Platelet Responses to Urethane Dimethacrylate-Based Bone Cements Containing Monocalcium Phosphate/ε-Polylysine: Role of ε-Polylysine in In Vitro Wound Healing Induced by Platelet-Derived Growth Factor-BB

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Abstract
Platelets play a pivotal role in initiating bone fracture healing. However, the interaction between platelets and bone cements used for fracture repair remains relatively unexplored. This study investigated the platelet response to recently developed urethane dimethacrylate-based bone cements containing 8% (w/w) monocalcium phosphate monohydrate (MCPM) and/or 5% (w/w) epsilon-polylysine (PLS). All experimental bone cements achieved final monomer conversions of 75-78%, compared with the 86% conversion of the commercial PMMA bone cement Kyphon. The MCPM and PLS microparticles, varying in size, were dispersed within the glass-filler-incorporated polymer matrix. In contrast to Kyphon, all experimental cements exhibited significantly smoother and more hydrophilic surfaces. Bone cements incorporating PLS, with or without MCPM, effectively activated platelets by inducing cellular adhesion, aggregation, and extracellular-signal-regulated kinase (ERK) activation, comparable to Kyphon. Flow cytometry analysis demonstrated a statistically significant increase in CD62P-positive platelets following exposure to PLS-incorporated bone cements and exogenously administered PLS in a concentration-dependent manner, but not with Kyphon. A wound healing assay revealed a 2-fold enhancement in wound closure within 24 h and exceeding 85% at 48 h by bone cements containing PLS, with or without MCPM, and Kyphon. Notably, platelet-derived growth factor BB (PDGF-BB) secretion was significantly elevated, specifically after platelet exposure to PLS-incorporated bone cements, a phenomenon not observed with Kyphon. Interestingly, PDGF-BB neutralization attenuated wound closure induced by the PLS-incorporated bone cements. In conclusion, the urethane dimethacrylate-based bone cements containing PLS demonstrated a significant enhancement in platelet activation and PDGF-BB secretion, which, at least partly, enhanced in vitro wound closure. The results suggest that PDGF-BB plays a crucial role in the PLS-mediated enhancement of wound healing in these bone cements.
Funding Information
  • Thailand Science Research and Innovation (TUFF 65/2567)
  • Thammasat University
  • Newton Fund (13661)
  • Bualuang ASEAN Chair Professor (4/2022)

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