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Covalent Attachment of P15 Peptide to Ti Alloy Surface Modified with Polymer to Enhance Osseointegration of Implants.

ABSTRACT: Titanium (Ti) and its alloys are used in orthopedic and dental implants due to their excellent physical properties and biocompatibility. Although Ti exhibits superior osteoconductive properties compared to those of polymer-based implants, improved bone-on growth properties are required for enhanced surgical outcomes and improved recovery surgical interventions. Herein, we demonstrate a novel surface modification strategy to enhance the osteoconductivity of Ti surfaces through the grafting-from procedure of a reactive copolymer via surface-initiated atom transfer radical polymerization (SI-ATRP). Then, postpolymerization conjugation of the P15 peptide, an osteoblast binding motif, was successfully carried out. Subsequent in vitro studies revealed that the surface modification promoted osteoblast attachment on the Ti discs at 6 and 24 h. Moreover, mineral matrix deposition by osteoblasts was greater for the surface-modified Ti than for plain Ti and P15 randomly absorbed onto the Ti surface. These results suggest that the strategy for postpolymerization incorporation of P15 onto a Ti surface with a polymer interface may provide improved osseointegration outcomes, leading to enhanced quality of life for patients.

SUBMITTER: Fu L

PROVIDER: S-EPMC6993989 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Covalent Attachment of P15 Peptide to Ti Alloy Surface Modified with Polymer to Enhance Osseointegration of Implants.

Fu Liye L Omi Maiko M Sun Mingkang M Cheng Boyle B Mao Gordon G Liu Tong T Mendonça Gustavo G Averick Saadyah E SE Mishina Yuji Y Matyjaszewski Krzysztof K

ACS applied materials & interfaces 20191010 42

Titanium (Ti) and its alloys are used in orthopedic and dental implants due to their excellent physical properties and biocompatibility. Although Ti exhibits superior osteoconductive properties compared to those of polymer-based implants, improved bone-on growth properties are required for enhanced surgical outcomes and improved recovery surgical interventions. Herein, we demonstrate a novel surface modification strategy to enhance the osteoconductivity of Ti surfaces through the grafting-from p ...[more]

PMID: 31599570

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Project description:Ti is characteristically bioinert and is supplemented with modifications in surface topography and chemistry to find use in biomedical applications. The aim of this study is to understand the effects of surface charge on TiO2 nanotubes (TNT) on Ti implants towards early stage osseointegration. We hypothesize that charge storage on TNT will improve bioactivity and enhance early-stage osseointegration in vivo. Commercially pure Ti surface was altered by growing TNT via anodic oxidation followed by the introduction of surface charge through electrothermal polarization to form bioelectret. Our results indicate a stored charge of 37.15 ± 14 mC/cm2 for TNT surfaces. The polarized TNT (TNT-Ps) samples did not show any charge leakage up to 18 months, and improved wettability with a measured contact angle less than 1°. No cellular toxicity through osteoblast proliferation and differentiation in vitro were shown by the TNT-Ps. Enhanced new bone formation at 5 weeks post-implantation for the TNT-Ps in contrast to TNTs was observed in vivo. Histomorphometric analyses show ∼40% increase in mineralized bone formation around the TNT-P implants than the TNTs at 5 weeks, which is indicative of accelerated bone remodeling cycle. These results show that stored surface charge on TiO2 nanotubes helped to accelerate bone healing due to early-stage osseointegration in vivo. STATEMENT OF SIGNIFICANCE: To improve surface bioactivity of metallic biomaterials, various approaches have been proposed and implemented. Among them, stored surface charge has been explored to enhance biological responses for hydroxyapatite ceramics where charged surfaces show favorable bone tissue ingrowth. However, surface charge effects have not yet been explored as a way to mitigate bio-inertness of titanium. This study intends to understand novel integration of bioactive titania-nanotubes and charge storage as surface modification for titanium implants. Our results show excellent biological response due to surface charge on titania-nanotubes offering possibilities of faster healing particularly for patients with compromised bone health.

Project description:Currently, selective laser melting (SLM) has been thriving in implant dentistry for on-demand fabricating dental implants. Based on the coarse microtopography of SLM titanium surfaces, constructing nanostructure to form the hierarchical micro-nano topography is effective in enhancing osseointegration. Given that current nanomodification techniques of SLM implants, such as anodization and hydrothermal treatment, are facing the inadequacy in costly specific apparatus and reagents, there has been no recognized nanomodified SLM dental implants. The present study aimed to construct hierarchical micro-nano topography on self-made SLM dental implants by a simple and safe inorganic chemical oxidation, and to evaluate its contribution on osteoblastic cells bioactivity and osseointegration. The surface chemical and physical parameters were characterized by FE-SEM, EDS, profilometer, AFM, and contact angle meter. The alteration on bioactivity of MG-63 human osteoblastic cells were detected by qRT-PCR. Then the osseointegration was assessed by implanting implants on the femur condyle of New Zealand Rabbits. The hierarchical micro-nano topography was constituted by the microrough surface of SLM implants and nanoneedles (diameter: 20∼50 nm, height: 150∼250 nm), after nanomodifying SLM implants in 30% hydrogen peroxide and 30% hydrochloride acid (volume ratio 1:2.5) at room temperature for 36 h. Low chemical impurities content and high hydrophilicity were observed in the nanomodified group. Cell experiments on the nanomodified group showed higher expression of mitophagy related gene (PINK1, PARKIN, LC3B, and LAMP1) at 5 days and higher expression of osteogenesis related gene (Runx2 and OCN) at 14 days. In the early stage of bone formation, the nanomodified SLM implants demonstrated higher bone-to-implant contact. Intriguingly, the initial bone-to-implant contact of nanomodified SLM implants consisted of more mineralized bone with less immature osteoid. After the cessation of bone formation, the bone-to-implant contact of nanomodified SLM implants was equal to untreated SLM implants and marketable TixOs implants. The overall findings indicated that the inorganic chemical oxidized hierarchical micro-nano topography could enhance the bioactivity of osteoblastic cells, and consequently promote the peri-implant bone formation and mineralization of SLM dental implants. This study sheds some light on improvements in additive manufactured dental implants.

Project description:BackgroundTitanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications.MethodsWe introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student's t-test.ResultsMicroscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations.ConclusionWe believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.

Dataset Information

Covalent Attachment of P15 Peptide to Ti Alloy Surface Modified with Polymer to Enhance Osseointegration of Implants.

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Covalent Attachment of P15 Peptide to Ti Alloy Surface Modified with Polymer to Enhance Osseointegration of Implants.

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