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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Neurovascularization inhibiting dual responsive hydrogel for alleviating the progression of osteoarthritis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 6, 2025

Abstract Treating osteoarthritis (OA) associated pain is a challenge with the potential to significantly improve patients lives. Here, we report on hydrogel for extracellular RNA scavenging and releasing bevacizumab block neurovascularization at osteochondral interface, thereby mitigating OA disease progression. The formed by cross-linking aldehyde-phenylboronic acid-modified sodium alginate/polyethyleneimine-grafted protocatechuic acid (OSAP/PPCA) sustained-release nanoparticles (BGN@Be), termed OSPPB. dynamic Schiff base bonds boronic ester allow injectability, self-healing, pH/reactive oxygen species dual responsiveness. OSPPB can inhibit angiogenesis neurogenesis in vitro. In an vivo model, intraarticular injection of accelerates healing process condyles alleviates chronic inhibiting interface. injectable represents promising technique treat pain.

Язык: Английский

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Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 5, 2023

Abstract Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that central nervous system (CNS) plays a pivotal role in regulating immune and skeletal homeostasis. However, impact of CNS on hematopoiesis commitment was overlooked. Here, we found dramatically elevated sympathetic tone accompanied with TBI-accelerated healing; chemical sympathectomy blocks TBI-induced healing. hypersensitivity adrenergic signaling promotes proliferation bone marrow hematopoietic stem cells (HSCs) swiftly skews HSCs toward anti-inflammation myeloid within 14 days, which favor Knockout β3- or β2-adrenergic receptor (AR) eliminate TBI-mediated macrophage expansion RNA sequencing revealed Adrb2 Adrb3 maintain cells. Importantly, flow cytometry confirmed deletion β2-AR inhibits M2 polarization macrophages at 7th day 14th day; impaired β3-AR knockout mice. Moreover, agonists synergistically promote infiltration callus accelerate healing process. Thus, conclude TBI formation during early stage process by shaping environment marrow. These results implicate signals could serve as potential targets for management.

Язык: Английский

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Lutetium177-Labeled DOTA-Ibandronate: A Novel Radiopharmaceutical for Targeted Treatment of Bone Metastases

Molecular Pharmaceutics, Год журнала: 2023, Номер 20(3), С. 1788 - 1795

Опубликована: Фев. 20, 2023

Bone metastases of malignant tumors significantly threaten the patient survival and quality life. We designed synthesized a novel bisphosphonate radiopharmaceutical [68Ga- or 177Lu-labeled DOTA-Ibandronate(68Ga/177Lu-DOTA-IBA)] for targeted diagnosis treatment bone metastases. This study explored basic biological characteristics 177Lu-DOTA-IBA, guiding clinical translation providing evidence future applications. The control variable method was used to optimize optimal labeling conditions. in vitro properties, distribution, toxicity 177Lu-DOTA-IBA were studied. Normal mice tumor-bearing imaged using micro SPECT/CT. With Ethics Committee approval, five volunteers recruited preliminary study. has radiochemical purity more than 98%, with good properties safety. Blood clearance is fast soft tissue uptake low. Tracers are excreted mainly through urinary system, targeting continuously concentrating bones. Three patients experienced significant pain relief within 3 days after (740-1110 MBq), lasting 2 months, no toxic side effects. easy prepare exhibits pharmacokinetic characteristics. Low-dose effective, well tolerated, associated adverse reactions. It promising metastases, controlling progress metastasis improving life advanced metastasis.

Язык: Английский

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Inflammatory Processes Affecting Bone Health and Repair

Current Osteoporosis Reports, Год журнала: 2023, Номер 21(6), С. 842 - 853

Опубликована: Сен. 28, 2023

Язык: Английский

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Bioactive elements manipulate bone regeneration.

PubMed, Год журнала: 2023, Номер 4(4), С. 248 - 269

Опубликована: Янв. 1, 2023

While bone tissue is known for its inherent regenerative abilities, various pathological conditions and trauma can disrupt meticulously regulated processes of formation resorption. Bone engineering aims to replicate the extracellular matrix as well sophisticated biochemical mechanisms crucial effective regeneration. Traditionally, field has relied on external agents like growth factors pharmaceuticals modulate these processes. Although efficacious in certain scenarios, this strategy compromised by limitations such safety issues transient nature compound release half-life. Conversely, bioactive elements zinc (Zn), magnesium (Mg) silicon (Si), have garnered increasing interest their therapeutic benefits, superior stability, reduced biotic risks. Moreover, are often incorporated into biomaterials that function multifaceted components, facilitating regeneration via on-demand. By elucidating mechanistic roles efficacy elements, review establish a robust clinically viable advanced

Язык: Английский

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Biomaterial design for regenerating aged bone: materiobiological advances and paradigmatic shifts

National Science Review, Год журнала: 2024, Номер 11(5)

Опубликована: Фев. 27, 2024

China's aging demographic poses a challenge for treating prevalent bone diseases impacting life quality. As regeneration capacity diminishes with age due to cellular dysfunction and inflammation, advanced biomaterials-based approaches offer hope aged regeneration. This review synthesizes materiobiology principles, focusing on biomaterials that target specific biological functions restore tissue integrity. It covers strategies stem cell manipulation, regulation of the inflammatory microenvironment, blood vessel regeneration, intervention in anabolism catabolism, nerve regulation. The also explores molecular mechanisms underlying proposes database-driven design process future biomaterial development. These insights may guide therapies other age-related conditions, contributing pursuit 'healthy aging'.

Язык: Английский

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Advancing bone biology: The mutual promotion of biology and pioneering technologies

The Innovation Life, Год журнала: 2024, Номер 2(3), С. 100078 - 100078

Опубликована: Янв. 1, 2024

<p>Bone is a mineralized tissue that provides fundamental support for body posture and biomechanical forces. Bones have also been meticulously used by humans as fine tools at least over 25,000 years, perpetually captivating our curiosity driving exploration into its mysteries. In this perspective, we revisit the milestones in history of bone biology since 17^th century, highlighted transformative impact pioneering technologies. From macroanatomical observations to microscopic cellular analyses molecular signaling pathway explorations, each milestone has heralded groundbreaking discoveries. These include elucidation Wollf’s Law, regulatory mechanisms calcium metabolism (via osteotropic parathyroid hormone analogs calcitonin), well revelation critical cell interactions pathways remodeling. foundational insights deepen understanding an enigmatic underexplored tissue, but yield significant clinical advancements. Bone stands poised explosive expansion knowledge usher era systems biology, propelled cutting-edge multi-omics approaches, including single RNA sequencing (scRNA-seq) spatial transcriptomics, artificial intelligence. Therefore, challenges future directions are discussed navigate complexities integrating emerging technologies foster interdisciplinary collaborations will propel research towards innovative breakthroughs holistic solutions.</p>

Язык: Английский

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Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Март 5, 2024

Abstract Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt the mechanical loading environment. However, it unclear whether signals of bone cells in response stress are processed interpreted brain. In this study, we found that hypothalamus brain regulates structure by perceiving prostaglandin E2 (PGE2) concentration loading. PGE2 levels proportion their weight bearing. When bearing changes tail-suspension mice, concentrations bones change line with changes. Deletion cyclooxygenase-2 (COX2) osteoblast lineage or knockout receptor 4 ( EP4) sensory nerve blunts formation Moreover, TrkA also significantly reduces load-induced formation. induces cAMP-response element binding protein (CREB) phosphorylation hypothalamic arcuate nucleus (ARC) inhibit sympathetic tyrosine hydroxylase (TH) expression paraventricular (PVN) for osteogenesis. Finally, show elevated associated ankle osteoarthritis (AOA) pain. Together, our data demonstrate loading, skeletal interoception occurs form processing PGE2-driven peripheral signaling maintain physiologic homeostasis, while chronically can be sensed as pain during AOA implication potential treatment.

Язык: Английский

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Skeletal interoception in osteoarthritis

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Апрель 1, 2024

Abstract The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of organism. Among its various forms, skeletal specifically regulates bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, synovium. bone undergoes continuous remodeling to adapt dynamic loads. Recent findings highlight that mediated aberrant mechanical loads contributes pathological resulting sclerosis OA. also potential mechanism for chronic synovial inflammation In this review, we offer general overview interoception, microenviroment remedeling. We discuss role abnormal OA, as well prospects challenges exploring novel OA therapies target interoception.

Язык: Английский

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