Advanced Healthcare Materials
·
2022
·Vol. 11
·期 10
·2101983
·
IF 11.092
Miusi Shi,Wenting Mo,Haoning Qi,Yueqi Ni,Rui Wang,Kailun Shen,Fanyu Zhang,Shuting Jiang,Xuehui Zhang,Lili Chen,Yufeng Zhang,Xuliang Deng
Mechanistic understanding of fibronectin (FN) adsorption which determines cell adhesion on cell–implant interfaces is significant for improving the osteoconduction and soft-tissue healing of implants. Here, it is shown that the adsorption behavior of FN on the titanium oxide surface (TiO 2 ) is highly relative to its Pro-His-Ser-Arg-Asn (PHSRN) peptide. FN lacking PHSRN fails to bind to surfaces, resulting in inhibited cell adhesion and spreading. Molecular dynamics simulation shows higher affinity and greater adsorption energy of PHSRN peptide with TiO 2 surface due to the stronger hydrogen bonds formed by the serine and arginine residues with O ion of the substrate. Finally, by increasing O content in TiO 2 surfaces through O ion-beam implantation, improving the cell adhesion, cell differentiation, and the subsequent biomineralization on titanium implant is realized. This study reveals the vital role of PHSRN in FN-mediated cell adhesion on implant surfaces, providing a promising new target for further tissue integration and implant success.
研究领域:
生物材料
·
细胞生物学
·
表面科学
·
组织工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 12
·2100028
·
IF 9.933
Hang Yang,Yan Luo,Hang Hu,Sibo Yang,Yanan Li,Huijuan Jin,Shengcai Chen,Quanwei He,Candong Hong,Jiehong Wu,Yan Wan,Man Li,Zifu Li,Xiangliang Yang,Ying Su,Yifan Zhou,Bo Hu
Angiogenesis, an essential restorative process following ischemia, is a promising therapeutic approach to improve neurological deficits. However, overcoming the blood–brain barrier (BBB) and effective drug enrichment are challenges for conventional drug delivery methods, which has limited the development of treatment strategies. Herein, a dual-targeted therapeutic strategy is reported to enable pH-sensitive drug release and allow cerebral ischemia targeting to improve stroke therapeutic efficacy. Targeted delivery is achieved by surface conjugation of Pro-His-Ser-Arg-Asn (PHSRN) peptides, which binds to integrin α 5 β 1 enriched in the cerebral vasculature of ischemic tissue. Subsequently, smoothened agonist (SAG), an activator of sonic hedgehog (Shh) signaling, is coupled to PHSRN-HES by pH-dependent electrostatic adsorption. SAG@PHSRN-HES nanoparticles can sensitively release more SAG in the acidic environment of ischemic brain tissue. More importantly, SAG@PHSRN-HES exerts the synergistic mechanisms of PHSRN and SAG to promote angiogenesis and BBB integrity, thus improving neuroplasticity and neurological function recovery. This study proposes a new approach to improve the delivery of medications in the ischemic brain. Dual-targeted therapeutic strategies have excellent potential to treat patients suffering from cerebral infarction.
研究领域:
神经科学
·
药学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Lijing Hao,Tianjie Li,Lin Wang,Xuetao Shi,Yan Fan,Chang Du,Yingjun Wang
Fibronectin (Fn) is significant to the performance of biomaterials, and the chemistry of biomaterial surface play important roles in Fn adsorption and subsequent cell behavior. However, the “molecular scale” mechanism is still unclear. Herein, we combined experimental strategies with molecular simulations to solve this problem. We prepared self-assembled monolayers with varying chemistries, i.e., SAMs-CH 3 , SAMs-NH 2 , SAMs-COOH and SAMs-OH, and characterized Fn adsorption and cell behaviors on them. Next, Monte Carlo method and all-atom molecular dynamics simulations were employed to reveal the orientation/conformation of Fn on surfaces. We found that SAMs-CH 3 strongly adsorbed Fn via hydrophobic interactions, but show poor bioactivity as the low exposure of RGD/PHSRN motifs and the deformation of Fn. SAMs-NH 2 and SAMs-COOH could adsorb Fn efficiently via vdW interactions, electrostatic interactions, hydrogen bonds and salt bridges. Fn exhibited excellent bioactivity for cell adhesion, proliferation and osteogenic differentiation as high exposure of bioactive motifs on SAMs-NH 2 , or as the activation of other inferior cell-binding motifs on SAMs-COOH. SAMs-OH showed poor Fn adsorption as the water film. However, the adsorbed Fn displayed non-negligible bioactivity due to high exposure of PHSRN motif and large degree of protein flexibility. We believe that the revealed mechanism presents great potential to rationally design Fn-activating biomaterials.
研究领域:
生物材料
·
分子生物学
·
细胞生物学
·
表面化学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）