Yunfei Niu

Implant-related infections caused by invasion of bacteria is one of the most common complications during orthopedic interventions, and rapid synostosis is beneficial for stabilizing the implants and resisting infection. Herein, a niobium oxide/polyetherketoneketone composite (NP) was prepared, and submicron/microporous structures were created on NP (forming NPsm) using a picosecond laser. Subsequently, a gallium phytate (GP) coating was deposited on NPsm (forming NPsmG) through phytic acid chelation with gallium ions. The results demonstrated that NPsmG, with improved surface performances, remarkably facilitates the adhesion, migration, proliferation and differentiation of osteoblasts in vitro. Moreover, NPsmG, through its anti-inflammatory effects, promotes M2 macrophage polarization and the secretion of anti-inflammatory factors, thereby establishing a favorable microenvironment for osteogenic differentiation and synostosis. The significant improvements in the cellular responses of osteoblasts and macrophages are attributed to the synergistic effects of the bioactive niobium oxide, submicron/microporous structures and GP coating. NPsmG exhibited good antibacterial performance in vitro and efficiently resisted infection in vivo owing to the sustained release of Ga³⁺ ions. The in vivo experiments further demonstrated that NPsmG remarkably promotes bone regeneration and synostosis. Overall, the integration of a hierarchically structured surface and a GP coating on NPsmG provides a novel strategy for simultaneously promoting osteogenesis and preventing infection, highlighting its potential as a promising orthopedic implant material.

Treatment of infected bone faces dual challenges of biofilm removal and pro-osteogenesis. Herein, a piezoelectric heterojunction of bismuth (Bi)-doped sodium niobate and oxygen-vacancy cerium oxide was constructed, and a heterojunction/polyetherketoneketone composite was prepared as a bone implanted material. The doping of Bi induced the lattice distortion and bandgap reduction of sodium niobate that remarkably enhanced piezoelectricity and sonodynamic efficiency, while oxygen-vacancies caused lattice distortion of cerium oxide that improved nanozyme activities. Under radiation of ultrasound (US), the piezoelectric effect of the composite enhanced sonodynamic performance and oxidant nanozyme activities that generated abundant reactive oxygen species (ROS) for eradicating bacteria and eliminating biofilm, and controlling infection, both in vitro and in vivo. Moreover, the piezoelectric effect not only enhanced the anti-oxidant nanozyme activities that scavenged excessive ROS for alleviating oxidative stress, but also stimulated M2 macrophage polarization that created an anti-inflammatory microenvironment for osteogenesis. Furthermore, the piezoelectric stimulation of composite boosted cellular responses (osteoblasts differentiation, angiogenesis and neurogenesis) in vitro, and promoted neuro-vascularized bone regeneration in vivo. Consequently, US-triggered piezoelectric effect of the composite displays promising potential for treatment of infected bone. This study provides a novel strategy to design piezoelectric biomaterials with nanozyme activities for preventing infection and encouraging neurovascular ossification.

A piezoelectric nanozyme is a novel biomaterial with the integration of piezoelectricity and nanozyme activity that has the capability of killing bacteria and promoting cell responses under a mechanical stimulus and exhibits great prospects in tissue regeneration. Herein, a piezoelectric nanozyme of bismuth sulfide (BS) with cationic vacancies (VBS) was synthesized, which exhibits enhanced piezoelectricity and nanozyme activities compared with BS. Moreover, a piezoelectric hydrogel of VBS and phenylboronic acid grafted sodium alginate-arginine (VBS-PSA) was prepared. Triggered by ultrasound (US) with high power (>0.5 W cm⁻²), VBS-PSA produces a large amount of reactive oxygen species (ROS) through both piezoelectricity-enhanced sonodynamic efficiency and peroxidase-like (POD-like) activity, thereby displaying the powerful antibacterial capability. However, under low-power US (≤0.5 W cm⁻²), the piezoelectric effect of VBS-PSA generates electrical signals that significantly stimulate the osteoblast responses (proliferation and osteoblast differentiation) and enhance catalase-like (CAT-like) activity for scavengers of ROS and generation of oxygen, thereby creating a favorable microenvironment for cell growth. Our study presents a novel strategy to apply the piezoelectric effect of hydrogels for enhancing sonodynamic efficiency and nanozyme activities that synergistically kill bacteria and stimulate osteoblast responses. The piezoelectric hydrogel would have great potential for the repair of infected bone defects.

The development of an artificial ligament with a multifunction of promoting bone formation, inhibiting bone resorption, and preventing infection to obtain ligament-bone healing for anterior cruciate ligament (ACL) reconstruction still faces enormous challenges. Herein, a novel artificial ligament based on a PI fiber woven fabric (PIF) was fabricated, which was coated with a phytic acid-gallium (PA-Ga) network via a layer-by-layer assembly method (PFPG). Compared with PIF, PFPG with PA-Ga coating significantly suppressed osteoclastic differentiation, while it boosted osteoblastic differentiation in vitro. Moreover, PFPG obviously inhibited fibrous encapsulation and bone absorption while accelerating new bone regeneration for ligament-bone healing in vivo. PFPG remarkably killed bacteria and destroyed biofilm, exhibiting excellent antibacterial properties in vitro as well as anti-infection ability in vivo, which were ascribed to the release of Ga ions from the PA-Ga coating. The cooperative effect of the surface characteristics (e.g., hydrophilicity/surface energy and protein absorption) and sustained release of Ga ions for PFPG significantly enhanced osteogenesis while inhibiting osteoclastogenesis, thereby achieving ligament-bone integration as well as resistance to infection. In summary, PFPG remarkably facilitated osteoblastic differentiation, while it suppressed osteoclastic differentiation, thereby inhibiting osteoclastogenesis for bone absorption while accelerating osteogenesis for ligament-bone healing. As a novel artificial ligament, PFPG represented an appealing option for graft selection in ACL reconstruction and displayed considerable promise for application in clinics.

How to treat cartilage defects effectively in the clinic has become a great challenge. Due to the lack of blood vessels, nerves and the lymphatic system, self-repair of cartilage usually cannot be achieved when damaged. Therefore, identifying a potential therapeutic method for cartilage regeneration is necessary. In the present study, wheat protein (WP)-based hydrogels loaded with magnesium silicate (MS) and glucosamine (GA) were fabricated via the sol-gel method, and the restorative effect of the resulting hydrogel composite (MSWG) on cartilage defects was also evaluated. The mechanical strength, biodegradability and hydrophilicity of MSW have been largely improved. Moreover, the porous structure of MSWG promotes cell adhesion, proliferation and migration. MSWG promotes the expression of genes and proteins related to chondrogenic differentiation in vitro To evaluate the effect of MSWG on cartilage regeneration in vivo, rabbit knee cartilage defects were established in this study, and MSWG composites were implanted into the defects. More cartilage and subchondral bone appeared around the defect in the MSWG group, and the chondrocytes seemed to mature. In conclusion, the addition of GA to MSW improved its physicochemical properties and biocompatibility. The synergistic effect of hydrogel composites has been proven to promote the expression of chondrogenic biomarkers and accelerate the repair of cartilage defects. MSWG hydrogel composites, as potential candidates, are promising for application in cartilage regeneration.

Absorbable polymers have attracted increasing attention in the field of bone regeneration in recent years for their degradation. Compared with other degradable polymers, polypropylene carbonate (PPC) has several advantages such as biodegradation and relatively cheap raw materials. Most importantly, PPC can degrade into water and carbon dioxide totally which does not give rise to local inflammation and bone resorption in vivo. However, pure PPC has not presented excellent osteoinductivity properties. In order to enhance the osteoinductivity of PPC, silicon nitride (SiN) was employed due to its excellent mechanical properties, biocompatibility and osteogenesis compared with the other common materials such as hydroxyapatite and calcium phosphate ceramics. In this study, composites of PPC mixed with different contents of SiN were prepared successfully (PSN10 with 10 wt% SiN content, and PSN20 with 20 wt% SiN content). The characterization of the composites suggested that PPC mixed with SiN evenly and PSN composites presented stable properties. The results in vitro revealed that the PSN20 composite possessed satisfactory biocompatibility and exerted better osteogenic differentiation effects on adipose-derived stem cells (ADSCs). In particular, the PSN20 composite accelerated the healing of bone defects better and degraded with the process of bone healing in vivo. Overall, the PSN20 composite exhibited better biocompatibility, induced osteogenic differentiation of ADSCs and promoted healing of bone defects, due to which the PSN composite is considered as a potential candidate for treating bone defects in the field of bone tissue engineering.