Fusion peptide engineered “statically-versatile” titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration

Chen, Junjian; Hu, Guoqing; Li, Tianjie; Chen, Yunhua; Gao, Meng; Li, Qingtao; Li, Hao; Jia, Yong‐Guang; Wang, Lin; Wang, Yingjun

doi:10.1016/j.biomaterials.2020.120446

Cited by 56 publications

(39 citation statements)

References 83 publications

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“…There was no significant difference ( p > 0.05) in cell proliferation activity between the composite group and the control group in different time points. However, many studies have shown the potential cytotoxicity of the HHC36 at high concentration on stem cells ( Chen et al, 2020 ; Chen et al, 2021 ). It indicated that the sustained release effect of HA MSs with hierarchical structure on HHC36 effectively decreased the cytotoxicity to stem cells, which further illustrated the potential applications of composite microspheres in bone tissue engineering.…”

Section: Resultsmentioning

confidence: 99%

“…The covalent modification of AMPs on substrate materials is a common strategy for local delivery ( Boden et al, 2018 ; Chouirfa et al, 2019 ; Acosta et al, 2020 ). This method requires relatively complicated processing steps, which may bring about changes in the primary and/or secondary structure of AMPs ( Chen et al, 2021 ). Moreover, the covalently immobilized AMPs have poor stability to enzymes and low activity against the inaccessible bacteria in surrounding tissues ( Aveyard et al, 2017 ; De Zoysa and Sarojini, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial Peptides-Loaded Hydroxyapatite Microsphere With Different Hierarchical Structures for Enhanced Drug Loading, Sustained Release and Antibacterial Activity

Hong

Xiao

et al. 2021

Front. Chem.

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Antimicrobial peptides (AMPs) have great potential for clinical treatment of bacterial infection due to the broad-spectrum and highly effective antibacterial activity. However, the easy degradation and inactivation in vivo has been a major obstacle for their application and an effective delivery system is demanding. The surface physicochemical properties of the carrier, including surface potential, surface polarity, pore structure and morphology, have exerted great effects on the adsorption and release behavior of AMPs. This study investigated the influence of micro/nano carriers with different hierarchical structures on the loading, release and biological behavior of AMPs. Three types of AMPs-loaded hydroxyapatite microspheres (HA/AMPs MSs) with different hierarchical structures (needle-like, rod-like, and flake-like) were developed, which was investigated by the surface morphology, chemical composition and surface potential in detail. The different hierarchical structures of hydroxyapatite microspheres (HA MSs) had noticeable impact on the loading and release behavior of AMPs, and the flake-like HA MSs with hierarchical structure showed the highest loading efficiency and long-lasting release over 9 days. Meanwhile, the stability of AMPs released from HA MSs was effectively maintained. Moreover, the antibacterial test indicated that the flake-like HA/AMPs MSs showed more sustained antibacterial properties among three composites. In view of the excellent biocompatibility and osteogenic property, high loading efficiency and the long-term release properties of HA MSs with hierarchical structure, the HA/AMPs MSs have a great potential in bone tissue engineering.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptides-Loaded Hydroxyapatite Microsphere With Different Hierarchical Structures for Enhanced Drug Loading, Sustained Release and Antibacterial Activity

Hong

Xiao

et al. 2021

Front. Chem.

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“…Since then, the QK peptide has been used in many studies to improve angiogenic properties of different implant materials. For instance, Chen and colleagues demonstrated that QK immobilized on titanium implants showed even antimicrobial effects and promoted vascularization and osseointegration in an in vivo animal model [42].…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Potential of VEGF Mimetic Peptides for the Biofunctionalization of Collagen/Hydroxyapatite Composites

et al. 2021

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Currently, the focus on bioinspired concepts for the development of tissue engineering constructs is increasing. For this purpose, the combination of collagen (Coll) and hydroxyapatite (HA) comes closest to the natural composition of the bone. In order to confer angiogenic properties to the scaffold material, vascular endothelial growth factor (VEGF) is frequently used. In the present study, we used a VEGF mimetic peptide (QK) and a modified QK-peptide with a poly-glutamic acid tag (E7-QK) to enhance binding to HA, and analyzed in detail binding efficiency and angiogenic properties. We detected a significantly higher binding efficiency of E7-QK peptides to hydroxyapatite particles compared to the unmodified QK-peptide. Tube formation assays revealed similar angiogenic functions of E7-QK peptide (1µM) as induced by the entire VEGF protein. Analyses of gene expression of angiogenic factors and their receptors (FLT-1, KDR, HGF, MET, IL-8, HIF-1α, MMP-1, IGFBP-1, IGFBP-2, VCAM-1, and ANGPT-1) showed higher expression levels in HUVECs cultured in the presence of 1µM E7-QK and VEGF compared to those detected in the negative control group without any angiogenic stimuli. In contrast, the expression of the anti-angiogenic gene TIMP-1 showed lower mRNA levels in HUVECs cultured with E7-QK and VEGF. Sprouting assays with HUVEC spheroids within Coll/HA/E7-QK scaffolds showed significantly longer sprouts compared to those induced within Coll/HA/QK or Coll/HA scaffolds. Our results demonstrate a significantly better functionality of the E7-QK peptide, electrostatically bound to hydroxyapatite particles compared to that of unmodified QK peptide. We conclude that the used E7-QK peptide represents an excellently suited biomolecule for the generation of collagen/hydroxyapatite composites with angiogenic properties.

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“…We further detected the promotion effect of the coating on early and late osteogenic differentiation by ALP staining, alizarin red staining, and qRT-PCR. High expression of ALP is essential for the degradation of pyrophosphate in the early stage of osteogenic differentiation, an inhibitor of mineralization ( Jablonská et al, 2020 ; Oh et al, 2020 ; Tao et al, 2020 ; Chen et al, 2021b ). Therefore, rational morphology HA coatings and a low degree of crystalline formation of PS could enhance the osteogenic differentiation of BMSCs at the early stage.…”

Section: Discussionmentioning

confidence: 99%

Plasma Spray vs. Electrochemical Deposition: Toward a Better Osteogenic Effect of Hydroxyapatite Coatings on 3D-Printed Titanium Scaffolds

Sun

Zhang

Luo

et al. 2021

Front. Bioeng. Biotechnol.

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Surface modification of three-dimensional (3D)-printed titanium (Ti) scaffolds with hydroxyapatite (HA) has been a research hotspot in biomedical engineering. However, unlike HA coatings on a plain surface, 3D-printed Ti scaffolds have inherent porous structures that influence the characteristics of HA coatings and osteointegration. In the present study, HA coatings were successfully fabricated on 3D-printed Ti scaffolds using plasma spray and electrochemical deposition, named plasma sprayed HA (PSHA) and electrochemically deposited HA (EDHA), respectively. Compared to EDHA scaffolds, HA coatings on PSHA scaffolds were smooth and continuous. In vitro cell studies confirmed that PSHA scaffolds have better potential to promote bone mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation than EDHA scaffolds in the early and late stages. Moreover, in vivo studies showed that PSHA scaffolds were endowed with superior bone repair capacity. Although the EDHA technology is simpler and more controllable, its limitation due to the crystalline and HA structures needs to be improved in the future. Thus, we believe that plasma spray is a better choice for fabricating HA coatings on implanted scaffolds, which may become a promising method for treating bone defects.

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Fusion peptide engineered “statically-versatile” titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration

Cited by 56 publications

References 83 publications

Antimicrobial Peptides-Loaded Hydroxyapatite Microsphere With Different Hierarchical Structures for Enhanced Drug Loading, Sustained Release and Antibacterial Activity

Antimicrobial Peptides-Loaded Hydroxyapatite Microsphere With Different Hierarchical Structures for Enhanced Drug Loading, Sustained Release and Antibacterial Activity

Angiogenic Potential of VEGF Mimetic Peptides for the Biofunctionalization of Collagen/Hydroxyapatite Composites

Plasma Spray vs. Electrochemical Deposition: Toward a Better Osteogenic Effect of Hydroxyapatite Coatings on 3D-Printed Titanium Scaffolds

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