role in influencing cellular growth and differentiation within these microspheres, which is imperative for applications in regenerative medicine. , Then, the friction coefficient of the microspheres also has an impact on the treatment outcome.…”