Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion  

作　　者：Xinggui Tian Corina Vater Deepak Bushan Raina Lisa Findeisen Lucas-Maximilian Matuszewski Magnus Tägil Lars Lidgren Anja Winkler Robert Gottwald Niels Modler Klaus-Dieter Schaser Alexander C.Disch Stefan Zwingenberger 

机构地区：[1]University Center of Orthopaedic,Trauma and Plastic Surgery,University Hospital Carl Gustav Carus at TUD Dresden University of Technology,01307,Dresden,Germany [2]Center for Translational Bone,Joint and Soft Tissue Research,University Hospital Carl Gustav Carus at TUD Dresden University of Technology,01307,Dresden,Germany [3]Lund University,Faculty of Medicine,Department of Clinical Sciences Lund,Orthopaedics,Lund,22185,Sweden [4]Institute of Lightweight Engineering and Polymer Technology at TUD Dresden University of Technology,01062,Dresden,Germany

出　　处：《Bioactive Materials》2024年第6期256-271,共16页生物活性材料（英文）

基　　金：L.L.thanks the Olav Thon Foundation(Grant Number:21-90)for financial support;D.B.R.thanks Maggie-Stephens Foundation(Grant Number:20202004);Sten K Johnson Foundation(Grant Number:2021-0592);The Crafoord Foundation(2021-0550)for research grants.

摘　　要：Recombinant human bone morphogenetic protein-2(rhBMP-2)has been FDA-approved for lumbar fusion,but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage.One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates,but it presents challenges with systemic side effects and low local bioavailability.The aim of this in vivo study was to analyze if posterolateral spinal fusion(PLF)could be improved by utilizing a calcium sulfate/hydroxyapatite(CaS/HA)carrier co-delivering rhBMP-2 and zoledronic acid(ZA).Six groups were allocated(CaS/HA,CaS/HA+BMP-2,CaS/HA+systemic ZA,CaS/HA+local ZA,CaS/HA+BMP-2+systemic ZA,and CaS/HA+BMP-2+local ZA).10-week-old male Wistar rats,were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds.At 3 and 6 weeks,the animals were euthanized for radiography,μCT,histological staining,or biomechanical testing to evaluate spinal fusion.The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn’t support PLF.However,the delivery of rhBMP-2 significantly promoted PLF.Combining systemic ZA with rhBMP-2 didn’t enhance spinal fusion.Notably,the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF,without inhibiting systemic bone turnover,and potentially reduced the dose of rhBMP-2.Together,the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

关 键 词：Calcium sulfate/hydroxyapatite Bone morphogenetic protein 2 BISPHOSPHONATE Spinal fusion Bone substitute 

分 类 号：R68[医药卫生—骨科学] R318[医药卫生—外科学]