title: BMP7-Based Functionalized Self-Assembling Peptides for Nucleus Pulposus Tissue Engineering.
abstract: Nucleus pulposus (NP) tissue engineering has been demonstrated to be a feasible therapeutic strategy for intervertebral disc regeneration. In this study, we constructed a novel injectable biomaterial by conjugating three different short peptides of BMP7 to the C-terminus of the self-assembling peptide RADA16-I, and we then mixed each of these conjugates with RADA16-I at equal volumes to obtain the novel functionalized peptides RAD-SNV, RAD-KPS, and RAD-KAI. The bioactivities of these functionalized peptides for human degenerated NP cells (hdNPCs) were evaluated in vitro, and the most ideal scaffold was chosen for assessment of its in vivo degradation and the tissue reactions to it. All of the functionalized peptides self-assembled to form hydrogel scaffolds with a nanofibrous structure under physiological conditions. Compared with the RADA16-I and RAD-KAI scaffolds, the RAD-SNV and RAD-KPS scaffolds possessed better bioactivities for hdNPCs, which were characterized by their enhanced proliferation, migration, and ECM (collagen II, aggrecan, and sox-9) secretion. RAD-KPS was chosen over RAD-SNV as the most ideal scaffold material due to the cells' higher rate of expression of aggrecan both at the gene and protein level after 28 days of coculture. Moreover, in vivo analysis demonstrated that subcutaneously injected RAD-KPS degraded in vivo without invoking intense inflammation. Therefore, RAD-KPS is an ideal candidate scaffold for NP tissue engineering and holds great potential for NP regeneration.
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.|‡Department of Orthopaedic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: §The Third Affiliated Hospital of Southern Medical University, Guangzhou 510665, People's Republic of China.
authors.forename: Yaohong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Wang
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Tianyong
authors.initials: T
authors.lastname: Wen
authors.affiliation: ∥State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wang
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Deli
authors.initials: D
authors.lastname: Wang
authors.affiliation: †Department of Orthopaedic Surgery, Navy General Hospital, Beijing 100037, People's Republic of China.
authors.forename: Dike
authors.initials: D
authors.lastname: Ruan
mesh_terms: D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007403:Intervertebral Disc / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D049329:Nanostructures / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D055419:Bone Morphogenetic Protein 7; D010455:Peptides; C546681:RADA16-I; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: compatibility; degeneration; functional peptide; hydrogel; intervertebral disc; self-assembly