Rationally designed bioactive milk-derived protein scaffolds enhanced new bone formation

作     者：Min Suk Lee Jin Jeon Sihyeon Park Juhan Lim Hee Seok Yang 

作者机构：Department of Nanobiomedical Science&BK21 FOUR NBM Global Research Center for Regenerative MedicineDankook UniversityCheonan31116Republic of Korea Medical Laser Research CenterCollege of MedicineDankook UniversityCheonan31116Republic of Korea Center for Bio-Medical Engineering Core-FacilityDankook UniversityCheonan31116Republic of Korea 

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

年 卷 期：2023年第20卷第2期

页      面：368-380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）] 

基　　金：supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2020R1A6A3A01098495,2020R1A6A1A03043283) by the Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Korean government(MSIT)(2018M3A9E2023259) supported by Basic Science Research Capacity Enhancement Project through Korea Basic Science Institute(National research Facilities and Equipment Center)grant funded by the Ministry of Education(2019R1A6C1010033). 

主　　题：Casein Bioactive peptides Bone regeneration Protein based scaffold Physical crosslinking 

摘      要：Recently,a number of studies reported that casein was composed of various multifunctional bioactive peptides such as casein phosphopeptide andβ-casochemotide-1 that bind calcium ions and induce macrophage chemotaxis,which is crucial for bone homeostasis and bone fracture repair by cytokines secreted in the process.We hypothesized that the effects of the multifunctional biopeptides in casein would contribute to improving bone regeneration.Thus,we designed a tissue engineering platform that consisted of casein and polyvinyl alcohol,which was a physical-crosslinked scaffold(milk-derived protein;MDP),via simple freeze-thaw cycles and performed surface modification using 3,4-dihydroxy-L-phenylalanine(DOPA),a mussel adhesive protein,for immobilizing adhesive proteins and cytokines for recruiting cells in vivo(MDP-DOPA).Both the MDP and MDP-DOPA groups proved indirectly contribution of macrophages migration as RAW 264.7 cells were highly migrated toward materials by contained bioactive peptides.We implanted MDP and MDP-DOPA in a mouse calvarial defect orthotopic model and evaluated whether MDP-DOPA showed much faster mineral deposition and higher bone density than that of the no-treatment and MDP groups.The MDP-DOPA group showed the accumulation of host M2 macrophages and mesenchymal stem cells(MSCs)around the scaffold,whereas MDP presented mostly M1 macrophages in the early stage.