Key Takeaways & Executive Findings
- •• Hydrogel-based delivery platforms enhance the therapeutic efficacy of bioactive molecules for bone regeneration by prolonging retention, extending half-lives, and reducing side effects. • Integration of nano-/microscale carriers (e.g., nanoparticles, nanosheets, microspheres) with hydrogels enables controlled and stimuli-responsive release of bioactive molecules. • The review covers applications in cranial and femoral defect repair, periodontal bone regeneration, and bone regeneration under diseased conditions, highlighting versatility. • Challenges and future directions include clinical translation, scalability, and development of multi-functional delivery systems for improved bone repair outcomes.
Abstract
Bioactive molecules have shown great promise for effectively regulating various bone formation processes, rendering them attractive therapeutics for bone regeneration. However, the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo. Hydrogels have emerged as ideal carriers to address these challenges, offering the potential to prolong retention times at lesion sites, extend half-lives in vivo and mitigate side effects, avoid burst release, and promote adsorption under physiological conditions. This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration, encompassing applications in cranial defect repair, femoral defect repair, periodontal bone regeneration, and bone regeneration with underlying diseases. Additionally, this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery, carrier-assisted delivery, and sequential delivery. Finally, this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
1. Introduction
Bone tissue is a vital component of the human body, comprising one of the fundamental organ systems that provides essential support for movement, and playing a pivotal role in facilitating physical activity. Additionally, bone tissue can safeguard the vital organs and regulate the cellular metabolism. Consequently, maintaining the health of bone tissue is imperative for fostering social participation and is a critical determinant of an individual’s quality of life [1]. However, approximately 50% of adults, and particularly the aged population, experience bone injuries or defects [2]. These issues are usually induced by trauma, diseases, and other factors [3, 4]. The gold standard treatments for bone repair predominantly involve autografts, allografts, and internal fixation [5, 6]. Although these approaches have gained widespread acceptance, certain drawbacks are evident, including the limited availability of donor tissues, risk of infection, potential immunogenicity, and other associated concerns [7–9].
Bone tissue exhibits inherently dynamic and vascularized characteristics, thereby rendering it highly regenerative. Indeed, controlling the osteoblast function has been demonstrated to significantly enhance new bone formation and increase bone mass [10]. Therefore, various bioactive molecules, including drugs [11, 12], growth factors (GFs) [13, 14], stem cells [15], extracellular vesicles (EVs) [16, 17], and bioactive ions [18, 19], have been applied to bone regeneration in various pathological conditions. These molecules act directly on the injured bone tissue and demonstrate satisfactory therapeutic efficacies. However, several challenges remain unaddressed. For instance, a low in vivo stability and poor retention capability at the lesion site may require the high-dose administration of bioactive molecules, causing an increased toxicity toward normal tissues, and the potential for developing multidrug resistance. Generally, bone regeneration is a time-consuming process, rendering it crucial to construct a suitable platform for delivering bioactive molecules to injured bone sites and achieving a sustained release. In recent years, several nanomaterial-based carriers, including nanoparticles (NPs) [20, 21], graphene oxide (GO) /black phosphorus (BP) nanosheets (NSs) [22, 23], metal–organic frameworks (MOFs) [24, 25], and nanomicelles [26, 27], have been proposed as delivery systems for bioactive molecules. However, the direct administration of these carriers is essential for further discussion because of their elusive [truncated]
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Xiao Wang, Jia Zeng, Donglin Gan, Kun Ling, Mingfang He, Jianshu Li, Yongping Lu (2024). Recent Strategies and Advances in Hydrogel-Based Delivery Platforms for Bone Regeneration. Nano-Micro Letters. https://doi.org/10.1007/s40820-024-01557-4
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Frequently Asked Questions
What are the main advantages of using hydrogels for bone regeneration?
Hydrogels offer several advantages for bone regeneration, including prolonged retention at the lesion site, extended half-lives of bioactive molecules in vivo, reduced side effects, avoidance of burst release, and enhanced adsorption under physiological conditions.
How do nano-/microscale carriers improve hydrogel-based delivery systems?
Nano-/microscale carriers such as nanoparticles, nanosheets, and microspheres can be integrated into hydrogels to provide controlled and sustained release of bioactive molecules, enabling stimuli-responsive delivery (e.g., near-infrared light, temperature, ultrasonication) and sequential delivery for enhanced bone repair.
What types of bone defects can be treated with hydrogel-based delivery platforms?
These platforms have been applied to various bone defects, including cranial defect repair, femoral defect repair, periodontal bone regeneration, and bone regeneration in the presence of underlying diseases such as osteoporosis or diabetes.
What are the current challenges in clinical translation of hydrogel-based delivery systems?
Challenges include ensuring biocompatibility and safety, achieving scalable manufacturing, maintaining long-term stability, and developing multi-functional systems that can precisely control release kinetics and integrate with host tissue for effective regeneration.
What future directions are suggested for hydrogel-based bone regeneration?
Future directions include the development of smart hydrogels with multiple stimuli-responsive capabilities, incorporation of advanced nano-/microscale carriers for spatiotemporal control, and personalized medicine approaches to address patient-specific needs.
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