Reinforcement of epithelial sealing around titanium dental implants by chimeric peptides

Liu, Zihao; Ma, Shiqing; Lü, Xin; Zhang, Tao; Sun, Yingchun; Feng, Wei; Zheng, Gen; Sui, Lei; Wu, Xudong; Zhang, Xu; Gao, Ping

doi:10.1016/j.cej.2018.09.004

Cited by 31 publications

(29 citation statements)

References 60 publications

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“…Previously, scholars have focused on improving epithelial biological sealing around implants and HD formation by coating titanium surfaces with LM332 or LM332-derived peptides. 14 , 15 , 16 , 17 , 18 However, exogenous LM332, as a macromolecular protein, can cause immune rejection in the body and rapid protein degradation. Furthermore, protein synthesis can be expensive and suboptimal for clinical application.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-Mediated LAMA3 Transduction Enhances Hemidesmosome Formation and Periodontal Reattachment during Wound Healing

Zhang

Zhen-xuan

et al. 2020

Molecular Therapy - Methods & Clinical Development

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A robust dento-epithelial junction prevents external pathogenic factors from entering connective tissue and could be crucial for periodontal reattachment after periodontal surgery. The junctional epithelium (JE) is attached to the tooth surface through the hemidesmosome (HD) and internal basal lamina, where the primary component is laminin-332. Destruction of the JE leads to the loss of periodontal attachment. Traditional treatments are effective in eliminating local inflammation of the gingiva; however, few directly promote periodontal reattachment and HD formation. Here, we designed a gene-therapy strategy using the adenovirus-mediated human laminin-332 α3 chain (LAMA3) gene (Ad-LAMA3) transduced into a human-immortalized epidermal cell line (HaCaT) to study the formation of HD in vitro . Ad-LAMA3 promoted early adhesion and fast migration of HaCaT cells and increased expression of LAMA3 and type XVII collagen (BP180) significantly. Furthermore, HaCaT cells could facilitate formation of mature HDs after LAMA3 overexpression. In vivo experiments demonstrated that the JE transduced with Ad-LAMA3 could increase expression of LAMA3 and BP180 and “biological sealing” between the tooth and gingival epithelium. These results suggested that adenovirus-mediated LAMA3 transduction is a novel therapeutic strategy that promotes the stability and integration of the JE around the tooth during wound healing.

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Section: Introductionmentioning

confidence: 99%

Adenovirus-Mediated LAMA3 Transduction Enhances Hemidesmosome Formation and Periodontal Reattachment during Wound Healing

Zhang

Zhen-xuan

et al. 2020

Molecular Therapy - Methods & Clinical Development

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“…This novel GSGGG spacer showed enhanced antimicrobial activity compared to the classic spacer we used here [ 57 , 58 ]. Other work has compared a rigid spacer [(EAAAK) 4 ] against a flexible spacer [(GGGGS) 4 ]; the flexible spacer design showed more effective eukaryotic cell signaling but less effective antimicrobial activity [ 36 , 59 ]. Others have shown that flexibility per se is not the requisite design criteria but rather matching hydrophobicity/philicity of surrounding residues leads to maximal eukaryotic response [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…Other biomedical devices suffer a similar fate [ 32 ]; implantable auditory assist devices demonstrate a 26% failure rate [ 33 ] and infections occur in up to 77% of individuals with bone-anchored orthopaedic devices [ 34 ]. We have selected the peptide LamLG3 identified [ 35 ] from a globular module (LG3) of laminin332 (LM332) capable of inducing hemidesmosome (HD) formation from oral keratinocytes in the soft tissue surrounding dental implants [ 5 , 36 , 37 ]. HDs are a transmembrane “link” or “rivet” between teeth and gingiva ( Figure 1 ), as the gingiva forms a protective, physical barrier for the tooth, or dental implant, against biofilm invasion [ 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Surface Immobilization Chemistry of a Laminin-Derived Peptide Affects Keratinocyte Activity

Fischer

Aparicio

2020

Coatings

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Many chemical routes have been proposed to immobilize peptides on biomedical device surfaces, and in particular, on dental implants to prevent peri-implantitis. While a number of factors affect peptide immobilization quality, an easily controllable factor is the chemistry used to immobilize peptides. These factors affect peptide chemoselectivity, orientation, etc., and ultimately control biological activity. Using many different physical and chemical routes for peptide coatings, previous research has intensely focused on immobilizing antimicrobial elements on dental implants to reduce infection rates. Alternatively, our strategy here is different and focused on promoting formation of a long-lasting biological seal between the soft tissue and the implant surface through transmembrane, cell adhesion structures called hemidesmosomes. For that purpose, we used a laminin-derived call adhesion peptide. However, the effect of different immobilization chemistries on cell adhesion peptide activity is vastly unexplored but likely critical. Here, we compared the physiochemical properties and biological responses of a hemidesmosome promoting peptide immobilized using silanization and copper-free click chemistry as a model system for cell adhesion peptides. Successful immobilization was confirmed with water contact angle and X-ray photoelectron spectroscopy. Peptide coatings were retained through 73 days of incubation in artificial saliva. Interestingly, the non-chemoselective immobilization route, silanization, resulted in significantly higher proliferation and hemidesmosome formation in oral keratinocytes compared to chemoselective click chemistry. Our results highlight that the most effective immobilization chemistry for optimal peptide activity is dependent on the specific system (substrate/peptide/cell/biological activity) under study. Overall, a better understanding of the effects immobilization chemistries have on cell adhesion peptide activity may lead to more efficacious coatings for biomedical devices.

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“…The G domain located at the C-terminal end of the α3 chain contains five repeating LG domains (LG1-5), among which, LG1-3 interacts with the α3β1, α6β1, and α6β4 integrins, while LG4 and LG5 combine with syndecan-1 and -4 (Rousselle et al, 2019). Liu et al (2019) successfully used Ti modification with chimeric peptideschimeric peptides (derived from the LG3 domain of the α3 chain of laminin332) to improve epithelial sealing on Ti surfaces with the potential to prevent perimucositis and peri-implantitis. In the study, the G domain of α3 chain of laminin332 was selected as the functional section, which plays an important role in the formation of HDs.…”

Section: Discussionmentioning

confidence: 99%

Surfce Functionalized via AdLAMA3 Multilayer Coating for Re-epithelization Around Titanium Implants

Zhang

et al. 2020

Front. Bioeng. Biotechnol.

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The peri-implant epithelium (PIE) forms a crucial seal between the oral environment and the implant surface. Compared with the junctional epithelium (JE), the biological sealing of PIE is fragile, which lacks hemidesmosomes (HDs) and internal basal lamina (extracellular matrix containing laminin332, IBL) on the upper part of the interface. In the study, we aim to prepare a coating with good biocompatibility and ability to immobilize the recombinant adenovirus vector of LAMA3 (AdLAMA3) for promoting the re-epithelization of PIE. The titanium surface functionalized with AdLAMA3 was established via layer-by-layer assembly technique and antibody-antigen specific binding. The biological evaluations including cell adhesion and the re-epithelization of PIE were investigated. The results in vitro demonstrated that the AdLAMA3 coating could improve epithelial cell attachment and cell spreading in the early stage. In vivo experiments indicated that the AdLAMA3 coating on the implant surface has the potential to accelerate the healing of the PIE, and could promote the expression of laminin α3 and the formation of hemidesmosomes. This study might provide a novel approach and experimental evidence for the precise attachment of LAMA3 to titanium surfaces. The process could improve the re-epithelization of PIE.

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Reinforcement of epithelial sealing around titanium dental implants by chimeric peptides

Cited by 31 publications

References 60 publications

Adenovirus-Mediated LAMA3 Transduction Enhances Hemidesmosome Formation and Periodontal Reattachment during Wound Healing

Adenovirus-Mediated LAMA3 Transduction Enhances Hemidesmosome Formation and Periodontal Reattachment during Wound Healing

Surface Immobilization Chemistry of a Laminin-Derived Peptide Affects Keratinocyte Activity

Surfce Functionalized via AdLAMA3 Multilayer Coating for Re-epithelization Around Titanium Implants

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