Single-Atom Cu Nanozyme-Loaded Bone Scaffolds for Ferroptosis-Synergized Mild Photothermal Therapy in Osteosarcoma Treatment.

The rapid multiplication of residual tumor cells and poor reconstruction quality of new bone are considered the major challenges in the postoperative treatment of osteosarcoma. It is a promising candidate for composite bone scaffold which combines photothermal therapy (PTT) and bone regeneration induction for the local treatment of osteosarcoma. However, it is inevitable to damage the normal tissues around the tumor due to the hyperthermia of PTT, while mild heat therapy shows a limited effect on antitumor treatment as the damage can be easily repaired by stress-induced heat shock proteins (HSP). This study reports a new type of single-atom Cu nanozyme-loaded bone scaffolds, which exhibit exceptional photothermal conversion properties as well as peroxidase and glutathione oxidase mimicking activities in vitro experiments. This leads to lipid peroxidation (LPO) and reactive oxygen species (ROS) upregulation, ultimately causing ferroptosis. The accumulation of LPO and ROS also contributes to HSP70 inactivation, maximizing PTT efficiency against tumors at an appropriate therapeutic temperature and minimizing the damage to surrounding normal tissues. Further, the bone scaffold promotes bone regeneration via a continuous release of bioactive ions (Ca2+, P5+, Si4+, and Cu2+). The results of in vivo experiments reveal that scaffolds inhibit tumor growth and promote bone repair.

Direct osteogenesis and immunomodulation dual function via sustained release of naringin from the polymer scaffold.

Many traditional Chinese medicine monomers, such as naringin (NG), can regulate the local immune microenvironment to benefit osteogenesis. However, the rapid release of NG from scaffolds severely influences the osteogenesis-promoting effect. Herein, NG was loaded into mesoporous bioglass (MBG) to achieve sustained release through physical adsorption and the barrier role of mesoporous channels, then MBG loaded with NG was added to poly(L-lactic acid) (PLLA) to fabricate composite scaffolds by selective laser sintering (SLS) technology. The results showed that the NG-MBG/PLLA scaffolds could continuously and slowly release NG for 14 days compared with NG/PLLA scaffolds, and the cumulative release amount for the NG-MBG/PLLA scaffolds was 44.26%. In addition, the NG-MBG/PLLA scaffolds can promote the proliferation and osteogenesis differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs). Meanwhile, the composite scaffolds decreased the reactive oxygen species (ROS) level of RAW264.7 under the stimulation of lipopolysaccharide (LPS) and significantly suppressed interleukin-6 (IL-6) and enhanced arginase-1 (Arg-1) protein expressions. Moreover, calcium nodule and alkaline phosphatase production of mBMSCs in a macrophage-conditioned medium for the NG-MBG/PLLA group also evidently increased compared with the PLLA and MBG/PLLA groups. These NG sustained-release composite scaffolds with osteo-immunomodulation function have great application prospects in the clinic.

Silver-decorated black phosphorus: a synergistic antibacterial strategy.

Black phosphorus (BP) exhibits great potential as antibacterial materials due to its unique photocatalytic activity. However, the unsatisfactory optical absorption and quick recombination of photoinduced electron-hole pairs restrain its photocatalytic antibacterial performance. In this work, silver nanoparticles (AgNPs) were decorated on BP to construct BP@AgNPs nanohybrids and then introduced into poly-l-lactic acid scaffold. Combining the tunable bandgap of BP and the LSPR effect of AgNPs, BP@AgNPs nanohybrids displayed the broaden visible light absorption. Furthermore, AgNPs acted as electron acceptors could accelerate charge transfer and suppress electron-hole recombination. Therefore, BP@AgNPs nanohybrids achieved synergistically enhanced photocatalytic antibacterial activity under visible light irradiation. Fluorescence probe experiment verified that BP@AgNPs promoted the generation of reactive oxygen species, which could disrupt bacteria membrane, damage DNA and oxide proteins, and finally lead to bacteria apoptosis. As a result, the scaffold possessed strong antibacterial efficiency with a bactericidal rate of 97% under light irradiation. Moreover, the scaffold also exhibited good cytocompatibility. This work highlighted a new strategy to develop photocatalytic antibacterial scaffold for bone implant application.

Construction of a stereocomplex between poly(D-lactide) grafted hydroxyapatite and poly(L-lactide): toward a bioactive composite scaffold with enhanced interfacial bonding.

The poly(L-lactide) (PLLA)/hydroxyapatite (HAP) composite scaffold is expected to combine the favorable compatibility and processability of PLLA with the excellent bioactivity and osteoconductivity of HAP. Unfortunately, the poor interfacial bonding between PLLA and HAP leads to a deterioration in mechanical properties. In this study, poly(D-lactide) (PDLA) was grafted onto the surface of HAP nanoparticles (g-HAP), and then g-HAP was incorporated into PLLA to improve interfacial bonding by stereocomplexation in a scaffold fabricated via selective laser sintering (SLS). The results showed that HAP nanoparticles were grafted with PDLA at a grafting rate of 8.72% by ring-opening polymerization through chemical bonding in the presence of the hydroxyl groups of HAP. The grafted PDLA formed an interfacial stereocomplex with PLLA via an intertwined spiral structure ascribed to their antiparallel and complementary configuration under the action of hydrogen bonding. Consequently, the tensile strength and modulus of the PLLA/g-HAP scaffold increased by 86% and 69%, respectively, compared to those of the PLLA/HAP scaffold. In addition, the scaffold displayed good bioactivity by inducing apatite nucleation and deposition and possessed good cytocompatibility for cell adhesion, growth and proliferation.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

The seeds of Strychnosnux-vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnosnux-vomica. Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

Functionalization of Calcium Sulfate/Bioglass Scaffolds with Zinc Oxide Whisker.

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that the scaffolds presented a strong antibacterial activity after introducing ZnOw, due to the antibacterial factors released from the degradation of ZnO. Moreover, ZnOw was also found to have a distinct reinforcing effect on mechanical properties. This was ascribed to whisker pull-out, crack bridging, crack deflection, crack branching and other toughening mechanisms. In addition, the cell culture experiments showed that the scaffolds with ZnOw had a good biocompatibility.