Establishment Of UHMWPE Wear Debris Induced Aseptic Loosening Animal Model And The Anti-peri-implant Osteolysis Effect Of Bisphosphonate Composed HA Coating

The number of total joint replacement increases steadily as the population becomes older. Then a big problem that more and more patients need at least once revision surgeries appears. And the primary cause for these revisions, besides infection, is aseptic loosening. Wear debris, especially UHMWPE particles, induced peri-implant osteolysis is reported to be a leading cause of aseptic loosening.Many researches have proved that the durability of uncemented implants is highly dependent on biological fixation. Early prosthetic migration is associated with high risk of aseptic loosening. Hence, the initial fixation of the implant is crucial for the success of the implant. The rapid and sustained bone ingrowth can provide stable fixation of implants and prevent migration. The more extensive the peri-implant bone formation, the more protected the bone–implant interface is against wear debris induced peri-implant osteolysis. The HA coating has been shown that it improves the implant stability, interface strength and fatigue resistance, bone mineralization, and bone ingrowth rate. Also, the use of bisphosphonates as adjuvant could also be a good way to enhance the early implant fixation.Several studies have been recently performed to combine implant and bisphosphonate, the results showed that this approach stimulated new bone formation around the implant and increased mechanical stability.Then, the interests are:1.There isn't a proper artificial joint aseptic loosening animal model which works according with pathology mechanism and costs less.2.Whether alendronate composed with HA-coating can inhibit UHMWPE particles induced peri-implant osteolysis?3.Whether alendronate can affect the osteoblast activity?4.Whether local delivered alendronate has systematic curative effect?5.Whether HA-coating implant composed with alendronate can work as a proper drug delivery carrier.Therefore, we established a UHMWPE particles induced New England rabbit artificial joint aseptic loosening animal model. And based on this new animal model, we have pathology, imaging, bone histomorphometry and biomechamics observations to further invest. The details are as follows:1.X-rayAnteroposterior radiographs were made immediately to measure the cortical bone thickness of bilateral tibial isthmus.2.Histological testThe synovium of the knee was retrieved and stained with HE. HE-stained sections were analyzed by light microscopy and polarized light microscopy. 3.Biomechanical testWe used pull-out test to describe load-displacement curve, then we calculate ultimate shear strength, apparent shear stiffness and total energy absorption.4.Bone histomorphometryWe used tetracycline double labeling and toluidine blue staining to reckon dynamic and static parameters. According to ASBMR nomenclature, we measured BV/TV, Tb.Th, Tb.N, OS/BS, O.Th, BFR/BS, MAR and E-MAR.The parameters of bone-to-implant contact and bone volume fraction were measured with modified ponceau trichrome stain section.Also, the parameters of calcium deposit islands (average area, number and area percentage) were measured with VON KOSSA stain section.5.SEMThe specimens were observed in scanning electron microscope with normal mode and backscattered mode allowing to observe the superficial shape and to distinguish the mineralized bone from soft tissue. The bone volume fraction was measured at a distance of 200μm, 200-500μm and 500-800μm respectively from the surface of the implant in the treatment side and at a distance from the endosteum of 800μm in bilateral sides.6.Ash WeightAsh weight measurements were performed. The right ulna bones were weighed to determine wet weight (Ww), and then burned separately to determine dry ash weight (Wa) and weight fraction (Wa/Ww).7.DEXADEXA measurement was performed to measure the bone density of the second lumber.8.Alendronate release time Then the elution curve of the percent release of alendronate was painted to evaluate the drug release characteristics from non-porous HA-coating implant.The results showed that local alendronate delivery increased cortical bone thickness, trabecula parameters, osteoblast activity, bone mineralization, and bone density of both treatment side and contralateral side; and increased cortical bone thickness, biomechanical implant fixation, bone-to-implant contact, peri-implant bone volume fraction, bone mineralization, and peri-implant bone density of treatment side significantly.Conclusion:1.The New England rabbit artificial joint aseptic loosening animal model we established is suitable for related researches.2.Alendronate composed with HA-coating can inhibit UHMWPE particles induced peri-implant osteolysis in vivo, which even works better than with the absence of UHMWPE particles.3.Alendronate can activate the osteoblast in vivo.4.Local delivered alendronate has systematic curative effect.5.HA-coating implant composed with alendronate can work as a proper drug delivery carrier.