Advanced Drug Delivery Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH, 44272, USA.
Drug Deliv Transl Res. 2021 Jun;11(3):842-865. doi: 10.1007/s13346-020-00829-x.
Bone fracture is a major contributor to debilitation and death among patients with bone diseases. Thus, osteogenic protein therapeutics and their delivery to bone have been extensively researched as strategies to accelerate fracture healing. To prevent morbidity and mortality of fractures, which occur frequently in the aging population, there is a critical need for development of first-line therapeutics. Bone morphogenic protein-2 (BMP-2) has been at the forefront of bone regeneration research for its potent osteoinduction, despite safety concerns and biophysiological obstacles of delivery to bone. However, continued pursuit of osteoinductive proteins as a therapeutic option is largely aided by drug delivery systems, playing an imperative role in enhancing safety and efficacy. In this work, we highlighted several types of drug delivery platforms and their biomaterials, to evaluate the suitability in overcoming challenges of therapeutic protein delivery for bone regeneration. To showcase the clinical considerations for each type of platform, we have assessed the most common route of administration strategies for bone regeneration, classifying the platforms as implantable or injectable. Additionally, we have analyzed the commonly utilized models and methodology for safety and efficacy evaluation of these osteogenic protein-loaded systems, to present clinical opinions for future directions of research in this field. It is hoped that this review will promote research and development of clinically translatable osteogenic protein therapeutics, while targeting first-line treatment status for achieving desired outcomes of fracture healing. Graphical abstract.
骨骨折是导致骨骼疾病患者衰弱和死亡的主要原因。因此，人们广泛研究了成骨蛋白治疗及其向骨骼的输送，以加速骨折愈合。为了预防经常发生在老年人群中的骨折的发病率和死亡率，迫切需要开发一线治疗方法。骨形态发生蛋白-2（BMP-2）因其强大的成骨诱导作用而成为骨再生研究的前沿，但由于其安全性问题和向骨骼输送的生物物理障碍，其应用受到限制。然而，由于药物输送系统的帮助，继续将诱导成骨蛋白作为一种治疗选择，在提高安全性和疗效方面发挥着至关重要的作用。在这项工作中，我们强调了几种药物输送平台及其生物材料，以评估它们在克服治疗性蛋白输送以促进骨再生方面的挑战的适用性。为了展示每种平台的临床考虑因素，我们评估了用于骨再生的最常见的给药途径策略，将平台分类为可植入或可注射。此外，我们还分析了这些成骨蛋白负载系统的安全性和有效性评估中常用的模型和方法，为该领域的未来研究方向提供临床意见。希望本综述能促进具有临床转化潜力的成骨蛋白治疗的研究与开发，同时针对一线治疗地位，以实现骨折愈合的预期结果。
