Liver fibrosis, as one of the leading causes of liver‐related morbidity and mortality, has no Food and Drug Administration (FDA)‐approved antifibrotic therapy yet. Although microRNA‐29b (miRNA‐29b) and microRNA‐122 (miRNA‐122) have great potential in treating liver fibrosis via regulating profibrotic genes in hepatic stellate cells (HSCs), it is still a challenge to achieve a HSC‐targeted and meanwhile noninvasively trackable delivery of miRNAs in vivo. Herein, a pH‐sensitive and vitamin A (VA)‐conjugated copolymer VA–polyethylene glycol–polyethyleneimine–poly(N‐(N′,N′‐diisopropylaminoethyl)‐co‐benzylamino) aspartamide (T‐PBP) is synthesized and assembled into superparamagnetic iron oxide (SPIO)‐decorated cationic micelle for miRNA delivery. The T‐PBP micelle efficiently transports the miRNA‐29b and miRNA‐122 to HSC in a magnetic resonance imaging‐visible manner, resulting in a synergistic antifibrosis effect via downregulating the expression of fibrosis‐related genes, including collagen type I alpha 1, α‐smooth muscle actin, and tissue inhibitor of metalloproteinase 1. Consequently, the HSC‐targeted combination therapy with miRNA‐29b and miRNA‐122 demonstrates a prominent antifibrotic efficacy in terms of improving liver function and relieving hepatic fibrosis.

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.