Addition of heparin binding sites strongly increases the bone forming capabilities of BMP9 in vivo

作     者：Claudia Siverino Shorouk Fahmy-Garcia Viktoria Niklaus Nicole Kops Laura Dolcini Massimiliano Maraglino Misciagna Yanto Ridwan Eric Farrell Gerjo JVMvan Osch Joachim Nickel 

作者机构：Department of Tissue Engineering and Regenerative MedicineUniversity Hospital WuerzburgWuerzburgGermany Department of Orthopaedics and Sports MedicineErasmus MCUniversity Medical CenterRotterdamthe Netherlands Department of Internal MedicineErasmus MCUniversity Medical CenterRotterdamthe Netherlands Department of Oral and Maxillofacial SurgeryErasmus MCUniversity Medical CenterRotterdamthe Netherlands Fin-Ceramica Faenza SpAVia Granarolo 177/348018FaenzaItaly AMIE Core FacilityErasmus University Medical CenterRotterdamthe Netherlands Department of OtorhinolaryngologyHead and Neck SurgeryErasmus MCUniversity Medical CenterRotterdamthe Netherlands Department of Biomechanical EngineeringFaculty of MechanicalMaritime and Materials EngineeringDelft University of TechnologyDelftthe Netherlands Fraunhofer ISCTranslational Center RTWuerzburgGermany 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第29卷第11期

页      面：241-250页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 080502[工学-材料学] 0836[工学-生物工程] 

基　　金：European Union Seventh Framework Programme FP7-PEOPLE-2013-ITN Netherlands Organisation of Scientific Research – Applied and Engineering Science Julius-Maximilians-Universität Würzburg, JMU EuroNanoMed III, ENM III, (ENMIII077-2) Seventh Framework Programme, FP7, (607051) 

主　　题：Bone morphogenetic protein 9(BMP9) Heparin binding sites Bone regeneration Subcutaneous animal model 

摘      要：Bone Morphogenetic proteins(BMPs)like BMP2 and BMP7 have shown great potential in the treatment of severe bone *** recent in vitro studies,BMP9 revealed the highest osteogenic potential compared to other BMPs,possibly due to its unique signaling pathways that differs from other osteogenic ***,in vivo the bone forming capacity of BMP9-adsorbed scaffolds is not superior to BMP2 or *** silico analysis of the BMP9 protein sequence revealed that BMP9,in contrast to other osteogenic BMPs such as BMP2,completely lacks so-called heparin binding motifs that enable extracellular matrix(ECM)interactions which in general might be essential for the BMPs’osteogenic ***,we genetically engineered a new BMP9 variant by adding BMP2-derived heparin binding motifs to the N-terminal segment of BMP9′s mature *** resulting protein(BMP9 HB)showed higher heparin binding affinity than BMP2,similar osteogenic activity in vitro and comparable binding affinities to BMPR-II and ALK1 compared to ***,remarkable differences were observed when BMP9 HB was adsorbed to collagen scaffolds and implanted subcutaneously in the dorsum of rats,showing a consistent and significant increase in bone volume and density compared to BMP2 and *** at 10-fold lower BMP9 HB doses bone tissue formation was *** innovative approach of significantly enhancing the osteogenic properties of BMP9 simply by addition of ECM binding motifs,could constitute a valuable replacement to the commonly used *** possibility to use lower protein doses demonstrates BMP9 HB’s high translational potential.