Biomimetic Strategy to Enhance Epithelial Cell Viability and Spreading on PEEK Implants.

Polyetheretherketone (PEEK) is a biocompatible material widely used in spinal and craniofacial implants, with potential use in percutaneous implants. However, its inertness prevents it from forming a tight seal with the surrounding soft tissue, which can lead to infections and implant failure. Conversely, the surface chemistry of percutaneous organs (i.e., teeth) helps establish a strong interaction with the epithelial cells of the contacting soft tissues, and hence a tight seal, preventing infection. The seal is created by adsorption of basement membrane (BM) proteins, secreted by epithelial cells, onto the percutaneous organ surfaces. Here, we aim to create a tight seal between PEEK and epithelial tissues by mimicking the surface chemistry of teeth. Our hypothesis is that collagen I, the most abundant tooth protein, enables integration between the epithelial tissue and teeth by promoting adsorption of BM proteins. To test this, we immobilized collagen I via EDC/NHS coupling on a carboxylated PEEK surface modified using diazonium chemistry. We used titanium alloy (Ti-6Al-4V) for comparison, as titanium is the most widely used percutaneous biomaterial. Both collagen-modified PEEK and titanium showed a larger adsorption of key BM proteins (laminin, nidogen, and fibronectin) compared to controls. Keratinocyte epithelial cell viability on collagen-modified PEEK was twice that of control PEEK and ∼1.5 times that of control titanium after 3 days of cell seeding. Both keratinocytes and fibroblasts spread more on collagen-modified PEEK and titanium compared to controls. This work introduces a versatile and biomimetic surface modification technique that may enhance PEEK-epithelial tissue sealing with the potential of extending PEEK applications to percutaneous implants, making it competitive with titanium.

[1]  Lingzhou Zhao,et al.  Laminin 332-functionalized coating to regulate the behavior of keratinocytes and gingival mesenchymal stem cells to enhance implant soft tissue sealing , 2022, Regenerative biomaterials.

[2]  C. Simmons,et al.  An SCPPPQ1/LAM332 protein complex enhances the adhesion and migration of oral epithelial cells: Implications for dentogingival regeneration. , 2022, Acta biomaterialia.

[3]  N. Enkling,et al.  Soft tissue response to different abutment materials: A controlled and randomized human study using an experimental model. , 2022, Clinical oral implants research.

[4]  C. Aparicio,et al.  Tapping Basement Membrane Motifs: Oral Junctional Epithelium for Surface-mediated Soft Tissue Attachment to Prevent Failure of Percutaneous Devices. , 2021, Acta biomaterialia.

[5]  A. Passaniti,et al.  Matrigel: history/background, uses, and future applications , 2021, Journal of cell communication and signaling.

[6]  Jie Wei,et al.  Fabrication of Submicro-Nano Structures on Polyetheretherketone Surface by Femtosecond Laser for Exciting Cellular Responses of MC3T3-E1 Cells/Gingival Epithelial Cells , 2021, International journal of nanomedicine.

[7]  L. Stone,et al.  Protein Adsorption on Surfaces Functionalized with COOH Groups Promotes Anti-inflammatory Macrophage Responses. , 2021, ACS applied materials & interfaces.

[8]  K. Gulati,et al.  Orchestrating Soft Tissue Integration at the Transmucosal Region of Titanium Implants. , 2021, Acta biomaterialia.

[9]  N. Huang,et al.  Polydopamine (PDA) mediated nanogranular-structured titanium dioxide (TiO2) coating on polyetheretherketone (PEEK) for oral and maxillofacial implants application , 2020 .

[10]  Yi Deng,et al.  Multifunctional Surface with Enhanced Angiogenesis for Improving Long-Term Osteogenic Fixation of Polyetheretherketone Implants. , 2020, ACS applied materials & interfaces.

[11]  K. Koyano,et al.  Effect of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning. , 2020, Journal of oral science.

[12]  M. Cerruti,et al.  Surface Modification Strategies to Improve the Osseointegration of Poly(etheretherketone) and Its Composites. , 2019, Macromolecular bioscience.

[13]  M. Laurenti,et al.  Biocompatibility and Durability of Diazonium Adhesives on Dental Alloys. , 2019, Journal of prosthodontics : official journal of the American College of Prosthodontists.

[14]  D. Buser,et al.  Soft tissue response to dental implant closure caps made of either polyetheretherketone (PEEK) or titanium. , 2019, Clinical oral implants research.

[15]  Zhe Cao,et al.  A Facile Surface Modification Method for Synergistically Enhancing Biocompatibility and Bioactivity of Polyetheretherketone with Inducing Osteo-differentiation. , 2019, ACS applied materials & interfaces.

[16]  Jiandong Ding,et al.  Polydopamine-mediated covalent functionalization of collagen on a titanium alloy to promote biocompatibility with soft tissues. , 2019, Journal of materials chemistry. B.

[17]  Truc Thi Hoang Nguyen,et al.  General review of titanium toxicity , 2019, International Journal of Implant Dentistry.

[18]  S. Mishra,et al.  PEEK materials as an alternative to titanium in dental implants: A systematic review , 2018, Clinical implant dentistry and related research.

[19]  Zhenjie Sun,et al.  Controllable and durable release of BMP-2-loaded 3D porous sulfonated polyetheretherketone (PEEK) for osteogenic activity enhancement. , 2018, Colloids and surfaces. B, Biointerfaces.

[20]  C. Aparicio,et al.  Peptide coatings enhance keratinocyte attachment towards improving the peri-implant mucosal seal. , 2018, Biomaterials science.

[21]  Yizhi Xiao,et al.  Comparative adsorption profiles of basal lamina proteome and gingival cells onto dental and titanium surfaces. , 2018, Acta biomaterialia.

[22]  P. Habibović,et al.  Understanding interactions between biomaterials and biological systems using proteomics. , 2018, Biomaterials.

[23]  H. Meng,et al.  Influence on proliferation and adhesion of human gingival fibroblasts from different titanium surface decontamination treatments: An in vitro study. , 2018, Archives of oral biology.

[24]  I. Kang,et al.  Enhanced Tissue Compatibility of Polyetheretherketone Disks by Dopamine-Mediated Protein Immobilization , 2018, Macromolecular Research.

[25]  R. Daza,et al.  Enhanced Biological Response of AVS-Functionalized Ti-6Al-4V Alloy through Covalent Immobilization of Collagen , 2018, Scientific Reports.

[26]  S. Ivanovski,et al.  Comparison of peri‐implant and periodontal marginal soft tissues in health and disease , 2018, Periodontology 2000.

[27]  O. Kharbanda,et al.  Bio-functionalization of grade V titanium alloy with type I human collagen for enhancing and promoting human periodontal fibroblast cell adhesion - an in-vitro study. , 2018, Colloids and surfaces. B, Biointerfaces.

[28]  R. Guldberg,et al.  Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody Fusion Devices , 2017, Techniques in orthopaedics.

[29]  N. Lang,et al.  Marginal healing using Polyetheretherketone as healing abutments: an experimental study in dogs , 2017, Clinical oral implants research.

[30]  M. Laurenti,et al.  Biomaterial surface proteomic signature determines interaction with epithelial cells. , 2017, Acta biomaterialia.

[31]  M. Gurruchaga,et al.  Proteome analysis of human serum proteins adsorbed onto different titanium surfaces used in dental implants , 2017, Biofouling.

[32]  Chris Peach,et al.  Topology Optimization to reduce the stress shielding effect for orthopedic applications , 2017 .

[33]  R. Farivar,et al.  Surface phosphonation enhances hydroxyapatite coating adhesion on polyetheretherketone and its osseointegration potential. , 2017, Acta biomaterialia.

[34]  H. Sorg,et al.  Skin Wound Healing: An Update on the Current Knowledge and Concepts , 2016, European Surgical Research.

[35]  W. Walsh,et al.  Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model? , 2016, Clinical orthopaedics and related research.

[36]  R. Langer,et al.  Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6bm00214e Click here for additional data file. , 2016, Biomaterials science.

[37]  T. Kamarul,et al.  Preparation Methods for Improving PEEK's Bioactivity for Orthopedic and Dental Application: A Review , 2016, International journal of biomaterials.

[38]  Meriem Lamghari,et al.  The two faces of metal ions: From implants rejection to tissue repair/regeneration. , 2016, Biomaterials.

[39]  Xiaodong Wu,et al.  Covalently immobilised type I collagen facilitates osteoconduction and osseointegration of titanium coated implants , 2015, Journal of orthopaedic translation.

[40]  R. Gauvin,et al.  Hydroxyapatite formation on graphene oxide modified with amino acids: arginine versus glutamic acid , 2016, Journal of The Royal Society Interface.

[41]  U. Ritz,et al.  The effect of different collagen modifications for titanium and titanium nitrite surfaces on functions of gingival fibroblasts , 2016, Clinical Oral Investigations.

[42]  P. Lipp,et al.  Differential Behavior of Fibroblasts and Epithelial Cells on Structured Implant Abutment Materials: A Comparison of Materials and Surface Topographies. , 2015, Clinical implant dentistry and related research.

[43]  Sunarso,et al.  Modulation of the osteoconductive property and immune response of poly(ether ether ketone) by modification with calcium ions. , 2015, Journal of materials chemistry. B.

[44]  M. Salmerón-Sánchez,et al.  Different Organization of Type I Collagen Immobilized on Silanized and Nonsilanized Titanium Surfaces Affects Fibroblast Adhesion and Fibronectin Secretion. , 2015, ACS applied materials & interfaces.

[45]  K. Koyano,et al.  Effects of CaCl2 hydrothermal treatment of titanium implant surfaces on early epithelial sealing. , 2015, Colloids and surfaces. B, Biointerfaces.

[46]  A. Wennerberg,et al.  Nanosized Hydroxyapatite Coating on PEEK Implants Enhances Early Bone Formation: A Histological and Three-Dimensional Investigation in Rabbit Bone , 2015, Materials.

[47]  S. Rimpelová,et al.  Tailoring of PEEK bioactivity for improved cell interaction: plasma treatment in action , 2015 .

[48]  H. Nie,et al.  In vitro and in vivo evaluation of bone morphogenetic protein-2 (BMP-2) immobilized collagen-coated polyetheretherketone (PEEK) , 2015, Frontiers of Materials Science.

[49]  Yizhi Xiao,et al.  Proteomic Signature of the Murine Intervertebral Disc , 2015, PloS one.

[50]  H. Kleinman,et al.  Matrigel: from discovery and ECM mimicry to assays and models for cancer research. , 2014, Advanced drug delivery reviews.

[51]  C. Aparicio,et al.  Collagen-functionalised titanium surfaces for biological sealing of dental implants: effect of immobilisation process on fibroblasts response. , 2014, Colloids and surfaces. B, Biointerfaces.

[52]  Yanyan Zheng,et al.  Formation of bone-like apatite on plasma-carboxylated poly(etheretherketone) surface , 2014 .

[53]  E. Dumas,et al.  Fabrication and characterization of all-covalent nanocomposite functionalized screen-printed voltammetric sensors , 2014 .

[54]  B. Boyan,et al.  A review on the wettability of dental implant surfaces II: Biological and clinical aspects. , 2014, Acta biomaterialia.

[55]  Yijin Ren,et al.  Soft tissue integration versus early biofilm formation on different dental implant materials. , 2014, Dental materials : official publication of the Academy of Dental Materials.

[56]  J. Kinsella,et al.  Surface modification of poly(D,L-lactic acid) scaffolds for orthopedic applications: a biocompatible, nondestructive route via diazonium chemistry. , 2014, ACS applied materials & interfaces.

[57]  J. Ong,et al.  Current trends in dental implants , 2014, Journal of the Korean Association of Oral and Maxillofacial Surgeons.

[58]  Xiaohua Yu,et al.  Covalent Immobilization of Collagen on Titanium through Polydopamine Coating to Improve Cellular Performances of MC3T3-E1 Cells. , 2014, RSC advances.

[59]  E. Adolfsson,et al.  Phase Stability and Mechanical Properties of Zirconia and Zirconia Composites , 2013 .

[60]  Quanli Li,et al.  Biocompatibility studies of poly(ethylene glycol)–modified titanium for cardiovascular devices , 2012 .

[61]  W. Att,et al.  Zirconia in fixed implant prosthodontics. , 2012, Clinical implant dentistry and related research.

[62]  Sonny B. Bal,et al.  Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium , 2012, International journal of nanomedicine.

[63]  L. Bertassoni,et al.  The dentin organic matrix – limitations of restorative dentistry hidden on the nanometer scale , 2012, Acta biomaterialia.

[64]  M. Grinstaff,et al.  Biocompatible and bioactive surface modifications for prolonged in vivo efficacy. , 2012, Chemical reviews.

[65]  A. Leask,et al.  Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair? , 2011, PloS one.

[66]  P. Vermette,et al.  Bridging the gap between physicochemistry and interpretation prevalent in cell-surface interactions. , 2011, Chemical reviews.

[67]  C. Murray,et al.  A review of dental implants and infection. , 2009, The Journal of hospital infection.

[68]  A. Singh,et al.  Ti based biomaterials, the ultimate choice for orthopaedic implants – A review , 2009 .

[69]  D. Vautier,et al.  The effect of microstructured surfaces and laminin-derived peptide coatings on soft tissue interactions with titanium dental implants. , 2009, Biomaterials.

[70]  S. Noël,et al.  Covalent grafting onto self-adhesive surfaces based on aryldiazonium salt seed layers , 2008 .

[71]  M. Niinomi Biologically and Mechanically Biocompatible Titanium Alloys , 2008 .

[72]  Peter C. St. John,et al.  Modification of silk fibroin using diazonium coupling chemistry and the effects on hMSC proliferation and differentiation. , 2008, Biomaterials.

[73]  H. Mobley,et al.  Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis , 2008, Clinical Microbiology Reviews.

[74]  G W Blunn,et al.  Fibronectin silanized titanium alloy: a bioinductive and durable coating to enhance fibroblast attachment in vitro. , 2007, Journal of biomedical materials research. Part A.

[75]  S. Kurtz,et al.  PEEK biomaterials in trauma, orthopedic, and spinal implants. , 2007, Biomaterials.

[76]  J. Pinson,et al.  Surface Modification of Conducting Substrates. Existence of Azo Bonds in the Structure of Organic Layers Obtained from Diazonium Salts , 2007 .

[77]  V. Wilson,et al.  In vitro culture conditions to study keratinocyte differentiation using the HaCaT cell line , 2007, Cytotechnology.

[78]  Philip J. Rae,et al.  The mechanical properties of poly(ether-ether-ketone) (PEEK) with emphasis on the large compressive strain response , 2007 .

[79]  C. M. Lilley,et al.  Surface contamination effects on resistance of gold nanowires , 2006 .

[80]  Kenneth M. Yamada,et al.  The matrix reorganized: extracellular matrix remodeling and integrin signaling. , 2006, Current opinion in cell biology.

[81]  B. Sumpter,et al.  Structure and bonding between an aryl group and metal surfaces. , 2006, Journal of the American Chemical Society.

[82]  A. Turner,et al.  Polyetheretherketone as a biomaterial for spinal applications. , 2006, Biomaterials.

[83]  H. Kleinman,et al.  Matrigel: basement membrane matrix with biological activity. , 2005, Seminars in cancer biology.

[84]  W. Linhart,et al.  Response of primary fibroblasts and osteoblasts to plasma treated polyetheretherketone (PEEK) surfaces , 2005, Journal of materials science. Materials in medicine.

[85]  J. Pinson,et al.  Attachment of organic layers to conductive or semiconductive surfaces by reduction of diazonium salts. , 2005, Chemical Society reviews.

[86]  N. Lang,et al.  The Junctional Epithelium: from Health to Disease , 2005, Journal of dental research.

[87]  K. Neoh,et al.  Immobilization of galactose ligands on acrylic acid graft-copolymerized poly(ethylene terephthalate) film and its application to hepatocyte culture. , 2003, Biomacromolecules.

[88]  Kenneth M. Yamada,et al.  Fibronectin at a glance , 2002, Journal of Cell Science.

[89]  M. Yoshinari,et al.  Difference in penetration of horseradish peroxidase tracer as a foreign substance into the peri-implant or junctional epithelium of rat gingivae. , 2002, Clinical oral implants research.

[90]  J. Tour,et al.  Highly Functionalized Carbon Nanotubes Using in Situ Generated Diazonium Compounds , 2001 .

[91]  R. Farndale,et al.  The Collagen-binding A-domains of Integrins α1β1 and α2β1Recognize the Same Specific Amino Acid Sequence, GFOGER, in Native (Triple-helical) Collagens* , 2000, The Journal of Biological Chemistry.

[92]  A. Sonnenberg,et al.  Structure and function of hemidesmosomes: more than simple adhesion complexes. , 1999, The Journal of investigative dermatology.

[93]  V. Quaranta,et al.  Coating of titanium alloy with soluble laminin-5 promotes cell attachment and hemidesmosome assembly in gingival epithelial cells: potential application to dental implants. , 1997, Journal of periodontal research.

[94]  J. Pinson,et al.  Covalent Modification of Carbon Surfaces by Aryl Radicals Generated from the Electrochemical Reduction of Diazonium Salts , 1997 .

[95]  M. Yamato,et al.  Identification of integrins involved in cell adhesion to native and denatured type I collagens and the phenotypic transition of rabbit arterial smooth muscle cells. , 1995, Experimental cell research.

[96]  A. F. Recum,et al.  Applications and failure modes of percutaneous devices: A review , 1984 .

[97]  K Affeld,et al.  Design criteria for percutaneous devices. , 1984, Journal of biomedical materials research.