Nanotechnology-based Theranostic Technology for Bone Tissue Engineering

描述(由申请人提供) 摘要：美国国立卫生研究院院长新创新者奖申请书中详细介绍的研究的主要目标是设计下一代基于纳米技术的治疗(诊断+治疗)技术，该技术将促进非侵入性成像，同时能够有针对性地激活受阻的肌肉骨骼修复部位的愈合过程。由于创伤、疾病、衰老或绝经引起的骨丢失是一个日益严重的健康问题，新兴的骨组织工程领域正在寻求改善局灶性骨丢失的策略。建议的治疗声技术利用了创新的多功能纳米材料(单壁碳纳米管和金纳米粒子)的物理性质，以及由纳秒电磁脉冲诱导的声波现象，称为光声(PA)效应。基于PA的成像方法利用再生组织和含有纳米颗粒的支架或移植细胞之间的内在和外部光声对比来非侵入性地(在空间和时间上)对新骨形成和新生血管进行成像。光声治疗的独特和创新方法包括生物物理刺激，使祖细胞的分化偏向受控的成骨细胞，从而提高暴露区域骨形成的质量和数量。这些研究将提供新的见解，并为未来开发用于监测和治疗特定骨骼病理的综合成像和治疗技术奠定科学基础。一旦完全开发，这项技术可以广泛提供给公众，包括医疗服务不足的人群，因为作为一种成像方式，它将是非电离的、用户友好的，并且比用于监测骨再生的其他3D成像方式成本更低；作为一种治疗方式，它将适合在治疗期间能够或无法站立的对象(如虚弱的老年人、脊髓损伤、只能坐轮椅或卧床、体验太空旅行)。 公共卫生相关性：由于创伤、疾病、衰老或更年期造成的骨丢失是一个日益严重的健康问题。这项提议将提供新的见解，并为未来开发一种治疗(综合治疗和诊断)技术奠定科学基础，该技术在特定骨骼病理的单一背景下结合非侵入性成像和治疗；最终，随着这一原则的确定，有可能开发出更广泛的需要有针对性的检测和治疗的损伤或疾病。一旦完全开发，这项技术可以广泛应用于公众，包括医疗服务不足的人群，因为作为一种成像方式，它将是非电离、用户友好型，并且成本低于其他用于监测骨再生的3D成像方式；作为一种治疗方式，它将适合在骨整合、骨折愈合、骨质疏松症和类似疾病的治疗过程中能够或无法站立的对象(如虚弱的老年人、脊髓损伤、只能坐轮椅或卧床休息、体验太空旅行)。

DESCRIPTION (Provided by the applicant) Abstract: The principal objective of the studies detailed in this application for the NIH Director's New Innovator Award is to engineer the next generation of nanotechnology-based theranostic (diagnostic + therapeutic) technology that will facilitate non-invasive imaging, and at the same time enable targeted activation of the healing process at sites of hampered musculoskeletal repair. Bone loss, due to trauma, disease, aging, or menopause is an increasingly serious health problem, and the emerging field of bone tissue engineering seeks to develop strategies to ameliorate focal bone loss. The proposed theranostic technology harnesses the physical properties of innovative multifunctional nanomaterials (single-walled carbon nanotubes and gold nanoparticles), and an acoustic wave phenomenon induced by nanosecond electromagnetic pulses known as the photoacoustic (PA) effect. The PA-based imaging approach exploits the combined intrinsic and extrinsic photoacoustic contrast between regenerating tissues and scaffolds or transplanted cells containing nanoparticles to non-invasively image (spatially and temporally) de novo bone formation and neo- vascularization. The unique and innovative approach for photoacoustic treatment involves a biophysical stimulus to bias the differentiation of progenitor cells towards controlled osteoblastogenesis thereby enhancing the quality and quantity of bone formation in the exposed region. The investigations will provide new insights, and lay the scientific foundation for future development of an integrated imaging and therapeutic technology to monitor and treat specific skeletal pathologies. Upon complete development, this technology could be made widely available to the general public, including medically under-served populations since, as an imaging modality, it will be non-ionizing, user-friendly and cost less than other 3D imaging modalities used to monitor bone regeneration; as a therapeutic modality, it would be suitable for subjects able or unable to stand (e.g., frail elderly, spinal cord injury, confined to wheelchairs or bed-rest, experience space travel) during treatment. Public Health Relevance: Bone loss, due to trauma, disease, aging, or menopause is an increasingly serious health problem. This proposal will provide new insights, and lays the scientific foundation for future development of a theranostic (integrated therapeutic and diagnostic) technology for combined non-invasive imaging and treatment in a single setting of specific skeletal pathologies; ultimately, with this proof of principal defined, there is the possibility of development for a wider range of injuries or diseases which require targeted detection, and treatment. Upon complete development, this technology could be made widely available to the general public, including medically under-served populations since, as an imaging modality, it will be non-ionizing, userfriendly and costs less than other 3D imaging modalities used to monitor bone regeneration; as a therapeutic modality, it would be suitable for subjects able or unable to stand (e.g., frail elderly, spinal cord injury, confined to wheelchairs or bed-rest, experience space travel) during treatment for osteo-integration, fracture healing, osteoporosis and similar diseases.