Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes ( P16 ^INK4a /P21 ) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.

A biodegradable and self-electrified conduit device is achieved to offer postoperative electrical cues for nerve regeneration.

Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.

Complex hierarchical architectures are ubiquitous in natural hard tissues, which comprise an elaborate assembly of hard and soft phases spanning from the nanoscale to the macroscale. The elegant architectures grant unique performance in terms of strength and toughness, but the biomimetic fabrication of synthetic materials with highly consistent structural and mechanical characteristics with natural counterparts remains a great challenge. Here, a centimeter‐size artificial lamellar bone is successfully fabricated for the first time via a well‐orchestrated “multiscale cascade regulation” strategy combining multiple techniques of molecular self‐assembly, electrospinning, and pressure‐driven fusion from molecular to macroscopic levels. The bulk artificial lamellar bone that is composed of hierarchically assembled mineralized collagen fibrils with a waiver of any synthetic polymer highly resembles the chemical composition, multiscale structural organization, and rotated plywood‐like structure of natural lamellae, thus achieving a good combination of lightweight and high‐stiffness (E_y ≈ 15.2 GPa), ‐strength (σ_f ≈ 118.4 MPa), and ‐toughness (K_JC ≈ 9.3 MPa m^1/2). This multiscale cascade regulation strategy can break through the limitations of a single technique and enable the construction of elaborate composite materials with multiscale step‐by‐step regulations of hierarchically structural organizations for unique mechanical properties.