A biomimetic piezoelectric scaffold with sustained Mg2+ release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration

Bioactive Materials, Год журнала: 2022, Номер 25, С. 399 - 414

Опубликована: Ноя. 29, 2022

Natural bone is a composite tissue made of organic and inorganic components, showing piezoelectricity. Whitlockite (WH), which natural magnesium-containing calcium phosphate, has attracted great attention in formation recently due to its unique piezoelectric property after sintering treatment sustained release magnesium ion (Mg2+). Herein, scaffold (denoted as PWH scaffold) composed WH (PWH) poly(ε-caprolactone) (PCL) was 3D printed meet the physiological demands for regeneration neuro-vascularized tissue, namely, providing endogenous electric field at defect site. The Mg2+ from scaffold, displaying multiple biological activities, thus exhibits strong synergistic effect with piezoelectricity on inhibiting osteoclast activation, promoting neurogenic, angiogenic, osteogenic differentiation marrow mesenchymal stromal cells (BMSCs) vitro. In rat calvarial model, this remarkably conducive efficient neo-bone rich neurogenic angiogenic expressions. Overall, study presents first example biomimetic vivo, offers new insights regenerative medicine.

Язык: Английский

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Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration

ACS Nano, Год журнала: 2024, Номер 18(10), С. 7504 - 7520

Опубликована: Фев. 27, 2024

The essential role of the neural network in enhancing bone regeneration has often been overlooked biomaterial design, leading to delayed or compromised healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs stimulated with nerve growth factor (NGF) regulate exosomal cargoes improve neuro-promotive potential facilitate innervated regeneration. In vitro cell experiments showed that NGF-stimulated MSCs-derived (N-Exos) obviously improved function neurotrophic effects cells, consequently, osteogenic osteo-reparative cells. Bioinformatic analysis by miRNA sequencing pathway enrichment revealed beneficial N-Exos may partly be ascribed NGF-elicited multicomponent miRNAs subsequent regulation activation MAPK PI3K-Akt signaling pathways. On this basis, were delivered on micropores 3D-printed hierarchical porous scaffold accomplish sustained release profile extended bioavailability. a rat model distal femoral defect, N-Exos-functionalized significantly induced neurovascular structure formation This study provided feasible strategy modulate functional acquire desirable potential. Furthermore, developed represent promising neurovascular-promotive reparative clinical translation.

Язык: Английский

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Novel “Hot Spring”-Mimetic Scaffolds for Sequential Neurovascular Network Reconstruction and Osteoporosis Reversion

Biomaterials, Год журнала: 2025, Номер 320, С. 123191 - 123191

Опубликована: Фев. 18, 2025

Язык: Английский

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Strategies for promoting neurovascularization in bone regeneration

Military Medical Research, Год журнала: 2025, Номер 12(1)

Опубликована: Март 3, 2025

Abstract Bone tissue relies on the intricate interplay between blood vessels and nerve fibers, both are essential for many physiological pathological processes of skeletal system. Blood provide necessary oxygen nutrients to bone tissues, remove metabolic waste. Concomitantly, fibers precede during growth, promote vascularization, influence cells by secreting neurotransmitters stimulate osteogenesis. Despite critical roles components, current biomaterials generally focus enhancing intraosseous vessel repair, while often neglecting contribution nerves. Understanding distribution main functions in is crucial developing effective engineering. This review first explores anatomy highlighting their vital embryonic development, metabolism, repair. It covers innovative regeneration strategies directed at accelerating intrabony neurovascular system over past 10 years. The issues covered included material properties (stiffness, surface topography, pore structures, conductivity, piezoelectricity) acellular biological factors [neurotrophins, peptides, ribonucleic acids (RNAs), inorganic ions, exosomes]. Major challenges encountered neurovascularized materials clinical translation have also been highlighted. Furthermore, discusses future research directions potential developments aimed producing repair that more accurately mimic natural healing tissue. will serve as a valuable reference researchers clinicians novel into practice. By bridging gap experimental practical application, these advancements transform treatment defects significantly improve quality life patients with bone-related conditions.

Язык: Английский

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Versatile application of magnesium-related bone implants in the treatment of bone defects

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101635 - 101635

Опубликована: Март 5, 2025

Magnesium-related bone implants have garnered significant attention in the treatment of defects. The applications magnesium promoting repair mainly include degradable magnesium-based scaffolds owing to its special physical properties and composite materials modified by ions because biological activity. Although numerous studies confirmed unique application advantages efficacy repair, some obvious shortcomings persist, including rapid degradation scaffolds. In this review, deficiencies alloys construction orthopedic their key influencing factors were summarized; furthermore, advanced improvement schemes summarized analyzed. Additionally, strategies magnesium-modified are discussed. Lastly, review incorporates latest research discoveries on science, comprehensively exploring mechanism magnesium's role complex microenvironment defects from multiple dimensions. This paper provides a comprehensive summary analysis cutting-edge concepts design development implants, considering various perspectives such as functions magnesium.

Язык: Английский

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Topography-mediated immunomodulation in osseointegration; Ally or Enemy

Biomaterials, Год журнала: 2022, Номер 291, С. 121903 - 121903

Опубликована: Ноя. 9, 2022

Язык: Английский

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A multifunctional neuromodulation platform utilizing Schwann cell-derived exosomes orchestrates bone microenvironment via immunomodulation, angiogenesis and osteogenesis

Bioactive Materials, Год журнала: 2022, Номер 23, С. 206 - 222

Опубликована: Ноя. 14, 2022

Recent evidence highlights multifaceted biological needs to recapitulate the bone microenvironment for regeneration. Neurotization has great potential realizing multi-system modulations in tissue engineering (BTE). However, a neural strategy involving all key repair steps temporally not yet been reported. In this study, we reported hydrogel-encapsulated Schwann cell-derived exosomes (SC Exo). This sustained-release SC Exo system prominently enhanced regeneration by promoting innervation, immunoregulation, vascularization, and osteogenesis vivo. Moreover, vitro results further confirmed that significantly induced M2 polarization of macrophages, tube formation HUVECs, BMSCs osteogenic differentiation. Furthermore, was promoted upregulating TGF-β1/SMAD2/3 signaling pathway. summary, novel cell-free easily prepared successfully developed promote orchestrating entire healing microenvironment, which may provide new clinical treatment defects.

Язык: Английский

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Neuro–bone tissue engineering: emerging mechanisms, potential strategies, and current challenges

Bone Research, Год журнала: 2023, Номер 11(1)

Опубликована: Дек. 20, 2023

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral endings release neurogenic factors and sense signals, mediate bone metabolism pain. In recent years, tissue engineering has increasingly focused on the effects of nervous system regeneration. Simultaneous regeneration nerves through use materials or by enhancement endogenous repair signals been proven to promote functional Additionally, emerging information mechanisms interoception central regulation homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews this topic are lacking. Therefore, review provides overview relationship between regeneration, focusing applications. We discuss novel regulatory explore innovative approaches based nerve-bone interactions Finally, challenges future prospects field briefly discussed.

Язык: Английский

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Copper Ion‐Modified Germanium Phosphorus Nanosheets Integrated with an Electroactive and Biodegradable Hydrogel for Neuro‐Vascularized Bone Regeneration

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(27)

Опубликована: Июль 8, 2023

Severe bone defects accompanied by vascular and peripheral nerve injuries represent a huge orthopedic challenge are often the risk of infection. Thus, biomaterials with antibacterial neurovascular regeneration properties highly desirable. Here, newly designed biohybrid biodegradable hydrogel (GelMA) containing copper ion-modified germanium-phosphorus (GeP) nanosheets, which act as neuro-vascular agents, is designed. The ion modification process serves to improve stability GeP nanosheets offers platform for sustained release bioactive ions. Study findings show that GelMA/GeP@Cu has effective properties. integrated can significantly boost osteogenic differentiation marrow mesenchymal stem cells, facilitate angiogenesis in human umbilical vein endothelial up-regulate neural differentiation-related proteins cells vitro. In vivo, rat calvarial defect mode, found enhance neurogenesis, eventually contributing regeneration. These indicate field tissue engineering, serve valuable biomaterial neuro-vascularized infection prevention.

Язык: Английский

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Zinc based biodegradable metals for bone repair and regeneration: Bioactivity and molecular mechanisms

Materials Today Bio, Год журнала: 2023, Номер 25, С. 100932 - 100932

Опубликована: Дек. 28, 2023

Bone fractures and critical-size bone defects are significant public health issues, clinical treatment outcomes closely related to the intrinsic properties of utilized implant materials. Zinc (Zn)-based biodegradable metals (BMs) have emerged as promising bioactive materials because their exceptional biocompatibility, appropriate mechanical properties, controllable biodegradation. This review summarizes state art in terms Zn-based for repair regeneration, focusing on bridging gap between biological mechanism required bioactivity. The molecular underlying release Zn ions from BMs improvement regeneration is elucidated. By integrating considerations specific bioactivity materials, this current research status internal fixation promoting fracture healing, scaffolds regenerating defects, barrier membranes reconstituting alveolar defects. Considering progress made potential applications, challenges directions proposed discussed.

Язык: Английский

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