title: Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface.
abstract: Biomaterial surface functionalized with bone morphogenetic protein-2 (BMP-2) is a promising approach to fabricating successful orthopedic implants/scaffolds. However, the bioactivity of BMP-2 on material surfaces is still far from satisfactory and the mechanism of related protein-surface interaction remains elusive. Based on the most widely used bone-implants/scaffolds material, hydroxyapatite (HAP), we developed a matrix of magnesium-substituted HAP (Mg-HAP, 2.2 at% substitution) to address these issues. Further, we investigated the adsorption dynamics, BMPRs-recruitment, and bioactivity of recombinant human BMP-2 (rhBMP-2) on the HAP and Mg-HAP surfaces. To elucidate the mechanism, molecular dynamic simulations were performed to calculate the preferred orientations, conformation changes, and cysteine-knot stabilities of adsorbed BMP-2 molecules. The results showed that rhBMP-2 on the Mg-HAP surface exhibited greater bioactivity, evidenced by more facilitated BMPRs-recognition and higher ALP activity than on the HAP surface. Moreover, molecular simulations indicated that BMP-2 favoured distinct side-on orientations on the HAP and Mg-HAP surfaces. Intriguingly, BMP-2 on the Mg-HAP surface largely preserved the active protein structure evidenced by more stable cysteine-knots than on the HAP surface. These findings explicitly clarify the mechanism of BMP-2-HAP/Mg-HAP interactions and highlight the promising application of Mg-HAP/BMP-2 matrixes in bone regeneration implants/scaffolds.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.|School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, 2 George St, Brisbane, QLD 4001, Australia.
authors.forename: Baolin
authors.initials: B
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.|Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, 2 George St, Brisbane, QLD 4001, Australia.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.|Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Sai
authors.initials: S
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.|Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, 2 George St, Brisbane, QLD 4001, Australia.
authors.forename: Yuantong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.|Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000327:Adsorption; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017886:Durapatite / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D017886:Durapatite; D008274:Magnesium