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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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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Effects of Electric Field‐Modulated Conductive Hydrogel on Osseoperception and Osseointegration of Dental Implants

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(28)

Published: March 14, 2024

Abstract Achieving optimal implant restoration hinges on both robust osseointegration as the structural foundation and favorable osseoperception for advanced masticatory function. The significance of nerve innervation in peri‐implant environment cornerstone is often underestimated. Despite integral role endogenous electric fields (EFs) human body, particularly electrosensitive tissues like tissue, current approach involving external electrical stimulation invasive not clinically applicable. present study introduces a conductive hydrogel designed to respond EFs, aiming foster regeneration around dental implants coordinate osseoperception. promotes neurite outgrowth by upregulating intracellular Ca 2+ concentration activating subsequent pathways. Furthermore, enhanced release neuropeptides from neurocells improves osteogenesis osteoblasts. impact also thoroughly investigated vivo. This represents unique strategy enhancing within EFs environment. advancement opens door achieving physiological psychological integration implants.

Language: Английский

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Strategies for promoting neurovascularization in bone regeneration

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: March 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.

Language: Английский

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Cell communication and relevant signaling pathways in osteogenesis–angiogenesis coupling

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: April 7, 2025

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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Synergistic large segmental bone repair by 3D printed bionic scaffolds and engineered ADSC nanovesicles: Towards an optimized regenerative microenvironment

Biomaterials, Journal Year: 2024, Volume and Issue: 308, P. 122566 - 122566

Published: April 8, 2024

Achieving sufficient bone regeneration in large segmental defects is challenging, with the structure of repair scaffolds and their loaded bioactive substances crucial for modulating local osteogenic microenvironment. This study utilized digital laser processing (DLP)-based 3D printing technology to successfully fabricate high-precision methacryloylated polycaprolactone (PCLMA) bionic scaffold structures. Adipose-derived stem cell-engineered nanovesicles (ADSC-ENs) were uniformly stably modified onto surface using a perfusion device, constructing conducive microenvironment tissue long defect through scaffold's structural design vesicles' biological functions. Scanning electron microscopy (SEM) examination confirmed efficient loading ADSC-ENs. The material group vesicles (PCLMA-BAS-ENs) demonstrated good cell compatibility potential when analyzed adhesion osteogenesis primary rabbit marrow mesenchymal cells (BMSCs) on surface. Tested 15 mm critical radial model, PCLMA-BAS-ENs facilitated near-complete after 12 weeks. Immunofluorescence proteomic results indicated that significantly improved at site vivo, promoted angiogenesis, enhanced polarization macrophages towards M2 phenotype, recruitment BMSCs. Thus, was proven promote defects. Overall, this strategy combining engineered highly biomimetic large-segment holds great orthopedic other regenerative medicine applications.

Language: Английский

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Innovative Biomaterials for Bone Tumor Treatment and Regeneration: Tackling Postoperative Challenges and Charting the Path Forward

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(16)

Published: March 2, 2024

Abstract Surgical resection of bone tumors is the primary approach employed in treatment cancer. Simultaneously, perioperative interventions, particularly postoperative adjuvant anticancer strategies, play a crucial role achieving satisfactory therapeutic outcomes. However, occurrence tumor recurrence, metastasis, extensive defects, and infection are significant risks that can result unfavorable prognoses or even failure. In recent years, there has been progress development biomaterials, leading to emergence new options for therapy regeneration. This report aims comprehensively analyze strategic unique biomaterials with inherent healing properties bioactive capabilities tissue These composite classified into metallic, inorganic non‐metallic, organic types, thoroughly investigated their responses external stimuli such as light magnetic fields, internal interventions including chemotherapy catalytic therapy, combination well Additionally, an overview self‐healing materials osteogenesis provided potential applications combating osteosarcoma promoting formation explored. Furthermore, safety concerns integrated current limitations addressed, while also discussing challenges future prospects.

Language: Английский

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Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis

Molecules, Journal Year: 2024, Volume and Issue: 29(9), P. 2050 - 2050

Published: April 29, 2024

Deferoxamine, an iron chelator used to treat diseases caused by excess iron, has had a Food and Drug Administration-approved status for many years. A large number of studies have confirmed that deferoxamine can reduce inflammatory response promote angiogenesis. Blood vessels play crucial role in sustaining vital life facilitating the delivery immune cells, oxygen, nutrients, as well eliminating waste products generated during cellular metabolism. Dysfunction blood may contribute significantly development life-threatening diseases. Anti-angiogenesis therapy pro-angiogenesis/angiogenesis strategies been frequently recommended various Herein, we describe mechanism which promotes angiogenesis summarize its application chronic wounds, bone repair, respiratory system. Furthermore, discuss drug system treating diseases, providing constructive ideas inspiration new treatment strategies.

Language: Английский

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Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant transformation should not be ignored. Compared to stem implantation, recruitment endogenous cells injured sites is more critical in situ regeneration. In this study, based on the acidic microenvironment injury, an HG‐AA 1:1 ‐SDF‐1α composite hydrogel with a dual‐control intelligent switch function developed by incorporating stromal cell‐derived factor (SDF‐1α), arginine carbon dots (Arg‐CDs), calcium ions (Ca 2+ ) into oxidized hyaluronic acid/gelatin methacryloyl (HG) hydrogel. The triggers first (Schiff base bond broken between SDF‐1α) continuously release SDF‐1α. neutral (pH 7.4) media, cumulative SDF‐1α 5.5) media ≈2.5 times higher, which enhances migration mesenchymal (MSCs). recruited MSCs immediately initiate second metabolize Arg‐CDs bioactive nitric oxide (NO) presence Ca , activating NO/cyclic guanosine monophosphate (cGMP) signaling pathway promote angiogenesis. Therefore, engineered shows promising potential achieve “coupling osteogenesis angiogenesis”

Language: Английский

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