Modelling skeletal pain harnessing tissue engineering.
Modelling skeletal pain harnessing tissue engineering.
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DOI：
10.1007/s44164-022-00028-7
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发表时间：
2022
期刊：
影响因子：
--
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--
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骨痛通常在骨骼损伤后立即发生，伴随机械扭曲或伤害性纤维破裂。疼痛机制也与愈合过程受损的慢性疼痛状况有关。冲击骨折骨区域的任何负荷都会刺激伤害性反应，需要快速临床干预以缓解与骨损伤相关的疼痛，并适当缓解与骨量、肌肉和活动性损失相关的任何过程，并防止死亡。下面的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，重点是开发创新性治疗干预措施的新方法。特别是，审查强调组织工程的方法，提供了相当大的承诺，在骨和神经组织的功能仿生制造的应用。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，这些平台能够取代体内模型并测试旨在解决骨相关疼痛的新型药物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，与人类生理反应相关的数据很少。这篇综述探讨了疼痛药物开发研究中的明显差距，并提出了利用组织工程技术来概括受损骨组织复杂的病理生理学环境的方法的一步变化，从而能够评估相关的疼痛模拟机制，具有显著的治疗潜力，可改善患者的生活质量。新药测试平台开发的基本原理。通过中枢神经系统检测到的疼痛和骨折后的疼痛不能使用标准化方法治疗或完全缓解。疼痛机制和特异性/镇痛药物的疗效仍然知之甚少。体内和离体模型尚不能概括与骨骼损伤相关的各种疼痛事件。体外模型目前受到其不能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的任何破坏的限制。需要稳健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
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. 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
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