Holkar Ketki, Pethe Prasad, Kale Vaijayanti, Ingavle Ganesh
Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, India.
Clinical Research Facility, NIHR Biomedical Research Centre, Guy's & st Thomas' NHS Foundation Trust and King's College London, Guy's Hospital, London, UK.
J Biomed Mater Res A. 2025 Jun;113(6):e37947. doi: 10.1002/jbm.a.37947.
Efficient bone repair relies on both osteogenic and angiogenic signals, with growth factors playing a pivotal role. Despite decades of recognition of their therapeutic potential, the optimal dosages and delivery routes of growth factors still require extensive investigation. Previous research demonstrated the osteoinductive and angiogenic potential of growth factors. However, effective therapeutic outcomes depend on precise dosing and prolonged delivery. This study investigates the dual delivery of key growth factors, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), providing insights into their optimal dosages and delivery mechanisms. The combination of these growth factors may enhance scaffold-mediated bone regeneration in the early stages of healing. This study employed a dual delivery system using BMP-2 and VEGF, comparing two methods to determine the optimal dosage and delivery strategy. The combined effect indicates that sustained delivery is a more efficient method. Osteogenesis and angiogenesis were examined in an interpenetrating network (IPN) hydrogel composed of alginate and polyethylene diacrylate (PEGDA), which encapsulated preosteoblast MC3T3 cells. The findings of this study reveal significant increases in alkaline phosphatase (ALP) activity and calcium content, emphasizing the effectiveness of this approach. Biomaterial characterization, including swelling measurements, Fourier transform infrared (FTIR) spectroscopy, confirmed growth factor encapsulation, and a release assay validated the delivery process. Compared to direct delivery, sustained delivery increased ALP activity and calcium release by up to 1.12- and 1.85-fold, respectively. Molecular studies indicated that sustained delivery of both growth factors had a stronger osteoinductive and angiogenic effect than direct delivery. This research evaluates the effects of growth factor delivery in a 3D hydrogel-based microenvironment using hydrogels and compares delivery methods to identify a more effective strategy for bone healing.
高效的骨修复依赖于成骨信号和血管生成信号，生长因子在其中起着关键作用。尽管数十年来人们已认识到它们的治疗潜力，但生长因子的最佳剂量和递送途径仍需深入研究。先前的研究证明了生长因子的骨诱导和血管生成潜力。然而，有效的治疗效果取决于精确的剂量和持续的递送。本研究调查了关键生长因子骨形态发生蛋白-2（BMP-2）和血管内皮生长因子（VEGF）的双重递送，以深入了解它们的最佳剂量和递送机制。这些生长因子的组合可能会在愈合早期增强支架介导的骨再生。本研究采用了一种使用BMP-2和VEGF的双重递送系统，比较了两种方法以确定最佳剂量和递送策略。综合效果表明持续递送是一种更有效的方法。在由藻酸盐和聚乙二醇二丙烯酸酯（PEGDA）组成的互穿网络（IPN）水凝胶中检测了成骨作用和血管生成，该水凝胶包裹了前成骨细胞MC3T3细胞。本研究的结果显示碱性磷酸酶（ALP）活性和钙含量显著增加，强调了这种方法的有效性。生物材料表征，包括溶胀测量、傅里叶变换红外（FTIR）光谱，证实了生长因子的包裹，并且释放试验验证了递送过程。与直接递送相比，持续递送使ALP活性和钙释放分别增加了高达1.12倍和1.85倍。分子研究表明，两种生长因子的持续递送比直接递送具有更强的骨诱导和血管生成作用。本研究评估了在基于3D水凝胶的微环境中使用水凝胶递送生长因子的效果，并比较了递送方法以确定一种更有效的骨愈合策略。
