MXene-based nanozymes have garnered considerable attention because of their potential environmental and biomedical applications. These materials encompass alluring and manageable catalytic performances and physicochemical features, which make them suitable as (bio)sensors with high selectivity/sensitivity and efficiency. MXene-based structures with suitable electrical conductivity, biocompatibility, large surface area, optical/magnetic properties, and thermal/mechanical features can be applied in designing innovative nanozymes with area-dependent electrocatalytic performances. Despite the advances made, there is still a long way to deploy MXene-based nanozymes, especially in medical and healthcare applications; limitations pertaining the peroxidase-like activity and sensitivity/selectivity may restrict further practical applications of pristine MXenes. Thus, developing an efficient surface engineering tactic is still required to fabricate multifunctional MXene-based nanozymes with excellent activity. To obtain MXene-based nanozymes with unique physicochemical features and high stability, some crucial steps such as hybridization and modification ought to be performed. Notably, (nano)toxicological and long-term biosafety analyses along with clinical translation studies still need to be comprehensively addressed. Although very limited reports exist pertaining to the biomedical potentials of MXene-based nanozymes, the future explorations should transition toward the extensive research and detailed analyses to realize additional potentials of these structures in biomedicine with a focus on clinical and industrial aspects. In this perspective, therapeutic, diagnostic, and theranostic applications of MXene-based nanozymes are deliberated with a focus on future perspectives toward more successful clinical translational studies. The current state-of-the-art biomedical advances in the use of MXene-based nanozymes, as well as their developmental challenges and future prospects are also highlighted. In view of the fascinating properties of MXene-based nanozymes, these materials can open significant new opportunities in the future of bio- and nanomedicine. 

https://link.springer.com/content/pdf/10.1007/s40820-022-00958-7.pdf

MXene-Based Composites as Nanozymes in Biomedicine: A Perspective

Ideal periosteum materials are required to participate in a sequence of bone repair-related physiological events, including the initial immune response, endogenous stem cell recruitment, angiogenesis, and osteogenesis. However, conventional tissue-engineered periosteal materials have difficulty achieving these functions by simply mimicking the periosteum via structural design or by loading exogenous stem cells, cytokines, or growth factors. Herein, we present a novel biomimetic periosteum preparation strategy to comprehensively enhance the bone regeneration effect using functionalized piezoelectric materials. The resulting biomimetic periosteum possessing an excellent piezoelectric effect and improved physicochemical properties was prepared using a biocompatible and biodegradable poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) polymer matrix, antioxidized polydopamine-modified hydroxyapatite (PHA), and barium titanate (PBT), which were further incorporated into the polymer matrix to fabricate a multifunctional piezoelectric periosteum by a simple one-step spin-coating method. The addition of PHA and PBT dramatically enhanced the physicochemical properties and biological functions of the piezoelectric periosteum, resulting in improved surface hydrophilicity and roughness, enhanced mechanical performance, tunable degradation behavior, and stable and desired endogenous electrical stimulations, which is conducive to accelerating bone regeneration. Benefiting from endogenous piezoelectric stimulation and bioactive components, the as-fabricated biomimetic periosteum demonstrated favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro, which not only promoted adhesion, proliferation, and spreading as well as osteogenesis of mesenchymal stem cells (MSCs) but also effectively induced M2 macrophage polarization, thereby suppressing reactive oxygen species (ROS)-induced inflammatory reactions. Through in vivo experiments, the biomimetic periosteum with endogenous piezoelectric stimulation synergistically accelerated the formation of new bone in a rat critical-sized cranial defect model. The whole defect was almost completely covered by new bone at 8 weeks post treatment, with a thickness close to that of the host bone. Collectively, with its favorable immunomodulatory and osteogenic properties, the biomimetic periosteum developed here represents a novel method to rapidly regenerate bone tissue using piezoelectric stimulation. 

Bioinspired Piezoelectric Periosteum to Augment Bone Regeneration via Synergistic Immunomodulation and Osteogenesis

In recent years, a variety of novel materials and processing technologies have been developed to prepare tissue engineering scaffolds for bone defect repair. Among them, nanofibers fabricated via electrospinning technology have attracted much interest owing to the unique feature of highly mimicking the natural bone extracellular matrix. In particular, many achievements have been made in this field over the past several years. Therefore, this review aims to summarize the most recent advances and highlights of electrospun nanofibers in bone regeneration applications, by focusing on their material compositions (synthetic polymers, natural polymers, composite nanofibers, and hybrid nanofibers), structural regulation strategies (aligned structures, core-shell structures, gradient structures, and three-dimensional structures), function regulation achievements (biomineralization, osteogenesis, vascularization, immunomodulatory, and anti-infection), and combination with other emerging scaffold fabrication technologies (3D printing, electrospraying, and microfluidics). Finally, the future challenges of nanofibrous scaffolds in this field are also discussed briefly. It is anticipated that this review will provide useful insights into the future development of nanofibrous scaffolds in tissue engineering and bone regeneration applications.

Electrospun nanofibers for bone regeneration: from biomimetic composition, structure to function.

Comprehensive utilization and biomedical application of MXenes - A systematic review of cytotoxicity and biocompatibility

The skeletal system is essential for preserving body structure and facilitating mobility; however, bone diseases frequently result in significant disabilities, necessitating the investigation into biomaterials for bone restoration. Nevertheless, these biomaterials may elicit immune reactions that obstruct the healing process. Macrophages assume a pivotal role in modulating inflammation and sustaining immune homeostasis essential for bone regeneration. A comprehensive understanding of the molecular interactions between biomaterials and macrophages is imperative for the development of sophisticated biomaterials designed to regulate the bone immune environment and promote bone remodeling. This review delves into the generation, polarization, and interaction of macrophages with principal cell types implicated in osteogenesis, detailing the molecular mechanisms by which macrophages influence bone repair and their response to biomaterials. Additionally, it discusses strategies for the precise modulation of macrophage functionality via intelligent mechanisms, and outlines the challenges and constraints in designing biomaterials that integrate bone immune functions. By elucidating these mechanisms and challenges, the review lays the groundwork for the creation of advanced biomaterials endowed with smart bone immunomodulatory capabilities, heralding novel approaches for the treatment of bone defects and the advancement of bone regeneration therapies. 

Macrophage-mediated immunomodulation in biomaterial-assisted bone repair: Molecular insights and therapeutic prospects

Drug-free antibacterial strategies are of great significance for pathogenic bacterial infection treatment in clinical practice. Phototherapy with antibacterial function plays a vital role in mainstream germicidal research. However, phototherapy could lead to residual heat and excess reactive oxygen species (ROS), which are the main side-effects during antibacterial treatment. Unique CoFe2O4/MXene (CM) nanoenzymes, which were fabricated with electrostatic interactions, have been designed to conquer those challenges caused by side-effects of phototherapy in our research. The CM nanoenzymes possess many promising properties including photothermal and photodynamic induced phototherapy and mimic peroxidase (POD), glutathione oxidase (GSHOx), and catalase (CAT). Upon treatment with near-infrared (NIR) light, CM nanoenzymes can create a local high-temperature circumstance as well as raise bacterial membrane permeability. Furthermore, the photodynamic process and multi-enzyme-mimicking activities of CM enzymes boost the interbacterial ROS level. Herein, bacteria can hardly survive in synergistic phototherapy and multi-enzyme-mimicking catalytic therapy in vitro and in vivo. Meanwhile, the CM nanoenzymes exhibit excellent biocompatibility in vitro and in vivo. Overall, this research establishes a strong foundation for effectively employing nanoenzymes, leading to a new way to cure bacterial infections.

/pdf/multi-activity-cobalt-ferrite-mxene-nanoenzymes-for-drug-14zajlv6.pdf

Multi-activity cobalt ferrite/MXene nanoenzymes for drug-free phototherapy in bacterial infection treatment

Implanted bone scaffolds or their biodegradation products may disturb the sequential functions of distinct macrophage phenotypes and cause improper timing of macrophage activation, resulting in delayed or dysfunctional bone regeneration. Although spatiotemporal manipulation of the immune response has been recognized as a promising strategy to address this issue, developing satisfactory drug delivery systems with the function of proper timing control on the macrophage phenotype transformation from pro-inflammatory M1 to anti-inflammatory M2 phenotype still remains a challenge. Here, we propose an amphiphilic nanomedicine with dual anti-inflammatory functions and inflammation-responsive drug release properties to spatiotemporally manage the osteoimmunomodulation of the bone scaffold. The nanomedicine enables the modified scaffold to manipulate the immune response in a staged manner, not only avoiding the overinhibition of M1 macrophages in the initial phase but also facilitating its polarization to M2 phenotype, as well as exhibiting full-course inhibition on later biodegradation-induced inflammation. The described immunomodulatory manner attempts to conform to the principle of osteoimmunomodulation, consequently resulting in better in vivo osteogenesis compared with traditional drug delivery systems. We anticipate that this strategy might aid the development of advanced immunomodulatory bone biomaterials.

Spatiotemporal Management of the Osteoimmunomodulation of Fibrous Scaffolds by Loading a Novel Amphiphilic Nanomedicine.

Chronic refractory wounds present substantial clinical difficulties, owing to their complex wound microenvironments featuring bacterial colonization, sustained inflammation, and deficient angiogenesis. Existing treatment options often fall short of concurrently overcoming these interconnected obstacles, underscoring the demand for integrated therapeutic platforms that combine antimicrobial, anti-inflammatory, and pro-angiogenic properties. Drawing inspiration from natural peroxisomes, a lattice-reconstructed Ru-clusters are designed on FeOOH-based self-adaptive artificial peroxisome with programmed reactive oxygen species (ROS) regulation for infectious and inflammatory chronic wounds. Within this architecture, electron-rich Ru clusters and hole-rich FeOOH domains establish an efficient electron-transfer network. Density functional theory calculations demonstrate that this distinctive electronic structure lowers reaction energy barriers, enabling pH-switchable ROS-catalytic behaviors. Under acidic wound pH, LR-RuC@FeOOH catalyzes ROS generation to disrupt bacterial metabolism and eliminate infections, while under neutral conditions, it efficiently scavenges ROS to alleviate oxidative stress and support tissue repair, enabling a logically sequenced therapeutic progression from infection control to inflammation resolution. In vivo experiments using diabetic foot ulcers confirmed that LR-RuC@FeOOH significantly enhanced bacterial clearance, attenuated inflammatory responses, stimulated neovascularization, and accelerated wound closure. These results position LR-RuC@FeOOH as an artificial peroxisome with stage-specific therapies and promising translational potential for the treatment of refractory diabetic wounds and other infection-related pathologies.

Lattice-Reconstructed Ru-Clusters on FeOOH-Based Self-Adaptive Artificial Peroxisome with Programmed ROS Regulation for Infectious and Inflammatory Chronic Wounds.

Bone regenerative biomaterials are essential in treating bone defects as they serve as extracellular matrix (ECM) mimics, creating a favorable environment for cell attachment, proliferation, and differentiation. However, the currently used bone regenerative biomaterials mostly exhibit high stiffness, which may lead to difficulties in degradation and thus increase the risk of foreign body ingestion. In this study, we prepared soft fibrous scaffolds modified with Zn-MOF-74 nanoparticles via electrostatic spinning. The soft fibers (only 1 kPa) permit remodeling under cellular adhesive force, optimizing the mechanical cues in the microenvironment to support cell adhesion and mechanosensing. In addition, the incorporation of Zn-MOF-74 nanoparticles enables the stable and sustained release of zinc ions, promoting stem cell mechanotransduction and osteogenic differentiation. Therefore, the hybrid soft fibers facilitate the regeneration of new bone in the rat femoral defect model, which provides a promising approach for regenerative medicine. 

Promoting Stem Cell Mechanosensing and Osteogenesis by Hybrid Soft Fibers.

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Multi-activity cobalt ferrite/MXene nanoenzymes for drug-free phototherapy in bacterial infection treatment

Spatiotemporal Management of the Osteoimmunomodulation of Fibrous Scaffolds by Loading a Novel Amphiphilic Nanomedicine.

Lattice-Reconstructed Ru-Clusters on FeOOH-Based Self-Adaptive Artificial Peroxisome with Programmed ROS Regulation for Infectious and Inflammatory Chronic Wounds.

Promoting Stem Cell Mechanosensing and Osteogenesis by Hybrid Soft Fibers.