Alendronate-Functionalized Polycaprolactone/Gelatin Electrospun Fibrous Membranes for Enhanced Osteogenesis and Antiosteoclastogenesis in Bone Regeneration
Document Type
Article
Subject Area(s)
Animals; Polyesters (chemistry); Bone Regeneration (drug effects); Osteogenesis (drug effects); Gelatin (chemistry); Mice; Alendronate (chemistry, pharmacology); Rats; RAW 264.7 Cells; Osteoclasts (drug effects, metabolism, cytology); Rats, Sprague-Dawley; Membranes, Artificial; Male
Abstract
For alveolar bone defects associated with osteoclast-active periodontitis, polycaprolactone (PCL)-based electrospun guided bone regeneration (GBR) membranes exhibit limited bone repair ability due to insufficient osteogenic promotion and inadequate osteoclast-targeted inhibition. To address these challenges, gelatin (GEL) was incorporated into the membranes to enhance their osteogenic capacity, while alendronate (ALN)─a bisphosphonate with both osteoclast inhibitory activity and osteogenic potential─was loaded at varying concentrations (1, 5, 10 wt %) to fabricate PG-1ALN, PG-5ALN, and PG-10ALN membranes. The membranes were characterized based on their physicochemical properties, and drug release studies confirmed that the PG-ALN group exhibited sustained ALN release over 28 days. In vitro, PG-1ALN enhanced isolated osteogenesis, but it showed limited efficacy in coculture systems, exhibiting a correlation with unchanged BMP-2 and OSM levels in RAW264.7-conditioned medium. In contrast, PG-5ALN exhibited osteoclast suppression in both isolated and coculture models, supported by the lowest RANKL/OPG ratio of 0.025 (four times lower than that of the PCL group). Micro-CT and histological (H&E, Masson staining) of rat cranial defects demonstrated PG-5ALN's superior bone regeneration; the bone volume fraction (BV) in the PG-5ALN group increased to 5.4 mm (control PCL group: 1.3 mm). The bone mineral density (BMD) in the PG-5ALN group rose to 0.30 g/cm (control PCL group: 0.036 g/cm), marked by dense OCN deposition and minimal TRAP-positive osteoclasts. Notably, PG-5ALN achieved optimal osteoimmunomodulation by balancing osteoblast activation and osteoclast inhibition, thereby advancing the design of dual-functional GBR membranes for osteoclast-active alveolar bone defects.
Digital Object Identifier (DOI)
Publication Info
Published in ACS Applied Materials & Interfaces, Volume 17, Issue 26, 2025, pages 37523-37538.
APA Citation
Xie, Z., Wu, Y., Lin, Y., Su, J., Yu, H., Lei, Y., Lin, Y., Wang, W., Wu, D., & Lai, Y. (2025). Alendronate-Functionalized Polycaprolactone/Gelatin Electrospun Fibrous Membranes for Enhanced Osteogenesis and Antiosteoclastogenesis in Bone Regeneration. ACS Applied Materials & Interfaces, 17(26), 37523–37538.https://doi.org/10.1021/acsami.5c05190
Rights
© 2025 American Chemical Society