Research progress of miRNA in heart failure: prediction and treatment.

This review summarizes the multiple roles of miRNAs in the prediction and treatment of heart failure (HF), including the molecular mechanisms regulating cell apoptosis, myocardial fibrosis, cardiac hypertrophy and ventricular remodelling, and highlights the importance of miRNAs in the prognosis of HF. In addition, the strategies for alleviating HF with miRNA intervention are discussed. On the basis of the challenges and emerging directions in the research and clinical practice of HF miRNAs, it is proposed that miRNA-based therapy could be a new approach for prevention and treatment of HF.

Shape Sensing and Kinematic Control of a Cable-Driven Continuum Robot Based on Stretchable Capacitive Sensors.

A Cable-Driven Continuum Robot (CDCR) that consists of a set of identical Cable-Driven Continuum Joint Modules (CDCJMs) is proposed in this paper. The CDCJMs merely produce 2-DOF bending motions by controlling driving cable lengths. In each CDCJM, a pattern-based flexible backbone is employed as a passive compliant joint to generate 2-DOF bending deflections, which can be characterized by two joint variables, i.e., the bending direction angle and the bending angle. However, as the bending deflection is determined by not only the lengths of the driving cables but also the gravity and payload, it will be inaccurate to compute the two joint variables with its kinematic model. In this work, two stretchable capacitive sensors are employed to measure the bending shape of the flexible backbone so as to accurately determine the two joint variables. Compared with FBG-based and vision-based shape-sensing methods, the proposed method with stretchable capacitive sensors has the advantages of high sensitivity to the bending deflection of the backbone, ease of implementation, and cost effectiveness. The initial location of a stretchable sensor is generally defined by its two endpoint positions on the surface of the backbone without bending. A generic shape-sensing model, i.e., the relationship between the sensor reading and the two joint variables, is formulated based on the 2-DOF bending deflection of the backbone. To further improve the accuracy of the shape-sensing model, a calibration method is proposed to compensate for the location errors of stretchable sensors. Based on the calibrated shape-sensing model, a sliding-mode-based closed-loop control method is implemented for the CDCR. In order to verify the effectiveness of the proposed closed-loop control method, the trajectory tracking accuracy experiments of the CDCR are conducted based on a circle trajectory, in which the radius of the circle is 55mm. The average tracking errors of the CDCR measured by the Qualisys motion capture system under the open-loop and the closed-loop control are 49.23 and 8.40mm, respectively, which is reduced by 82.94%.

Derotational distal femur osteotomy with medial patellofemoral ligament reconstruction can get good outcomes in the treatment of recurrent patellar dislocation with excessive TT-TG and increased femoral anteversion.

Background: Surgery is the main treatment for recurrent patellar dislocation (PD). However, due to the complexity of anatomical factors, there is still a lack of consensus on the choice of combined surgical methods. This study aimed to compare the clinical and radiological outcomes of medial patellofemoral ligament reconstruction combined with derotational distal femur osteotomies (MPFLR + DDFO) and combined with tibial tubercle osteotomies (MPFLR + TTO) for recurrent PD with increased femoral anteversion angles (FAA) and excessive tibial tubercle-trochlear groove (TT-TG) distance. Methods: In this retrospective analysis, MPFLR + DDFO and MPFLR + TTO patients from 2015 to 2020 were included. Group A (MPFLR + DDFO, n = 42) and B (MPFLR + TTO, n = 46) were formed. Clinical outcomes included physical examinations, functional outcomes (Kujala, Lysholm, International Knee Documentation Committee (IKDC), visual analog scale (VAS) and intermittent and persistent osteoarthritis pain scale (ICOAP), Tegner scores), and complications. The Caton-Deschamps index (CD-I), patellar title angle, patellar congruence angle, patella-trochlear groove distance, TT-TG distance, and FAA were used to assess radiological outcomes. Results: All clinical outcomes improved significantly in both groups, but Group A had significantly better postoperative scores than Group B (Kujala: 89.8 ± 6.4 vs. 82.9 ± 7.4, P < 0.01; Lysholm: 90.9 ± 5.1 vs. 81.3 ± 6.3, P = 0.02; IKDC: 87.3 ± 9.0 vs. 82.7 ± 8.0, P < 0.01; Tegner: 6.0 (5.0, 9.0) vs. 5.0 (4.0, 8.0), P = 0.01). However, there was no significant difference in the VAS and ICOAP scores between the two groups. No dislocation recurrences occurred. Radiological outcomes improved significantly in both groups, but Group A had better outcomes. After surgery, the patellar height of 88.5% (23/26) patients in Group A and 82.8% (24/29) patients in Group B was restored to normal (the Caton-Deschamps index <1.2). Conclusions: Both MPFLR + TTO and MPFLR + DDFO obtained satisfactory clinical and radiological outcomes in the treatment of recurrent PD with increased FAA and excessive TT-TG. However, the outcomes of MPFLR + DDFO were better and should be considered a priority. MPFLR + TTO may be not necessary for such patients.

Role of tumor cell pyroptosis in anti-tumor immunotherapy.

Peripheral tumor-specific CD8+ T cells often fail to infiltrate into tumor parenchyma due to the immunosuppression of tumor microenvironment (TME). Meanwhile, a significant portion of tumor-specific CD8+ T cells infiltrated into TME are functionally exhausted. Despite the enormous success of anti-PD-1/PD-L1 immune-checkpoint blockade (ICB) treatment in a wide variety of cancer types, the majority of patients do not respond to this treatment largely due to the failure to efficiently drive tumor-specific CD8+ T cell infiltration and reverse their exhaustion states. Nowadays, tumor cell pyroptosis, a unique cell death executed by pore-forming gasdermin (GSDM) family proteins dependent or independent on inflammatory caspase activation, has been shown to robustly promote immune-killing of tumor cells by enhancing tumor immunogenicity and altering the inflammatory state in the TME, which would be beneficial in overcoming the shortages of anti-PD-1/PD-L1 ICB therapy. Therefore, in this review we summarize the current progresses of tumor cell pyroptosis in enhancing immune function and modulating TME, which synergizes anti-PD-1/PD-L1 ICB treatment to achieve better anti-tumor effect. We also enumerate several strategies to better amply the efficiency of anti-PD-1/PD-L1 ICB therapy by inducing tumor cell pyroptosis.

Utilizing microbial metabolite in catalytic cascade synthesis of conjugated oligomers for In-Situ regulation of biological activity.

Despite the advances of multistep enzymatic cascade reactions, their incorporation with abiotic reactions in living organisms remains challenging in synthetic biology. Herein, we combined microbial metabolic pathways and Pd-catalyzed processes for in-situ generation of bioactive conjugated oligomers. Our biocompatible one-pot coupling reaction utilized the fermentation process of engineered E. coli that converted glucose to styrene, which participated in the Pd-catalyzed Heck reaction for in-situ synthesis of conjugated oligomers. This process serves a great interest in understanding resistance evolution by utilizing the inhibitory activity of the synthesized conjugated oligomers. The approach allows for the in-situ combination of biological metabolism and CC coupling reactions, opening up new possibilities for the biosynthesis of unnatural molecules and enabling the in-situ regulation of the bioactivity of the obtained products.

Sensing, Imaging, and Therapeutic Strategies Endowing by Conjugate Polymers for Precision Medicine.

Conjugated polymers (CPs) have promising applications in biomedical fields, such as disease monitoring, real-time imaging diagnosis, and disease treatment. As a promising luminescent material with tunable emission, high brightness and excellent stability, CPs are widely used as fluorescent probes in biological detection and imaging. Rational molecular design and structural optimization have broadened absorption/emission range of CPs, which are more conductive for disease diagnosis and precision therapy. This review provides a comprehensive overview of recent advances in the application of CPs, aiming to elucidate their structural and functional relationships. The fluorescence properties of CPs and the mechanism of detection signal amplification are first discussed, followed by an elucidation of their emerging applications in biological detection. Subsequently, CPs-based imaging systems and therapeutic strategies are illustrated systematically. Finally, recent advancements in utilizing CPs as electroactive materials for bioelectronic devices are also investigated. Moreover, the challenges and outlooks of CPs for precision medicine are discussed. Through this systematic review, it is hoped to highlight the frontier progress of CPs and promote new breakthroughs in fundamental research and clinical transformation.

Organic Semiconducting Polymers for Augmenting Biosynthesis and Bioconversion.

Solar-driven biosynthesis and bioconversion are essential for achieving sustainable resources and renewable energy. These processes harness solar energy to produce biomass, chemicals, and fuels. While they offer promising avenues, some challenges and limitations should be investigated and addressed for their improvement and widespread adoption. These include the low utilization of light energy, the inadequate selectivity of products, and the limited utilization of inorganic carbon/nitrogen sources. Organic semiconducting polymers offer a promising solution to these challenges by collaborating with natural microorganisms and developing artificial photosynthetic biohybrid systems. In this Perspective, we highlight the latest advancements in the use of appropriate organic semiconducting polymers to construct artificial photosynthetic biohybrid systems. We focus on how these systems can enhance the natural photosynthetic efficiency of photosynthetic organisms, create artificial photosynthesis capability of nonphotosynthetic organisms, and customize the value-added chemicals of photosynthetic synthesis. By examining the structure-activity relationships and emphasizing the mechanism of electron transfer based on organic semiconducting polymers in artificial photosynthetic biohybrid systems, we aim to shed light on the potential of this novel strategy for artificial photosynthetic biohybrid systems. Notably, these coupling strategies between organic semiconducting polymers and organisms during artificial photosynthetic biohybrid systems will pave the way for a more sustainable future with solar fuels and chemicals.

Bioactive prosthesis interface compositing variable-stiffness hydrogels regulates stem cells fates to facilitate osseointegration through mechanotransduction.

Fluid hydrogel is proper to be incorporated with rigid porous prosthesis interface, acting as a soft carrier to support cells and therapeutic factors, to enhance osseointegration. In the previous study, we innovatively utilized self-healing supramolecular hydrogel as 3D cell culture platform to incorporate with 3D printed porous titanium alloy scaffold, constructing a novel bioactive interface. However, the concrete relationship and mechanism of hydrogel stiffness influencing cellular behaviors of bone marrow mesenchymal stem cells (BMSCs) within the interface are still inconclusive. Herein, we synthesized a series of supramolecular hydrogels with variable stiffness as extracellular matrix (ECM) to enhance the osseointegration of 3D printed prosthesis interface. BMSCs exposed to stiff hydrogel received massive environmental mechanical stimulations, subsequently transducing biophysical cues into biochemical signal through mechanotransduction process. The mRNA-sequencing analysis revealed that the activated FAK-MAPK pathway played significant roles in promoting osteogenic differentiation, thus contributing to a strong osseointegration. Our work preliminarily demonstrated the relationship of ECM stiffness and osteogenic differentiation trend of BMSCs, and optimized stiffness of hydrogel within a certain range benefitting for osteogenic differentiation and prosthesis interface osseointegration, providing a valuable insight into the development of orthopaedic implants equipped with osteogenic mechanotransduction ability.

Conjugated Molecules Based Multi-Component Artificial Photosynthesis System for Producing Multi-Objective Products.

The development of artificial photosynthesis systems that mimics natural photosynthesis can help address the issue of energy scarcity by efficiently utilizing solar energy. Here, it presents liposomes-based artificial photosynthetic nanocapsules (PSNC) integrating photocatalytic, chemical catalytic, and biocatalytic systems through one-pot method. The PSNC contains 5,10,15,20-tetra(4-pyridyl) cobalt-porphyrin, tridipyridyl-ruthenium nitrate, oligo-pphenyl-ethylene-rhodium complex, and creatine kinase, efficiently generating oxygen, nicotinamide adenine dinucleotide (NADH), and adenosine triphosphate with remarkable enhancements of 231%, 30%, and 86%, compared with that of molecules mixing in aqueous solution. Additionally, the versatile PSNC enables simulation of light-independent reactions, achieving a controllable output of various target products. The regenerated NADH within PSNC further facilitates alcohol dehydrogenase, yielding methanol with a notable efficiency improvement of 37%. This work introduces a promising platform for sustainable solar energy conversion and the simultaneous synthesis of multiple valuable products in an ingenious and straightforward way.

A variable mineralization time and solution concentration intervene in the microstructure of biomimetic mineralized collagen and potential osteogenic microenvironment.

The absence of a conducive bone formation microenvironment between fractured ends poses a significant challenge in repairing large bone defects. A promising solution is to construct a bone formation microenvironment that mimics natural bone tissue. Biomimetic mineralized collagen possesses a chemical composition and microstructure highly similar to the natural bone matrix, making it an ideal biomimetic bone substitute material. The microstructure of biomimetic mineralized collagen is influenced by various factors, and its biomineralization and microstructure, in turn, affect its physicochemical properties and biological activity. We aimed to utilize mineralization time and solution concentration as variables and employed the polymer-induced liquid precursor strategy to fabricate mineralized collagen with diverse microstructures, to shed light on how mineralization parameters impact the material microstructure and physicochemical properties. We also investigated the influence of microstructure and physicochemical properties on cell biocompatibility and the bone-forming microenvironment. Through comprehensive characterization, we examined the physical and chemical properties of I-EMC under various mineralization conditions and assessed the in vitro and in vivo biocompatibility and osteogenic performance. By investigating the relationship between mineralization parameters, material physicochemical properties, and osteogenic performance, we revealed how microstructures influence cellular behaviors like biocompatibility and osteogenic microenvironment. Encouragingly, mineralization solutions with varying concentrations, stabilized by polyacrylic acid, successfully produced intrafibrillar and extrafibrillar mineralized collagen. Compared to non-mineralized collagen, all mineralized samples demonstrated improved bone-forming performance. Notably, samples prepared with a 1× mineralization solution exhibited relatively smooth surfaces with even mineralization. Extending the mineralization time enhanced the degree of mineralization and osteogenic performance. Conversely, samples prepared with a 2× mineralization solution had rough surfaces with large calcium phosphate particles, indicating non-uniform mineralization. Overall, our research advances the potential for commercial production of mineralized collagen protein products, characterized by dual biomimetic properties, and their application in treating various types of bone defects.

Effects of extreme cyclic loading on the cushioning performance of human heel pads under engineering test condition.

Human heel pads commonly undergo cyclic loading during daily activities. Low cyclic loadings such as daily human walking tend to have less effect on the mechanical properties of heel pads. However, the impact of cyclic loading on cushion performance, a vital biomechanical property of heel pads, under engineering test condition remains unexplored. Herein, dynamic mechanical measurements and finite element (FE) simulations were employed to explore this phenomenon. It was found that the wavy collagen fibers in the heel pad will be straightened under cycle compression loading, which resulted in increased stiffness of the heel pad. The stiffness of the heel pads demonstrated an inclination to escalate over a span of 50,000 loading cycles, consequently resulting in a corresponding increase in peak impact force over the same loading cycles. Sustained cyclic loading has the potential to result in the fracturing of the straightened collagen fibers, this collagen breakage may diminish the stiffness of the heel pad, leading to a reduction in peak impact force. This work enhances understanding of the biomechanical functions of human heel pad and may provide potential inspirations for the innovative development of healthcare devices for foot complex.

3D-printed PCL scaffolds with anatomy-inspired bionic stratified structures for the treatment of growth plate injuries.

The growth plate is a cartilaginous tissue with three distinct zones. Resident chondrocytes are highly organized in a columnar structure, which is critical for the longitudinal growth of immature long bones. Once injured, the growth plate may potentially be replaced by bony bar formation and, consequently, cause limb abnormalities in children. It is well-known that the essential step in growth plate repair is the remolding of the organized structure of chondrocytes. To achieve this, we prepared an anatomy-inspired bionic Poly(ε-caprolactone) (PCL) scaffold with a stratified structure using three-dimensional (3D) printing technology. The bionic scaffold is engineered by surface modification of NaOH and collagen Ⅰ (COL Ⅰ) to promote cell adhesion. Moreover, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are loaded in the most suitable ratio of 1:3 for growth plate reconstruction. Based on the anatomical structure of the growth plate, the bionic scaffold is designed to have three regions, which are the small-, medium-, and large-pore-size regions. These pore sizes are used to induce BMSCs to differentiate into similar structures such as the growth plate. Remarkably, the X-ray and histological results also demonstrate that the cell-loaded stratified scaffold can successfully rebuild the structure of the growth plate and reduce limb abnormalities, including limb length discrepancies and angular deformities in vivo. This study provides a potential method of preparing a bioinspired stratified scaffold for the treatment of growth plate injuries.

Self-Powered Biohybrid Systems Based on Organic Materials for Sustainable Biosynthesis.

Sustainable energy conversion and effective biosynthesis for value-added chemicals have attracted considerable attention, but most biosynthesis systems cannot work independently without external power. In this work, a self-powered biohybrid system based on organic materials is designed and constructed successfully by integrating electroactive microorganisms with electrochemical devices. Among them, the hybrid living materials based on S. oneidensis/poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene chloride] (PMNT) biofilms for microbial fuel cells played a crucial role in electrocatalytic biocurrent generation by using biowaste as the only energy source. Without any external power supplies, the self-powered biohybrid systems could generate, convert, and store electrical energy for effective photosynthetic regulation and sustained chemical production. This work provides a new strategy to combine comprehensive renewable energy production with chemical manufacturing without an external power source in the future.

[Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Biosynthesis of Multifunctional Transformable Peptides for Inducing Tumor Cell Apoptosis.

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein-based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein-based material P1 is comprised of a ß-sheet-forming peptide KLVFF, pro-apoptotic protein BAK, and GFP along with targeting moieties. The self-assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria-dependent apoptosis through Bcl-2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1-expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide-based enzyme-catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics.

Bisphosphonate-incorporated coatings for orthopedic implants functionalization.

Bisphosphonates (BPs), the stable analogs of pyrophosphate, are well-known inhibitors of osteoclastogenesis to prevent osteoporotic bone loss and improve implant osseointegration in patients suffering from osteoporosis. Compared to systemic administration, BPs-incorporated coatings enable the direct delivery of BPs to the local area, which will precisely enhance osseointegration and bone repair without the systemic side effects. However, an elaborate and comprehensive review of BP coatings of implants is lacking. Herein, the cellular level (e.g., osteoclasts, osteocytes, osteoblasts, osteoclast precursors, and bone mesenchymal stem cells) and molecular biological regulatory mechanism of BPs in regulating bone homeostasis are overviewed systematically. Moreover, the currently available methods (e.g., chemical reaction, porous carriers, and organic material films) of BP coatings construction are outlined and summarized in detail. As one of the key directions, the latest advances of BP-coated implants to enhance bone repair and osseointegration in basic experiments and clinical trials are presented and critically evaluated. Finally, the challenges and prospects of BP coatings are also purposed, and it will open a new chapter in clinical translation for BP-coated implants.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Aggregation-Induced Emission (AIE), Life and Health.

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Increased Nitrogenase Activity in Solar-Driven Biohybrids Containing Non-photosynthetic Bacteria and Conducting Polymers.

A conductive polymer-based photosynthetic biohybrid is constructed to enhance biological nitrogen fixation by increasing nitrogenase activity in the non-photosynthetic bacterium Azotobacter Chroococcum (A. Chroococcum). The light-harvesting cationic poly(fluorene-alt-phenylene) (PFP) electrostatically binds to the surface of the bacteria and possesses satisfactory conductivity to facilitate electron transfer to the bacterium, promoting the nitrogen fixation pathway through redox proteins on the surface of the bacteria when under illumination. Therefore, the nitrogenase activity, hydrogen, NH4 + -N and L-amino acids production are increased by 260 %, 37 %, 44 %, and 47 %, respectively. The expression levels of nifD and nifK encoding molybdenum-iron (MoFe) protein and relevant nitrogen-fixing proteins are up-regulated. These photoactive conductive polymer-bacteria biohybrids provide a new method for improving the biological nitrogen fixation capability of non-photosynthetic nitrogen-fixing bacteria.

Functionalization of biomimetic mineralized collagen for bone tissue engineering.

Mineralized collagen (MC) is the basic unit of bone structure and function and is the main component of the extracellular matrix (ECM) in bone tissue. In the biomimetic method, MC with different nanostructures of neo-bone have been constructed. Among these, extra-fibrous MC has been approved by regulatory agencies and applied in clinical practice to play an active role in bone defect repair. However, in the complex microenvironment of bone defects, such as in blood supply disorders and infections, MC is unable to effectively perform its pro-osteogenic activities and needs to be functionalized to include osteogenesis and the enhancement of angiogenesis, anti-infection, and immunomodulation. This article aimed to discuss the preparation and biological performance of MC with different nanostructures in detail, and summarize its functionalization strategy. Then we describe the recent advances in the osteo-inductive properties and multifunctional coordination of MC. Finally, the latest research progress of functionalized biomimetic MC, along with the development challenges and future trends, are discussed. This paper provides a theoretical basis and advanced design philosophy for bone tissue engineering in different bone microenvironments.