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Overcoming barriers confronting application of protein therapeutics in bone fracture healing
1Advanced Drug Delivery Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH, 44272, USA.
Abstract:
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.
Insights
Developing effective drug delivery systems is crucial for advancing osteogenic protein therapeutics to accelerate bone fracture healing. This review evaluates platforms to overcome delivery challenges and improve safety and efficacy for clinical translation.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Orthopedic Surgery
Background:
- Bone fractures are a significant cause of morbidity and mortality, particularly in aging populations.
- Osteogenic protein therapeutics, like bone morphogenic protein-2 (BMP-2), show promise for fracture healing but face delivery challenges.
- Effective drug delivery systems are essential to enhance the safety and efficacy of protein therapeutics for bone regeneration.
Purpose of the Study:
- To review various drug delivery platforms and biomaterials for osteogenic protein delivery in bone regeneration.
- To assess clinical considerations, administration routes (implantable vs. injectable), and evaluation methodologies for these platforms.
- To provide insights for future research directions towards clinically translatable osteogenic protein therapeutics.
Main Methods:
- Literature review of drug delivery platforms and biomaterials for bone regeneration.
- Analysis of administration routes, including implantable and injectable strategies.
- Evaluation of safety and efficacy assessment models and methodologies for protein-loaded systems.
Main Results:
- Several drug delivery platforms and biomaterials show potential for overcoming challenges in therapeutic protein delivery for bone regeneration.
- Implantable and injectable routes offer different clinical considerations for administration.
- Standardized models and methodologies are crucial for evaluating the safety and efficacy of these systems.
Conclusions:
- Drug delivery systems are imperative for enhancing the safety and efficacy of osteogenic protein therapeutics.
- Further research and development of clinically translatable platforms are needed to establish osteogenic proteins as first-line treatments for fracture healing.
- This review provides a framework for evaluating and advancing therapeutic protein delivery systems in bone regeneration.
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