Abstract
BackgroundIn fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site.MethodsZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10.ResultsHistological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (p < 5%). In the ZOL group bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects.ConclusionThis study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature.
Highlights
In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance
Orthopedic titanium implants such as bone screws have been widely used for some decades in the treatment of acute and degenerative bone and joint defects affecting millions of people worldwide
AddBIO biocoated the screws with a fibrinogen multilayer and subsequently loaded them with 150 ng/cm2 of Zoledronic acid (ZOL) in a process modified from Tengvall [25]
Summary
Adequate fixation of implants is crucial to long-term clinical performance. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site Orthopedic titanium implants such as bone screws have been widely used for some decades in the treatment of acute and degenerative bone and joint defects affecting millions of people worldwide. Long-term bisphosphonate treatment is thought to adversely impact on bone metabolism, causing an enhanced risk of atypical low-energy fractures [23]. To prevent such complications whilst at the same time positively affecting peri-implant bone remodelling, innovative methods allowing a local release of bisphosphonates have been successfully developed [24]. Local release of Pamidronate and Ibandronate from fibrinogen coated implants has been successfully studied in rats [25,26,27,28]
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