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Injectable cell-based hydrogels allow surgical operation in a minimally invasive way for articular cartilage lesions but the chondrocytes in the injectable hydrogels are difficultly arrayed and fixed at the site of interest to repair the cartilage tissue. In this study, an injectable hyaluronic acid–polyacrylic acid (HA–pAA) hydrogel was first synthesized using hyaluronic acid–cyclodextrin (HA–CD) and polyacrylic acid–ferrocene (pAA–Fc) to provide cell-delivery and self-healing. To promote the cell fixation and alignment, porous poly(lactic-co-glycolic acid) (PLGA) magnetic microcapsules (PPMMs) with glutathione (GSH) loaded and iron oxide nanoparticles (IO) located in the shell were designed. The GSH-loaded PPMMs with layer-by-layer (LbL) assembly of hyaluronic acid (HA) and GSH (LbL-PPMMs) can provide a two-stage rapid and slow release of GSH to modulate the self-healing of the HA–pAA hydrogel at the injured site. Furthermore, the chondrocytes embedded in the HA–pAA hydrogel could be delivered through CD44 receptors on the HA polymer chains of LbL-PPMMs toward the surface of the damaged site by an internal magnetic force. The composite hydrogel system of chondrocytes/LbL-PPMMs/HA–pAA can provide the damaged cartilage with a more even and smooth surface than other groups in a rabbit model after 8 weeks of implantation. In addition, the chondrocytes in the deep zone tissue exhibit a columnar array, similar to the cell arrangement in normal cartilage tissue. Together with the cell navigation behavior and GSH release from the LbL-PPMM/HA–pAA hydrogel, a full closure of lesions on the cartilage tissue can be achieved. Our results demonstrate the highly promising potential of the injectable LbL-PPMM/HA–pAA system in cartilage tissue repair.

Serious side effects from chemotherapies are the main problem with cancer treatments. To solve these issues, precision cancer nanomedicine based on natural therapeutic materials is developed, which enables specifically apoptosis by interacting with genetic mutation in cancer cells, while leaving normal cells unaffected. Here, we report a novel nanomedicine (CuQDA/IO@HA) composed of hyaluronic acid (HA) / copper ion (Cu(II))-chelated dextran-aldehyde (DA)-quercetin (Q) with dual targeting for synthetic lethal therapy. The CuQDA/IO@HA prepared using a ratio of metal/Q at 0.5:1 resulted in a stable particle structure with uniform particle distribution. The CuQDA/IO@HA can specifically target and induce specific cytotoxicity in BRCA-mutant cancer cells in vitro. Combination treatment with CuQDA/IO@HA and magnetic navigation can induce poly (ADP-ribose) polymerase (PARP) inhibition and DNA damage in BRCA-mutant triple-negative breast cancer (TNBC) via CD44 targeting. The dual-targeting CuQDA/IO@HA can extend the median survival of the BRCA-mutant xenograft mice from 34 to 61 days in comparison to Q treatment alone in vivo, which is attributed to the significant increase in γH2AX, leading to significant apoptosis. More importantly, the CuQDA/IO@HA displayed biocompatibility and no obvious side-effect in normal organs. These results demonstrate the promising potential of integrating natural and metal ions into a nanomedicine that can provide precision medicine through synthetic lethality.

The articular cartilage disorder at the junction mainly results from constantly repeated dynamic tension/compression effects with ageing and lack of intrinsic defect repairability. Therefore, the degradable piezoelectric scaffolds are very essential, which mimics the dynamic mechanical loading and optimizes the chondrocyte differentiation during the degradation. Here, a degradable aligned electrospun poly- L -lactic acid (PLLA) modified with graphene (rGO) and polydopamine (PDA) fibrous scaffolds with different orientations (0°, 90°) and surface morphologies (wrinkled and porous) was developed as a biocompatible and degradable piezoelectric scaffold with the self-powered tunable piezoelectricity to modulate cell behaviour and cell differentiation by tuning the degradation effect. The results show that the electrical output and mechanical properties of the composite fibrous scaffold can be improved by adding rGO and applying mechanical force along with the 90° orientation. With changing the degradation behavior, dynamic mechanical loading on the porous PLLA/rGO/PDA fibrous scaffold exhibits a significant increase in cell proliferation and secretion of extracellular matrix (ECM). More surprisingly, as extending the degradation periods to 21 days, a higher glycosaminoglycans (GAGs) synthesis was detected in prechondrogenic ATDC5 cells cultured on the degraded porous scaffold compared with that after 7 days’ culture. This indicated that long-term degradation favoured promoting cell differentiation of ATDC5 towards a chondrogenic phenotype due to dynamic mechanical loading, low-intensity electrical stimulation, and interconnected porous structural morphology. In contrast, on the wrinkled PLLA/rGO/PDA fibre with a high-intensity electrical stimulation, the ALP activity significantly increased after 21 days, inducing mineralization with the differentiation of ATDC5 into osteocytes. The modulation of the degraded environment and electrical stimulation of the piezoelectric scaffold offers an effective alternative to influence cell functions, significantly improving the ECM secretion and cell differentiation.