Bone Tissue Engineering Strategies Research Articles

The treatment efficacy of bone tissue engineering strategy for repairing segmental bone defects under diabetic condition.

Diabetes mellitus is a systematic disease which exert detrimental effect on bone tissue. The repair and reconstruction of bone defects in diabetic patients still remain a major clinical challenge. This study aims to investigate the potential of bone tissue engineering approach to improve bone regeneration under diabetic condition. In the present study, decalcified bone matrix (DBM) scaffolds were seeded with allogenic fetal bone marrow-derived mesenchymal stem cells (BMSCs) and cultured in osteogenic induction medium to fabricate BMSC/DBM constructs. Then the BMSC/DBM constructs were implanted in both subcutaneous pouches and large femoral bone defects in diabetic (BMSC/DBM in DM group) and non-diabetic rats (BMSC/DBM in non-DM group), cell-free DBM scaffolds were implanted in diabetic rats to serve as the control group (DBM in DM group). X-ray, micro-CT and histological analyses were carried out to evaluate the bone regenerative potential of BMSC/DBM constructs under diabetic condition. In the rat subcutaneous implantation model, quantitative micro-CT analysis demonstrated that BMSC/DBM in DM group showed impaired bone regeneration activity compared with the BMSC/DBM in non-DM group (bone volume: 46 ± 4.4mm3 vs 58.9 ± 7.15mm3, *p < 0.05). In the rat femoral defect model, X-ray examination demonstrated that bone union was delayed in BMSC/DBM in DM group compared with BMSC/DBM in non-DM group. However, quantitative micro-CT analysis showed that after 6months of implantation, there was no significant difference in bone volume and bone density between the BMSC/DBM in DM group (199 ± 63mm3 and 593 ± 65mg HA/ccm) and the BMSC/DBM in non-DM group (211 ± 39mm3 and 608 ± 53mg HA/ccm). Our data suggested that BMSC/DBM constructs could repair large bone defects in diabetic rats, but with delayed healing process compared with non-diabetic rats. Our study suggest that biomaterial sacffolds seeded with allogenic fetal BMSCs represent a promising strategy to induce and improve bone regeneration under diabetic condition.

Bio-functional hydroxyapatite-coated 3D porous polyetherketoneketone scaffold for enhanced osteogenesis and osteointegration in orthopedic applications.

Polyetherketoneketone (PEKK), a high-performance thermoplastic special engineering material, maintains bone-like mechanical properties and has received considerable attention in the biomedical field. The 3D printing technique enables the production of porous scaffolds with a honeycomb structure featuring precisely controlled pore size, porosity and interconnectivity, which holds significant potential for applications in tissue engineering. The ideal pore architecture of porous PEKK scaffolds has yet to be elucidated. Porous PEKK scaffolds with five pore sizes P200 (225 ± 9.8 μm), P400 (411 ± 22.1 μm), P600 (596 ± 23.4 μm), P800 (786 ± 24.2 μm) and P1000 (993 ± 26.0 μm) were produced by a 3D printer. Subsequently, the optimum pore size, the P600, for mechanical properties and osteogenesis was selected based on in vitro experiments. To improve the interfacial bioactivity of porous PEKK scaffolds, hydroxyapatite (HAp) crystals were generated via in situ biomimetic mineralization induced by the phase-transited lysozyme coating. Herein, a micro/nanostructured surface showing HAp crystals on PEKK scaffold was developed. In vitro and in vivo experiments confirmed that the porous PEKK-HAp scaffolds exhibited highly interconnected pores and functional surface structures that were favorable for biocompatibility and osteoinductivity, which boosted bone regeneration. Therefore, this work not only demonstrates that the pore structure of the P600 scaffold is suitable for PEKK orthopedic implants but also sheds light on a synergistic approach involving 3D printing and biomimetic mineralization, which has the potential to yield customized 3D PEKK-HAp scaffolds with enhanced osteoinductivity and osteogenesis, offering a promising strategy for bone tissue engineering.

Extrusion 3D-printed tricalcium phosphate-polycaprolactone biocomposites for quercetin-KCl delivery in bone tissue engineering.

Critical-sized bone defects pose a significant challenge in advanced healthcare due to limited bone tissue regenerative capacity. The complex interplay of numerous overlapping variables hinders the development of multifunctional biocomposites. Phytochemicals show promise in promoting bone growth, but their dose-dependent nature and physicochemical properties halt clinical use. To develop a comprehensive solution, a 3D-printed (3DP) extrusion-based tricalcium phosphate-polycaprolactone (TCP-PCL) scaffold is augmented with quercetin and potassium chloride (KCl). This composite material demonstrates a compressive strength of 30 MPa showing promising stability for low load-bearing applications. Quercetin release from the scaffold follows a biphasic pattern that persists for up to 28 days, driven via diffusion-mediated kinetics. The incorporation of KCl allows for tunable degradation rates of scaffolds and prevents the initial rapid release. Functionalization of scaffolds facilitates the attachment and proliferation of human fetal osteoblasts (hfOB), resulting in a 2.1-fold increase in cell viability. Treated scaffolds exhibit a 3-fold reduction in osteosarcoma (MG-63) cell viability as compared to untreated substrates. Ruptured cell morphology and decreased mitochondrial membrane potential indicate the antitumorigenic potential. Scaffolds loaded with quercetin and quercetin-KCl (Q-KCl) demonstrate 76% and 89% reduction in bacterial colonies of Staphylococcus aureus, respectively. This study provides valuable insights as a promising strategy for bone tissue engineering (BTE) in orthopedic repair.

Multimaterial coextrusion (bio)printing of composite polymer biomaterial ink and hydrogel bioink for tissue fabrication

Bone tissue engineering strategies face considerable challenges owing to the complexity of the bone. This study introduces an unconventional method based on multimaterial 3D coextrusion-(bio)printing to address some of these challenges. The strategy enables simultaneous (bio)printing of a poly(lactic-co-glycolic acid)-based polymer ink laden with hydroxyapatite and a gelatin methacryloyl (GelMA)-based hydrogel bioink containing mesenchymal stem cells (MSCs). The resulting composite scaffolds exhibited a trabecular bone-like porosity and favorable compressive properties, surpassing those of GelMA alone. The (bio)printed MSCs demonstrated favorable viability, proliferation, morphology, and differentiation. This converged approach in multimaterial (bio)printing has the potential to transform the field of bone tissue engineering, offering a more efficient and effective way to regenerate skeletal tissues.

Stem Cells and Bone Tissue Engineering.

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair.

The Role of Vasculature and Angiogenic Strategies in Bone Regeneration.

Bone regeneration is a complex process that involves various growth factors, cell types, and extracellular matrix components. A crucial aspect of this process is the formation of a vascular network, which provides essential nutrients and oxygen and promotes osteogenesis by interacting with bone tissue. This review provides a comprehensive discussion of the critical role of vasculature in bone regeneration and the applications of angiogenic strategies, from conventional to cutting-edge methodologies. Recent research has shifted towards innovative bone tissue engineering strategies that integrate vascularized bone complexes, recognizing the significant role of vasculature in bone regeneration. The article begins by examining the role of angiogenesis in bone regeneration. It then introduces various in vitro and in vivo applications that have achieved accelerated bone regeneration through angiogenesis to highlight recent advances in bone tissue engineering. This review also identifies remaining challenges and outlines future directions for research in vascularized bone regeneration.

Computational models of bone fracture healing and applications: a review.

Fracture healing is a very complex physiological process involving multiple events at different temporal and spatial scales, such as cell migration and tissue differentiation, in which mechanical stimuli and biochemical factors assume key roles. With the continuous improvement of computer technology in recent years, computer models have provided excellent solutions for studying the complex process of bone healing. These models not only provide profound insights into the mechanisms of fracture healing, but also have important implications for clinical treatment strategies. In this review, we first provide an overview of research in the field of computational models of fracture healing based on CiteSpace software, followed by a summary of recent advances, and a discussion of the limitations of these models and future directions for improvement. Finally, we provide a systematic summary of the application of computational models of fracture healing in three areas: bone tissue engineering, fixator optimization and clinical treatment strategies. The application of computational models of bone healing in clinical treatment is immature, but an inevitable trend, and as these models become more refined, their role in guiding clinical treatment will become more prominent.

ELECTRICAL STIMULATION COMBINED WITH ADDITIVE MANUFACTURED 3D CONDUCTIVE SCAFFOLDS TOWARDS IMPROVED BONE-TISSUE ENGINEERING STRATEGIES

The growing number of non-union fractures in an aging population has increased the clinical demand for tissue-engineered bone. Electrical stimulation (ES) has been described as a promising strategy for bone regeneration treatments in several clinical studies. However the underlying mechanism by which ES augments bone formation is still poorly understood and its use in bone tissue engineering (BTE) strategies is currently underexplored. Additive manufacturing (AM) technologies (Fused Deposition Modeling/3D Printing) have been widely used in BTE due to their ability to fabricate scaffolds with a high control over their structural and mechanical properties in a reproducible and scalable manner. Thus, in this work, we combined AM methods with conductive biomaterials and ES to enhance the osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) envisaging improved BTE strategies.First, we started by developing AM-based electro-bioreactor devices containing medical-grade electrodes (stainless steel and Ti6Al4V) to apply ES to monolayer 2D cultures and 3D cell-seeded scaffolds. Computer modeling(Finite Element Analysis-FEA) was employed to predict the magnitude/distribution of electrical fields within the ES devices and along the different conductive scaffolds. Prior to scaffold culture, 5 different ES protocols were tested in terms of their ability to promote hBMSCs proliferation and osteogenic differentiation in 2D cultures. The best performance ES protocol was then used in two different AM-based BTE strategies: 1) Two different conductive scaffolds (conductive poly lactic acid (PLA) and titanium) were seeded with hBMSCs and cultured for 21 days under osteogenic medium conditions with and without ES and their biological performance was evaluated in comparison to non-conductive standard PLA scaffolds; 2) Different PEDOT:PSS-based coating solutions were screened to obtain PEDOT:PSS/Gelatin-coated 3D polycaprolactone (PCL) scaffolds with a high(11 S.cm-1) and stable electroconductivity. When cultured under ES, PEDOT:PSS/Gelatin-PCL scaffolds enhanced significantly hBMSCs osteogenic differentiation and mineralization(calcium deposition), highlighting their potential for BTE applications.Acknowledgements: Funding received from FCT through projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), and to the institutions iBB (UIDB/04565/2020), CDRSP (UIDB/04044/2020) and Associate Laboratory i4HB (LA/P/0140/2020).

NOVEL MINERALIZED ELECTROACTIVE PAN/PEDOT:PSS NANOFIBERS FOR BONE TISSUE ENGINEERING

Bone defects can result from different incidents such as acute trauma, infection or tumor resection. While in most instances bone healing can be achieved given the tissue's innate ability of self-repair, for critical-sized defects spontaneous regeneration is less likely to occur, therefore requiring surgical intervention. Current clinical procedures have failed to adequately address this issue. For this reason, bone tissue engineering (BTE) strategies involving the use of synthetic grafts for replacing damaged bone and promoting the tissue's regeneration are being investigated. The electrical stimulation (ES) of bone defects using direct current has yielded very promising results, with neo tissue formation being achieved in the target sites in vivo. Electroactive implantable scaffolds comprised by conductive biomaterials could be used to assist this kind of therapy by either directing the ES specifically to the damaged site or promoting the integration of electrodes within the bone tissue as a coating. In this study, we developed novel conductive heat-treated polyacrylonitrile/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PAN/PEDOT:PSS) nanofibers via electrospinning capable of mimicking key native features of the bone tissue's extracellular matrix (ECM) and providing a platform for the delivery of exogenous ES. The developed scaffolds were doped with sulfuric acid and mineralized in Simulated Body Fluid to mimic the inorganic phase of bone ECM. As expected, the doped PAN/PEDOT:PSS nanofibers exhibited electroconductive properties and were able to preserve their fibrous structure. The addition of PEDOT:PSS was found to improve the bioactivity of the scaffolds, with a more significant in vitro mineralization being obtained. By seeding the scaffolds with MG-63 osteoblasts and human mesenchymal stem/stromal cells, an increased cell proliferation was observed for the mineralized PAN/PEDOT:PSS nanofibers, which also registered an increased expression of key osteogenic markers (e.g Osteopontin). Our findings appear to corroborate the promising potential of the generated nanofibers for future ES-based BTE applications.Acknowledgements: The authors thank FCT for funding through the projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), BioMaterARISES (EXPL/CTM-CTM/0995/2021) and OptiBioScaffold (PTDC/EME-SIS/32554/2017, POCI-01- 0145-FEDER- 32554), the PhD scholarship (2022.10572.BD) and through institutional funding to iBB (UIDB/04565/2020 and UIDP/04565/2020), Associate Laboratory i4HB (LA/P/0140/2020) and IT (UIDB/50008/2020).

Synergy between 3D-extruded electroconductive scaffolds and electrical stimulation to improve bone tissue engineering strategies.

In this work, we propose a simple, reliable, and versatile strategy to create 3D electroconductive scaffolds suitable for bone tissue engineering (TE) applications with electrical stimulation (ES). The proposed scaffolds are made of 3D-extruded poly(ε-caprolactone) (PCL), subjected to alkaline treatment, and of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), anchored to PCL with one of two different crosslinkers: (3-glycidyloxypropyl)trimethoxysilane (GOPS) and divinyl sulfone (DVS). Both cross-linkers allowed the formation of a homogenous and continuous coating of PEDOT:PSS to PCL. We show that these PEDOT:PSS coatings are electroconductive (11.3-20.1 S cm-1), stable (up to 21 days in saline solution), and allow the immobilization of gelatin (Gel) to further improve bioactivity. In vitro mineralization of the corresponding 3D conductive scaffolds was greatly enhanced (GOPS(NaOH)-Gel - 3.1 fold, DVS(NaOH)-Gel - 2.0 fold) and cell colonization and proliferation were the highest for the DVS(NaOH)-Gel scaffold. In silico modelling of ES application in DVS(NaOH)-Gel scaffolds indicates that the electrical field distribution is homogeneous, which reduces the probability of formation of faradaic products. Osteogenic differentiation of human bone marrow derived mesenchymal stem/stromal cells (hBM-MSCs) was performed under ES. Importantly, our results clearly demonstrated a synergistic effect of scaffold electroconductivity and ES on the enhancement of MSC osteogenic differentiation, particularly on cell-secreted calcium deposition and the upregulation of osteogenic gene markers such as COL I, OC and CACNA1C. These scaffolds hold promise for future clinical applications, including manufacturing of personalized bone TE grafts for transplantation with enhanced maturation/functionality or bioelectronic devices.

Chitosan‐gelatin/hydroxyapatite‐based scaffold associated with mesenchymal stem cells differentiate into osteoblasts improves the surface of the bone lesion in mice C57BL/6J

AbstractExtensive injuries to bone tissue are still considered a significant clinical challenge; therefore, developing new bone tissue engineering (BTE) strategies is still necessary. This work aims to construct and characterize a chitosan‐gelatin/hydroxyapatite‐based (CG/H) scaffold to provide well‐design support for mesenchymal stem cell (MSC) growth and differentiation to osteoblasts. First, the CG/H scaffolds are construct by freeze‐drying. Then, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, x‐ray diffraction, water uptake, and degradation profiles evaluate the material's surface. In addition, the CG/H morphological, biochemical, and MSC adhesion processes and growth behavior are also assess, indicating reasonable adhesion rates to the surface, low material cytotoxicity, and excellent alkaline phosphatase activity compared to control on the cellular framework. Based on these results, we obtain a highly biocompatible scaffold and that can support osteoblast differentiation. Finally, the in vivo studies demonstrate the CG/H scaffold with MSC adhere is capable of differentiating into osteoblasts, and the application of this scaffold is able to significantly enhance the closure of the bone lesion. Therefore, the CG/H scaffold has potential clinical application for bone regeneration.

Hydrothermal synthesis of valve metal Zr-doped titanate nanofibers for bone tissue engineering

Investigations are underway to identify novel biomaterials to improve strategies for bone tissue engineering. Hybrid nanomaterials have emerged as a viable class of biomaterials. Here, we report a facile, economical, optimized, and well-controlled hydrothermal method for synthesizing Zr-doped potassium titanate nanofibers with high purity. Upon morphological characterization, Zr-doping did not disrupt the parent crystal structure of potassium titanate, which showed huge potential for bone tissue engineering.

Bone repair potential of collagen-poly(3-hydroxybutyrate)-carbon nanotubes scaffold loaded with mesenchymal stem cells for the reconstruction of critical-sized mandibular defects

The poor structural stability of collagen (COL) upon hydration poses a significant challenge in tissue engineering (TE). To overcome this limitation, the incorporation of hydrophobic polymers such as poly(3-hydroxybutyrate) (PHB), and nanomaterials such as carbon nanotubes (CNTs) has been explored. In this study, we investigated the physical, chemical, and biological characteristics of COL-based scaffolds modified with PHB and CNTs for bone tissue engineering (BTE) applications. The tensile strength analysis revealed a substantial improvement in the ultimate tensile strength with the addition of 10 % PHB and 4 % CNTs. Scanning electron microscopy (SEM) images depicted a denser and more compact structure resulting from the presence of PHB and CNTs, enhancing the scaffold's mechanical properties. Fourier-transform infrared spectroscopy (FTIR) confirmed the successful incorporation of PHB and CNTs into the composite scaffold, maintaining the chemical integrity of COL. Stereological studies also conducted in a rat model with induced critical-sized bone defects in the mandibular bone further emphasize the substantial increase in bone formation and reduction in defect volume achieved by the scaffold loaded with stem cells. These findings underscore the promising approach to enhance bone healing, using COL-based scaffolds loaded with stem cells, and the favorable results obtained in this study can contribute to the advancement of BTE strategies.

β-TCP from 3D-printed composite scaffolds acts as an effective phosphate source during osteogenic differentiation of human mesenchymal stromal cells.

Introduction: Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are often combined with calcium phosphate (CaP)-based 3D-printed scaffolds with the goal of creating a bone substitute that can repair segmental bone defects. In vitro, the induction of osteogenic differentiation traditionally requires, among other supplements, the addition of β-glycerophosphate (BGP), which acts as a phosphate source. The aim of this study is to investigate whether phosphate contained within the 3D-printed scaffolds can effectively be used as a phosphate source during hBM-MSC in vitro osteogenesis. Methods: hBM-MSCs are cultured on 3D-printed discs composed of poly (lactic-co-glycolic acid) (PLGA) and β-tricalcium phosphate (β-TCP) for 28 days under osteogenic conditions, with and without the supplementation of BGP. The effects of BGP removal on various cellular parameters, including cell metabolic activity, alkaline phosphatase (ALP) presence and activity, proliferation, osteogenic gene expression, levels of free phosphate in the media and mineralisation, are assessed. Results: The removal of exogenous BGP increases cell metabolic activity, ALP activity, proliferation, and gene expression of matrix-related (COL1A1, IBSP, SPP1), transcriptional (SP7, RUNX2/SOX9, PPARγ) and phosphate-related (ALPL, ENPP1, ANKH, PHOSPHO1) markers in a donor dependent manner. BGP removal leads to decreased free phosphate concentration in the media and maintained of mineral deposition staining. Discussion: Our findings demonstrate the detrimental impact of exogenous BGP on hBM-MSCs cultured on a phosphate-based material and propose β-TCP embedded within 3D-printed scaffold as a sufficient phosphate source for hBM-MSCs during osteogenesis. The presented study provides novel insights into the interaction of hBM-MSCs with 3D-printed CaP based materials, an essential aspect for the advancement of bone tissue engineering strategies aimed at repairing segmental defects.

Dual-response of multi-functional microsphere system to ultrasound and microenvironment for enhanced bone defect treatment

Using bone tissue engineering strategies to achieve bone defect repair is a promising modality. However, the repair process outcomes are often unsatisfactory. Here we properly designed a multi-functional microsphere system, which could deliver bioactive proteins under the dual response of ultrasound and microenvironment, release microenvironment-responsive products on demand, reverse bone injury microenvironment, regulate the immune microenvironment, and achieve excellent bone defect treatment outcomes. In particular, the MnO2 introduced into the poly(lactic-co-glycolic acid) (PLGA) microspheres during synthesis could consume the acid produced by the degradation of PLGA to protect bone morphogenetic protein-2 (BMP-2). More importantly, MnO2 could consume reactive oxygen species (ROS) and produce Mn2+ and oxygen (O2), further promoting the repair of bone defects while reversing the microenvironment. Moreover, the reversal of the bone injury microenvironment and the depletion of ROS promoted the polarization of M1 macrophages to M2 macrophages, and the immune microenvironment was regulated. Notably, the ultrasound (US) irradiation used during treatment also allowed the on-demand release of microenvironment-responsive products. The multi-functional microsphere system combines the effects of on-demand delivery, reversal of bone injury microenvironment, and regulation of the immune microenvironment, providing new horizons for the clinical application of protein delivery and bone defect repair.

Microenvironment-targeted strategy steers advanced bone regeneration.

Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Traditional strategies in bone tissue engineering have focused primarily on mimicking the extracellular matrix (ECM) of bone in terms of structure and composition. However, the synergistic effects of other cues from the microenvironment during bone regeneration are often neglected. The bone microenvironment is a sophisticated system that includes physiological (e.g., neighboring cells such as macrophages), chemical (e.g., oxygen, pH), and physical factors (e.g., mechanics, acoustics) that dynamically interact with each other. Microenvironment-targeted strategies are increasingly recognized as crucial for successful bone regeneration and offer promising solutions for advancing bone tissue engineering. This review provides a comprehensive overview of current microenvironment-targeted strategies and challenges for bone regeneration and further outlines prospective directions of the approaches in construction of bone organoids.

A microfluidic organ-on-a-chip: into the next decade of bone tissue engineering applied in dentistry.

A comprehensive understanding of the complex physiological and pathological processes associated with alveolar bones, their responses to different therapeutics strategies, and cell interactions with biomaterial becomes necessary in precisely treating patients with severe progressive periodontitis, as a bone-related issue in dentistry. However, existing monolayer cell culture or pre-clinical models have been unable to mimic the complex physiological, pathologicaland regeneration processes in the bone microenvironment in response to different therapeutic strategies. In this point, 'organ-on-a-chip' (OOAC) technology, specifically 'alveolar-bone-on-a-chip', is expected to resolve the problems by better imitating infection site microenvironment and microphysiology within the oral tissues. The OOAC technology is assessed in this study toward better approaches in disease modeling and better therapeutics strategy for bone tissue engineering applied in dentistry.

Self‐Adaptive MoO3−x Subnanometric Wires Incorporated Scaffolds for Osteosarcoma Therapy and Bone Regeneration

AbstractResidual tumor cells and bone tissue defects are two critical challenges in clinical osteosarcoma treatment. Herein, a subnanomedicine concept is proposed by developing a self‐adaptive functional tissue engineering scaffold constructed by integrating MoO3−x subnanometric wires onto 3D printing bioactive glass scaffolds. The MoO3−x subnanometric wires are synthesized by a one‐pot hydrothermal method, which aggregate in an acidic tumor microenvironment and react with hydrogen peroxide to produce reactive oxygen species for specific chemodynamic therapy. However, they can degrade rapidly under physiological conditions without causing toxicity. Moreover, self‐adaptively enhanced photothermal conversion enables tumor‐targeting photothermal therapy while enhancing chemodynamic therapy. Additionally, the Mo5+‐Mo6+ transition enables lipid peroxide accumulation and glutathione depletion, thereby resulting in the deactivation of glutathione peroxidase 4 protein and ferroptosis through Western blot analysis, confocal laser scanning microscopy observation, and mRNA transcriptome analysis. In addition to its robustness against osteosarcoma, the constructed scaffolds can stimulate rat bone mesenchymal stem cell differentiation and proliferation as well as promote osteogenesis in bone defects. Therefore, this multifunctional scaffold not only validates the subnanomedicine concept but also provides a promising clinical strategy for bone tissue engineering.

Advances in new materials for bone tissue engineering simplifying postoperative rehabilitation: Recent Scientific Breakthroughs

Introduction: Bone tissue engineering has emerged as a promising field in regenerative medicine, aiming to develop innovative materials and approaches for bone repair and regeneration, which also leads to the simplification and search for new approaches in postoperative rehabilitation. The integration of novel materials into scaffolds and implants plays a crucial role in improving bone tissue engineering strategies. In recent years, scientific research has made significant progress in identifying and characterizing novel materials with superior properties and functionalities.&#x0D; Aim: This article explores the most recent scientific findings and research breakthroughs concerning novel materials for bone tissues, focusing on their biocompatibility, mechanical properties, bioactivity, and potential clinical applications.&#x0D; Conclusion: In recent years, the field of bone tissue engineering has witnessed remarkable advancements in the development of novel materials for bone repair and regeneration, which also simplify the medical rehabilitation of the patient. From bioactive glasses and calcium phosphate-based materials to biodegradable magnesium-based materials and graphene-based composites, researchers have explored a wide range of materials with diverse properties and functionalities. As the field continues to evolve, the integration of cutting-edge technologies, such as 3D printing and nanotechnology, is expected to further enhance the efficacy and clinical relevance of these novel materials, ultimately benefiting patients with bone defects and diseases.

Matrix stiffness regulates osteoclast fate through integrin-dependent mechanotransduction.

Osteoclasts ubiquitously participate in bone homeostasis, and their aberration leads to bone diseases, such as osteoporosis. Current clinical strategies by biochemical signaling molecules often perturb innate bone metabolism owing to the uncontrolled management of osteoclasts. Thus, an alternative strategy of precise regulation for osteoclast differentiation is urgently needed. To this end, this study proposed an assumption that mechanic stimulation might be a potential strategy. Here, a hydrogel was created to imitate the physiological bone microenvironment, with stiffnesses ranging from 2.43kPa to 68.2kPa. The impact of matrix stiffness on osteoclast behaviors was thoroughly investigated. Results showed that matrix stiffness could be harnessed for directing osteoclast fate in vitro and in vivo. In particular, increased matrix stiffness inhibited the integrin β3-responsive RhoA-ROCK2-YAP-related mechanotransduction and promoted osteoclastogenesis. Notably, preosteoclast development is facilitated by medium-stiffness hydrogel (M-gel) possessing the same stiffness as vessel ranging from 17.5kPa to 44.6kPa by partial suppression of mechanotransduction, which subsequently encouraged revascularization and bone regeneration in mice with bone defects. Our works provide an innovative approach for finely regulating osteoclast differentiation by selecting the optimum matrix stiffness and enable us further to develop a matrix stiffness-based strategy for bone tissue engineering.