RGD-modified dihydrolipoamide dehydrogenase as a molecular bridge for enhancing the adhesion of bone forming cells to titanium dioxide implant surfaces.

Titanium and its alloys are widely used in dental- and orthopedic implants, the outer surface of which is often oxidized to titanium dioxide (TiO2 ). To achieve efficient osseointegration with bone-forming cells, it is desirable to counter the formation of the soft fibrous tissue around the implant by creating strong and stable interactions between the implant surface and bone-forming osteoblasts. To address this challenge, a bioactive coating had to be designed. Protein adsorption to TiO2 is well known in the literature, but it is mostly characterized by weak associations, rendering less efficient implant osseointegration. We have previously demonstrated the unique conjugation between the dihydrolipoamide dehydrogenase (DLDH) protein and TiO2 surfaces, based on specific coordinative bonding via Cys-His-Glu-Asp motif residues. To enhance cell binding to DLDH and facilitate osseointegration, DLDH was bioengineered to include Arg-Gly-Asp (RGD) moieties (DLDHRGD ). Coating TiO2 disks with DLDHRGD led to improved adherence of integrin-expressing osteogenic MBA-15 to the surface of the disks. Following the enhanced adsorption, higher proliferation rates of the adherent cells, as well as faster mineralization were observed, compared to controls. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 545-551, 2019.

[1]  K. Sandhage,et al.  Surface modification of bulk titanium substrates for biomedical applications via low-temperature microwave hydrothermal oxidation. , 2018, Journal of biomedical materials research. Part A.

[2]  O. Ashur-Fabian,et al.  RGD-modified dihydrolipoamide dehydrogenase conjugated to titanium dioxide nanoparticles – switchable integrin-targeted photodynamic treatment of melanoma cells , 2018, RSC advances.

[3]  F. Luyten,et al.  Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo , 2018, Stem Cell Research & Therapy.

[4]  Y. Tsfadia,et al.  The involvement of coordinative interactions in the binding of dihydrolipoamide dehydrogenase to titanium dioxide—Localization of a putative binding site , 2017, Journal of molecular recognition : JMR.

[5]  Daniel Buser,et al.  Osseointegration of titanium, titanium alloy and zirconia dental implants: current knowledge and open questions , 2017, Periodontology 2000.

[6]  P. Tengvall,et al.  Foreign Body Reaction to Biomaterials: On Mechanisms for Buildup and Breakdown of Osseointegration. , 2016, Clinical implant dentistry and related research.

[7]  J. Montero,et al.  Comparison of clinical performance of zirconia implants and titanium implants in animal models: a systematic review. , 2014, The International journal of oral & maxillofacial implants.

[8]  D. Buser,et al.  Bone apposition to a titanium-zirconium alloy implant, as compared to two other titanium-containing implants. , 2012, European cells & materials.

[9]  M. Islam,et al.  Synergistic enhanced photocatalytic and photothermal activity of Au@TiO2 nanopellets against human epithelial carcinoma cells. , 2011, Physical chemistry chemical physics : PCCP.

[10]  R. Schmelzeisen,et al.  Bone engineering-vitalisation of alloplastic and allogenic bone grafts by human osteoblast-like cells. , 2010, The British journal of oral & maxillofacial surgery.

[11]  Yin-Sheng Ma,et al.  Interaction of nano-TiO2 with lysozyme: insights into the enzyme toxicity of nanosized particles , 2010, Environmental science and pollution research international.

[12]  Darren J. Martin,et al.  Differential plasma protein binding to metal oxide nanoparticles , 2009, Nanotechnology.

[13]  Noam Eliaz,et al.  The effect of surface treatment on the surface texture and contact angle of electrochemically deposited hydroxyapatite coating and on its interaction with bone-forming cells. , 2009, Acta biomaterialia.

[14]  Niklaus P Lang,et al.  Implant surfaces and design (Working Group 4). , 2009, Clinical oral implants research.

[15]  T. Walsh,et al.  Interplay of sequence, conformation, and binding at the Peptide-titania interface as mediated by water. , 2009, ACS applied materials & interfaces.

[16]  Sadanari Jindou,et al.  The titanium binding protein of Rhodococcus ruber GIN1 (NCIMB 40340) is a cell‐surface homolog of the cytosolic enzyme dihydrolipoamide dehydrogenase , 2009, Journal of molecular recognition : JMR.

[17]  K. Shiba,et al.  Directional BMP-2 for functionalization of titanium surfaces. , 2009, Biomaterials.

[18]  P. Trevilatto,et al.  Failing Factors Associated With Osseointegrated Dental Implant Loss , 2007, Implant dentistry.

[19]  V. Sobolev,et al.  Prediction of transition metal‐binding sites from apo protein structures , 2007, Proteins.

[20]  P. Layrolle,et al.  Surface treatments of titanium dental implants for rapid osseointegration. , 2007, Dental materials : official publication of the Academy of Dental Materials.

[21]  Yong Sun,et al.  Thick rutile layer on titanium for tribological applications , 2007 .

[22]  B. Saramago,et al.  Human serum albumin adsorption on TiO2 from single protein solutions and from plasma. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[23]  E. Kokkoli,et al.  Biomimetic peptide-amphiphiles for functional biomaterials: the role of GRGDSP and PHSRN. , 2004, Biomacromolecules.

[24]  R. Kenig,et al.  A TiO2‐Binding Protein isolated from Rhodococcus Strain GIN‐1 (NCIMB 40340) – Purification, Properties and Potential Applications , 2003 .

[25]  O. Cámara,et al.  Adsorption of human serum albumin (HSA) onto colloidal TiO2 particles, Part I. , 2003, Journal of colloid and interface science.

[26]  M. Niinomi,et al.  Effect of microstructure on fracture characteristics of Ti-6Al-2Sn-2Zr-2Mo-2Cr-Si , 2001 .

[27]  J. Gunsolley,et al.  A multi-center study comparing dual acid-etched and machined-surfaced implants in various bone qualities. , 2001, Journal of periodontology.

[28]  S. Ramakrishna,et al.  Biomedical applications of polymer-composite materials: a review , 2001 .

[29]  Hongbiao Dong,et al.  Enhanced wear resistance of titanium surfaces by a new thermal oxidation treatment , 2000 .

[30]  D. Benayahu,et al.  Dexamethasone regulation of marrow stromal‐derived osteoblastic cells , 1996, Journal of cellular biochemistry.

[31]  D. Hammer,et al.  Biological Adhesion at Interfaces , 1996 .

[32]  S. Wientroub,et al.  Bone marrow interface: Preferential attachment of an osteoblastic marrow stromal cell line , 1995, Journal of cellular biochemistry.

[33]  Buddy D. Ratner,et al.  Advances in the analysis of surfaces of biomedical interest , 1995 .

[34]  S. Wientroub,et al.  Mineralization of marrow-stromal osteoblasts MBA-15 on three-dimensional carriers , 1994, Calcified Tissue International.

[35]  S. Wientroub,et al.  Bone formation by marrow osteogenic cells (MBA‐15) is not accompanied by osteoclastogenesis and generation of hematopoietic supportive microenvironment , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[36]  S. Wientroub,et al.  Subpopulations of marrow stromal cells share a variety of osteoblastic markers , 1991, Calcified Tissue International.

[37]  S. Wientroub,et al.  Bone marrow‐derived stromal cell line expressing osteoblastic phenotype in vitro and osteogenic capacity in vivo , 1989, Journal of cellular physiology.

[38]  J. Aubin,et al.  Mineralized bone nodules formedin vitro from enzymatically released rat calvaria cell populations , 1986, Calcified Tissue International.

[39]  E. Ruoslahti,et al.  Serum spreading factor (vitronectin) is present at the cell surface and in tissues. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[40]  B. Kasemo.  Biocompatibility of titanium implants: surface science aspects. , 1983, The Journal of prosthetic dentistry.

[41]  F. Xiao,et al.  Apatite-forming ability of hydrothermally deposited rutile nano-structural arrays with exposed {101} facets on Ti foil , 2017, Journal of Materials Science.

[42]  S. Berner,et al.  Toward optimizing dental implant performance: Surface characterization of Ti and TiZr implant materials. , 2017, Dental materials : official publication of the Academy of Dental Materials.

[43]  J. Mao,et al.  A chimeric peptide that binds to titanium and mediates MC3T3-E1 cell adhesion , 2010, Biotechnology Letters.

[44]  U. Akavia,et al.  Differentiation of bone marrow stroma-derived mesenchymal cells. , 2007, Current medicinal chemistry.

[45]  D. Benayahu,et al.  Characterization of adhesion and differentiation markers of osteogenic marrow stromal cells , 2005, Journal of cellular physiology.

[46]  Ulrike Diebold,et al.  The surface science of titanium dioxide , 2003 .

[47]  D. Puleo,et al.  RGDS tetrapeptide binds to osteoblasts and inhibits fibronectin-mediated adhesion. , 1991, Bone.

[48]  L. Vroman.  The Importance of Surfaces in Contact Phase Reactions , 1987, Seminars in thrombosis and hemostasis.