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Modelling skeletal pain harnessing tissue engineering. 利用组织工程建模骨骼疼痛。
Pub Date : 2022-01-01 Epub Date: 2022-08-04 DOI: 10.1007/s44164-022-00028-7
Lucia Iafrate, Maria Cristina Benedetti, Samantha Donsante, Alessandro Rosa, Alessandro Corsi, Richard O C Oreffo, Mara Riminucci, Giancarlo Ruocco, Chiara Scognamiglio, Gianluca Cidonio

Bone pain typically occurs immediately following skeletal damage with mechanical distortion or rupture of nociceptive fibres. The pain mechanism is also associated with chronic pain conditions where the healing process is impaired. Any load impacting on the area of the fractured bone will stimulate the nociceptive response, necessitating rapid clinical intervention to relieve pain associated with the bone damage and appropriate mitigation of any processes involved with the loss of bone mass, muscle, and mobility and to prevent death. The following review has examined the mechanisms of pain associated with trauma or cancer-related skeletal damage focusing on new approaches for the development of innovative therapeutic interventions. In particular, the review highlights tissue engineering approaches that offer considerable promise in the application of functional biomimetic fabrication of bone and nerve tissues. The strategic combination of bone and nerve tissue engineered models provides significant potential to develop a new class of in vitro platforms, capable of replacing in vivo models and testing the safety and efficacy of novel drug treatments aimed at the resolution of bone-associated pain. To date, the field of bone pain research has centred on animal models, with a paucity of data correlating to the human physiological response. This review explores the evident gap in pain drug development research and suggests a step change in approach to harness tissue engineering technologies to recapitulate the complex pathophysiological environment of the damaged bone tissue enabling evaluation of the associated pain-mimicking mechanism with significant therapeutic potential therein for improved patient quality of life.

Graphical abstract: Rationale underlying novel drug testing platform development. Pain detected by the central nervous system and following bone fracture cannot be treated or exclusively alleviated using standardised methods. The pain mechanism and specificity/efficacy of pain reduction drugs remain poorly understood. In vivo and ex vivo models are not yet able to recapitulate the various pain events associated with skeletal damage. In vitro models are currently limited by their inability to fully mimic the complex physiological mechanisms at play between nervous and skeletal tissue and any disruption in pathological states. Robust innovative tissue engineering models are needed to better understand pain events and to investigate therapeutic regimes.

骨痛通常发生在骨骼损伤后,伴随着伤害性纤维的机械变形或断裂。疼痛机制也与慢性疼痛有关,其中愈合过程受到损害。任何影响骨折区域的负荷都会刺激伤害反应,需要快速的临床干预来缓解与骨损伤相关的疼痛,并适当缓解与骨量、肌肉和活动能力丧失有关的任何过程,以防止死亡。以下综述研究了与创伤或癌症相关的骨骼损伤相关的疼痛机制,重点是开发创新治疗干预措施的新方法。特别是,该综述强调了组织工程方法,这些方法在骨和神经组织的功能仿生制造应用中具有相当大的前景。骨和神经组织工程模型的战略组合为开发一类新的体外平台提供了巨大的潜力,该平台能够取代体内模型,并测试旨在解决骨相关疼痛的新药治疗的安全性和有效性。迄今为止,骨痛研究领域主要集中在动物模型上,缺乏与人类生理反应相关的数据。这篇综述探讨了疼痛药物开发研究中的明显差距,并建议逐步改变利用组织工程技术来概括受损骨组织复杂的病理生理环境的方法,从而能够评估相关的疼痛模拟机制,该机制具有显著的治疗潜力,可提高患者的生活质量。图形摘要:新型药物测试平台开发的基本原理。中枢神经系统检测到的疼痛和骨折后的疼痛无法使用标准化方法进行治疗或完全缓解。镇痛药物的疼痛机制和特异性/疗效仍知之甚少。体内和离体模型还不能概括与骨骼损伤相关的各种疼痛事件。目前,体外模型由于无法完全模拟神经和骨骼组织之间的复杂生理机制以及病理状态下的任何破坏而受到限制。需要强有力的创新组织工程模型来更好地理解疼痛事件并研究治疗方案。
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引用次数: 3
Welcome to In vitro models 欢迎来到体外模型
Pub Date : 2021-10-28 DOI: 10.1007/s44164-021-00002-9
J. M. Oliveira, K. Popat
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引用次数: 0
Cortical Spheroid Model for Studying the Effects of Ischemic Brain Injury 研究缺血性脑损伤影响的皮质球体模型
Pub Date : 2021-10-16 DOI: 10.1007/s44164-023-00046-z
Rachel M. McLaughlin, A. Laguna, Ilayda Top, Christien Hernandez, L. Livi, Liana Kramer, Samantha G. Zambuto, D. Hoffman-Kim
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引用次数: 0
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In vitro models
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