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

Bioactive Materials, Journal Year: 2022, Volume and Issue: 25, P. 399 - 414

Published: Nov. 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.

Language: 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, Journal Year: 2024, Volume and Issue: 18(10), P. 7504 - 7520

Published: Feb. 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.

Language: Английский

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

Bioactive Materials, Journal Year: 2022, Volume and Issue: 23, P. 206 - 222

Published: Nov. 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.

Language: Английский

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Topography-mediated immunomodulation in osseointegration; Ally or Enemy

Biomaterials, Journal Year: 2022, Volume and Issue: 291, P. 121903 - 121903

Published: Nov. 9, 2022

Language: Английский

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

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Dec. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 12(27)

Published: July 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.

Language: Английский

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Bioprinted Scaffold Remodels the Neuromodulatory Microenvironment for Enhancing Bone Regeneration

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(40)

Published: May 31, 2023

Abstract Herein, a 3D bioprinted scaffold is proposed, containing calcitonin gene‐related peptide (CGRP) and the β ‐adrenergic receptor blocker propranolol (PRN) as new method to achieve effective repair of bone defects. By leveraging neuromodulation mechanism regeneration, CGRP PRN loaded mesoporous silica nanoparticles are added into hybrid bio‐ink, which initially contains gelatin methacrylate, Poly (ethylene glycol) diacrylate marrow mesenchymal stem cells (BMSCs). Subsequently, optimized bio‐ink used for bioprinting create composite with pre‐designed micro‐nano hierarchical structure. The migration tube formation human umbilical vein endothelial (HUVECs) can be promoted by scaffold, beneficial capillary network during process. With release from secretion neuropeptides sensory nerves simulated. Meanwhile, inhibit binding process catecholamine receptor, co‐promoting osteogenic differentiation BMSCs silicon ions, will effectively enhance critical‐sized cranial defect in rat model. In conclusion, this study provides promising strategy understanding neuromodulatory mechanisms regeneration.

Language: Английский

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

Materials Today Bio, Journal Year: 2023, Volume and Issue: 25, P. 100932 - 100932

Published: Dec. 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.

Language: Английский

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Crosstalk Between the Neuroendocrine System and Bone Homeostasis

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 45(1), P. 95 - 124

Published: July 17, 2023

Abstract The homeostasis of bone microenvironment is the foundation health and comprises 2 concerted events: formation by osteoblasts resorption osteoclasts. In early 21st century, leptin, an adipocytes-derived hormone, was found to affect through hypothalamic relay sympathetic nervous system, involving neurotransmitters like serotonin norepinephrine. This discovery has provided a new perspective regarding synergistic effects endocrine systems on skeletal homeostasis. Since then, more studies have been conducted, gradually uncovering complex neuroendocrine regulation underlying Intriguingly, also considered as organ that can produce regulatory factors in turn exert activities. After decades exploration into mechanisms, separate bioactive extensively investigated, whereas few systematically shown global view regulation. Therefore, we summarized previously studied patterns from system bone. review will provide readers with panoramic intimate relationship between bone, compensating for current understanding homeostasis, probably developing therapeutic strategies its related disorders.

Language: Английский

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Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(13), P. 4385 - 4385

Published: June 29, 2023

Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, traumatic fractures require effective treatments that favor bone formation regeneration. Among these, cell therapy based on mesenchymal cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part paracrine properties. These mainly mediated extracellular vesicle (EV) secretion. EV modulates processes inflammation, angiogenesis, proliferation, migration, differentiation. Thus, MSC-EV currently an important tool for the development of cell-free therapies medicine. This review describes current knowledge effects different phases used intravenous injection, directly or combination with types biomaterials, preclinical models diseases. They have shown great clinical potential medicine applied to bone. findings should be confirmed through standardization protocols, a better understanding mechanisms action, appropriate trials. All will allow translation human clinic applications.

Language: Английский

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