4.7 Article

Zoledronic Acid Implant Coating Results in Local Medullary Bone Growth

Journal

MOLECULAR PHARMACEUTICS
Volume 19, Issue 12, Pages 4654-4664

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.2c00644

Keywords

zoledronat; PLGA; titanium implant; bone regeneration; osteoarthritis

Funding

  1. Alfred P. Sloan Foundation
  2. University of Iowa Graduate College
  3. American Association for University Women
  4. NIH [1R21DE031042-01A1, P30 CA086862]
  5. Lyle and Sharon Bighley Chair of Pharmaceutical Sciences
  6. Keith Guillory Pharmaceutics Graduate Research Fellowship
  7. University of Iowa College of Pharmacy

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Osteoarthritis patients may require revision surgery after joint replacement due to prosthetic loosening. Coating with zoledronic acid (ZA) has been shown to enhance implant osseointegration, as evidenced by in vitro and in vivo experiments.
Osteoarthritis (OA) can necessitate surgical interventions to restore the function of the joint in severe cases. Joint replacement surgery is one of the procedures implemented to replace the damaged joint with prosthetic implants in severe cases of OA. However, after successful implantation, a fraction of OA patients still require revision surgery due to aseptic prosthetic loosening. Insufficient osseointegration is one of the factors that contribute to such loosening of the bone implant, which is commonly made from titanium-based materials. Zoledronic acid (ZA), a potent bisphosphonate agent, has been previously shown to enhance osseointegration of titanium implants. Herein, we fabricated ZA/Ca composites using a reverse microemulsion method and coated them with 1,2-dioleoyl-sn-glycero-3-phosphate monosodium salt (DOPA) to form ZA/Ca/DOPA composites. Titanium alloy screws were subsequently dip-coated with a suspension of the ZA/Ca/DOPA composites and poly(lactic-co-glycolic) acid (PLGA) in chloroform to yield Za/PLGA-coated screws. The coated screws exhibited a biphasic in vitro release profile with an initial burst release within 48 h, followed by a sustained release over 1 month. To assess their performance in vivo, the Za/PLGA screws were then implanted into the tibiae of Sprague-Dawley rats. After 8 weeks, microCT imaging showed new bone growth along the medullary cavity around the implant site, supporting the local release of ZA to enhance bone growth around the implant. Histological staining further confirmed the presence of new mineralized medullary bone growth resembling the cortical bone. Such local medullary growth represents an opportunity for future studies with alternative coating methods to fine-tune the local release of ZA from the coating and enhance complete osseointegration of the implant.

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