title: Co‑delivery and controlled release of stromal cell‑derived factor‑1α chemically conjugated on collagen scaffolds enhances bone morphogenetic protein‑2‑driven osteogenesis in rats.
abstract: There has been considerable focus in investigations on the delivery systems and clinical applications of bone morphogenetic protein‑2 (BMP‑2) for novel bone formation. However, current delivery systems require high levels of BMP‑2 to exert a biological function. There are several concerns in using of high levels of BMP‑2, including safety and the high cost of treatment. Therefore, the development of strategies to decrease the levels of BMP‑2 required in these delivery systems is required. In our previous studies, a controlled‑release system was developed, which used Traut's reagent and the cross‑linker, 4‑(N‑maleimi‑domethyl) cyclohexane‑1‑carboxylic acid 3‑sulfo‑N‑hydroxysuccinimide ester sodium salt (Sulfo‑SMCC), to chemically conjugate BMP‑2 directly on collagen discs. In the current study, retention efficiency and release kinetics of stromal cell‑derived factor‑1α (SDF‑1α) cross‑linked on collagen scaffolds were detected. In addition, the osteogenic activity of SDF‑1α and suboptimal doses of BMP‑2 cross‑linked on collagen discs following subcutaneous implantation in rats were evaluated. Independent two‑tailed t‑tests and one‑way analysis of variance were used for analysis. In the present study, the controlled release of SDF‑1α chemically conjugated on collagen scaffolds was demonstrated. By optimizing the concentrations of Traut's reagent and the Sulfo‑SMCC cross‑linker, a significantly higher level of SDF‑1α was covalently retained on the collagen scaffold, compared with that retained using a physical adsorption method. Mesenchymal stem cell homing indicated that the biological function of the SDF‑1α cross‑linked on the collagen scaffolds remained intact. In rats, co‑treatment with SDF‑1α and a suboptimal dose of BMP‑2 cross‑linked on collagen scaffolds using this chemically conjugated method induced higher levels of ectopic bone formation, compared with the physical adsorption method. No ectopic bone formation was observed following treatment with a suboptimal dose of BMP‑2 alone. Therefore, the co‑delivery of SDF‑1α and a suboptimal dose of BMP‑2 chemically conjugated on collagen scaffolds for the treatment of bone injuries reduced the level of BMP‑2 required, reducing the risks of side effects.
authors.affiliation: Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oral Implantology, Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002113:Calcification, Physiologic / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000008:administration & dosage*; D003094:Collagen; D003692:Delayed-Action Preparations; D007279:Injections, Subcutaneous; D007700:Kinetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D054457:Tissue Scaffolds
chemical_list: D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D003692:Delayed-Action Preparations; D003094:Collagen