PMID- 29340375 OWN - NLM STAT- MEDLINE DCOM- 20180803 LR - 20181202 IS - 2047-4849 (Electronic) IS - 2047-4830 (Linking) VI - 6 IP - 2 DP - 2018 Jan 30 TI - Enhancement of BMP-2-mediated angiogenesis and osteogenesis by 2-N,6-O-sulfated chitosan in bone regeneration. PG - 431-439 LID - 10.1039/c7bm01006k [doi] AB - Sulfated polysaccharides are attractive semi-synthesized materials that can be used as a mimic of heparan sulfate to modulate the protein activity and other physiological processes. In this study, we employed sulfated chitosan to enhance the angiogenic capacity of bone morphogenic protein-2 (BMP-2). Bone marrow stromal cells (BMSCs) cultured in a combination of BMP-2 and 2-N,6-O-sulfated chitosan (SCS) group exhibited a higher cell viability and sprouting ability. The cells also secreted more VEGF and NO. The expression patterns of angiogenic and osteogenic genes were analyzed, and VEGFR2 signaling was found to play a role in the enhancing effect of SCS. The chick embryo chorioallantoic membrane (CAM) assay revealed an enhanced angiogenic effect of BMP-2 when SCS was involved. In addition, we investigated angiogenesis and osteogenesis in mouse using a BMP-2-induced ectopic bone model. Histological and immune-staining analysis revealed that both bone and vascular tissue were enhanced when SCS was added. These data prove that SCS can improve the angiogenic potential of BMP-2 and thus lead to better bone regeneration. FAU - Pan, Yuanzhong AU - Pan Y AD - The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237 People's Republic of China. biomatwj@163.com liucs@ecust.edu.cn. FAU - Chen, Jie AU - Chen J FAU - Yu, Yuanman AU - Yu Y FAU - Dai, Kai AU - Dai K FAU - Wang, Jing AU - Wang J FAU - Liu, Changsheng AU - Liu C LA - eng PT - Journal Article PL - England TA - Biomater Sci JT - Biomaterials science JID - 101593571 RN - 0 (2-N, 6-O-sulfated chitosan) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Vascular Endothelial Growth Factor A) RN - 31C4KY9ESH (Nitric Oxide) RN - 9012-76-4 (Chitosan) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology/drug effects/metabolism MH - Bone Morphogenetic Protein 2/*pharmacology MH - *Bone Regeneration MH - Cells, Cultured MH - Chick Embryo MH - Chitosan/*analogs & derivatives/pharmacology MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Mice MH - *Neovascularization, Physiologic MH - Nitric Oxide/metabolism MH - *Osteogenesis MH - Rats MH - Rats, Sprague-Dawley MH - Vascular Endothelial Growth Factor A/metabolism EDAT- 2018/01/18 06:00 MHDA- 2018/08/04 06:00 CRDT- 2018/01/18 06:00 PHST- 2018/01/18 06:00 [pubmed] PHST- 2018/08/04 06:00 [medline] PHST- 2018/01/18 06:00 [entrez] AID - 10.1039/c7bm01006k [doi] PST - ppublish SO - Biomater Sci. 2018 Jan 30;6(2):431-439. doi: 10.1039/c7bm01006k.