Pathogenic bacteria in infected microenvironments can severely disrupt the normal progression of wound healing. Sono-responsive nanomaterials have emerged as a promising alternative to conventional antibiotics for combating bacterial infections. Despite the advantageous sono-excited antibacterial properties of n-type barium titanate (BaTiO3, BTO), developing bioheterojunctions (bioHJs) with compatible sono-physical characteristics remains a key strategy for achieving superior sono-antibacterial efficiency. Here, we constructed a novel PN-bioHJ by integrating two-dimensional p-type black phosphorus (BP) with three-dimensional n-type cubic BTO and modifying it onto a poly(lactic-co-glycolic acid) (PLGA) spinning membrane to enhance antibacterial performance under ultrasonic (US) stimulation. The successful construction of PN-bioHJs can significantly enhance the yield of ROS production for sono-responsive antibacterial therapy (SRAT). Additionally, the biodegradable PLGA membrane provides a biocompatible and scalable platform for the acoustic activation of the PN-bioHJs while facilitating localized antibacterial therapy. The designed sono-responsive nanocatalytic membrane demonstrates excellent bactericidal performance with antibacterial rates exceeding 99% under US stimulation. In vivo tests further revealed that the proposed membrane shows excellent biocompatibility and the ability to mitigate pathogenic virulence factors, potentially aiding in the regeneration of infected tissues. This work introduces a promising strategy for leveraging acoustically activated membranes in biomedical applications, paving the way for advanced solutions to combat antibiotic resistance.
Developing hydrogel dressings with the capabilities to accommodate irregular wounds and provide a cascade disinfective-regenerative microenvironment for wound repair is of great importance to combating pathogenic bacteria-infected wounds but remains an ongoing challenge. To address the conundrum, we devise a molybdoenzymes-emulating bio-heterojunction (M-bioHJ) doped double network (DN) hydrogel dressing for bacterial-infected wound healing. The near-infrared (NIR) photothermal effect of the M-bioHJ facilitates the exchange of multiple dynamic crosslinking sites in the hydrogel, endowing the hydrogel with photo-remote reprocessing capabilities to completely accommodate the encountered irregular wounds and ultimately accomplish the admirable therapeutic effect. Meanwhile, the introduced M-bioHJ shows NIR light-enhanced photodynamic activity to induce a massive engendering of reactive oxygen species (ROS), allowing rapid sterilization without reliance on exogenous hydrogen peroxide. Furthermore, the Mo ions released from the M-bioHJ-encapsulated hydrogel can play a crucial role in reprogramming the macrophage phenotype and determining tissue regeneration. Both in vitro and in vivo evidences authenticate the accelerated healing potential of infected wounds through the synergistic effects of photo-reprocessing, disinfection, and macrophage-reprogramming facilitated by the hydrogel. These findings highlight the promising application prospects of such neoteric M-bioHJ-encapsulated hydrogel dressings for wound disinfection and tissue regeneration.
After an osteosarcoma resection, the risks of cancer recurrence, postoperative infection, and large bone loss still threaten patients' health. Conventional treatment relies on implanting orthopedic materials to fill bone defects after surgery, but it has no ability of destroying residual tumor cells and preventing bacterial invasion. To tackle this challenge, here, we develop a novel multifunctional implant (SP@MX/GelMA) that mainly consists of MXene nanosheets, gelatin methacrylate (GelMA) hydrogels, and bioinert sulfonated polyetheretherketone (SP) with the purpose of facilitating tumor cell death, combating pathogenic bacteria, and promoting osteogenicity. Because of the synergistic photothermal effects of MXene and polydopamine (pDA), osteosarcoma cells are effectively killed on the multifunctional coatings under 808 nm near-infrared (NIR) irradiation through thermal ablation. After loading tobramycin (TOB), the SP@MX-TOB/GelMA implants display robust antibacterial properties against Gram-negative/Gram-positive bacteria. More importantly, the multifunctional implants are demonstrated to have superior cytocompatibility and osteogenesis-promoting capability in terms of cell replication, spreading, alkaline phosphatase activity, calcium matrix mineralization, and in vivo osseointegration. Accordingly, such photothermally controlled multifunctional implants not only defeat osteosarcoma cells and bacteria but also intensify osteogenicity, which hold a greatly promising countermeasure for curing postoperative tissue lesion from an osteosarcoma excision.
The ideal bone tissue engineering scaffolds are long-cherished with the properties of suitable three-dimensional structure, controlled biodegradability and acceptable biocompatibility. Here, the porous biphasic α/β-tricalcium phosphate (α/β-TCP) bioceramics with different two phase ratios of α-tricalcium phosphate (α-TCP) and β-tricalcium phosphate (β-TCP) were successfully synthesised by heating an amorphous calcium phosphate (ACP) precursor containing pore-forming agent. The crystalline and morphological characterisation revealed that α- and β-TCP phases co-existed in the α/β-TCP bioceramics and they had interconnected pore structures with size between 200 and 500 μm. The degradation behaviours of the biphasic α/β-TCPs were also probed in physiological saline solution under static and dynamic environments for the first time. The results showed that dissolution rate of α/β-TCP bioceramics in dynamic environment was higher than that under static conditions. Compared with monophasic TCP ceramics, these porous α/β-TCP bioceramics displayed a tailored dissolution rate through tuning the proportion of each TCP phases (α and β) in the materials, and the Ca degradation concentration correlated with the circulating flow velocity. Further, the degradation profile of porous α/β-TCPs was well-described by Johnson–Mehl–Avrami (JMA) method. The porous biphasic α/β-TCP bioceramics with controllable degradation performance hold great potential to be applied in bone tissue engineering.
Osteoclasts demineralize and resorb bone once they attach to its surface. However, it’s still unclear how the osteoclasts choose the specific sites for their attachments. It is postulated in this article that the decreased extracellular free ionized calcium concentration (Ca 2+ [e] ) can provide a microenvironment for osteoclasts to recognize and then initiate the attachment process. The osteoclasts initially attach to the bone surface via integrating its integrin α v β 3 and RGD containing ligands in bone matrix. Through the interaction with RGD-containing ligand, the integrin α v β 3 forms carboxylate oxygen noncovalent, which is further stabilized by accompanied electrostatic interaction between the Ca 2+ and the β 3 subunit. There are two types of cation-binding sites on the β 3 subunit: the high affinity Ca 2+ binding site (“LC” site) that activates the osteoclasts by promoting the combination; the low affinity Ca 2+ binding site (“I” site, also named ADMIDAS) that deactivates the osteoclasts by dissociating the combination and it can override the “LC” site’s positive effect on osteoclasts when necessary. Normally the Ca 2+ concentration of bone extracellular fluid is maintained within a normal range by osteocytes, keeping the “I” sites activated. When the osteocytes’ function stalls and the ambient Ca 2+ concentration falls below the affinity discrimination threshold between the “I” site and the “LC” site, the “LC” site’s promoting function starts to out compete the “I” site in its inhibitory effect, in which case the inactive integrin α v β 3 turns into an extended active form and the osteoclasts start to attach, signifying the initiation of bone resorption.
The dental zirconia–leucite composites were synthesized by high temperature solid-state method using potash feldspar, potassium carbonate and zirconia as raw materials. The mechanical properties and the coefficient of thermal expansion (CTE) of the prepared zirconia–leucite composites were tested. The results show that the bending strength, the fracture toughness and the metal–ceramic bonding strength of the prepared samples are about 110 MPa, 3·5 MPa/m 1/2 and 45 MPa, respectively. The CTE was about 13·73×10 –6 °C –1 and close to that of Ni–Cr dental alloy (14·0×10 –6 °C –1 ). The results indicate that the introduction of zirconia is beneficial to the improvement in the mechanical properties and CTE adjustment of porcelain material. The clinical application of the zirconia–leucite composites with good metal–ceramic bonding strength in the dental restoration could be envisioned.