Motion lubrication suppressed mechanical activation via hydrated fibrous gene patch for tendon healing.

Mechanical activation of fibroblasts, caused by friction and transforming growth factor-ß1 recognition, is one of the main causes of tissue adhesions. In this study, we developed a lubricated gene-hydrogel patch, which provides both a motion lubrication microenvironment and gene therapy. The patch's outer layer is composed of polyethylene glycol polyester hydrogel. The hydrogel forms hydrogen bonds with water molecules to create the motion lubrication layer, and it also serves as a gene delivery library for long-term gene silencing. Under the motion lubricated microenvironment, extracellular signal-regulated kinase-small interfering RNA can silence fibroblasts and enhance the blocking effect against fibroblast activation. In vitro, the proposed patch effectively inhibits fibroblast activation and reduces the coefficient of friction. In vivo, this patch reduces the expression of vimentin and α-smooth muscle actin in fibroblasts. Therefore, the lubricated gene-hydrogel patch can inhibit the mechanical activation of fibroblasts to promote tendon healing.

Regulated Exogenous/Endogenous Inflammation via "Inner-Outer" Medicated Electrospun Fibers for Promoting Tissue Reconstruction.

Regenerative medicine aims to provide solutions for structural and functional recovery in conditions where organs suffer from varying degrees of diseases or injuries. However, the exogenous inflammation triggered by implanted biomaterials and endogenous inflammation caused by some disease or tissue destruction has not been solved properly yet. Herein, a functional "inner-outer" medicated core-shell electrospun fibrous membrane is fabricated with RGD surface modification for exogenous inflammation suppression and puerarin loading in the core for long-term endogenous inflammation inhibition through microsol electrospinning technique. The "outer" RGD significantly increases biocompatibility of fibrous membrane through promoting cell viability, adhesion, and proliferation while the "inner" puerarin suppresses inflammatory gene expression via sustained drug release in vitro. Moreover, in a rat abdominal wall hernia model, the functional fibrous membrane successfully reduces exogenous and endogenous inflammation response and promotes wound healing through collagen deposition, smooth muscle formation, and vascularization. In summary, the functional "inner-outer" medicated fibrous membrane holds a great potential for clinical treatment of diseases that needs tissue reconstruction structurally and functionally accompanied by immunoregulation.

A pH-Responsive Cluster Metal-Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect.

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, metal-organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap-ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.