Immobilization of oligonucleotides on titanium based materials by partial incorporation in anodic oxide layers

Beutner, René; Michael, Jan; Förster, Anne; Schwenzer, Bernd; Scharnweber, Dieter

doi:10.1016/j.biomaterials.2009.01.047

Cited by 31 publications

(38 citation statements)

References 35 publications

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“…The 31-mer Oligonucleotides (GS-ODN) to anchor strands were synthesised by Biomers (Ulm, Germany). For complementary immobilisation of anchor strands (AS) an electrochemical setup was used, which has already been described by Beutner et al (2009). Briefl y, the samples were mounted to the bottom of a conical cell made from polyetherimide.…”

Section: Specimen Fabricationmentioning

confidence: 99%

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF – an in vitro study

Schliephake¹,

Strecker²,

Förster³

et al. 2012

eCM

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The aim of the present study was to test the hypothesis that sandblasted and acid etched titanium surfaces can be functionalised with vascular endothelial growth factor (VEGF) using oligonucleotides for anchorage and slow release. rhVEGF165 molecules were conjugated to strands of 30-mer non-coding DNA oligonucleotides (ODN) and hybridised to complementary ODN anchor strands which had been immobilised to the surface of sandblasted/acid etched (SAE) Ti specimens. Specimens with non-conjugated VEGF adsorbed to ODN anchor strands and to blank SAE surfaces served as controls. Specifi c binding of conjugated VEGF exhibited the highest percentage of immobilised VEGF (71.0 %), whereas non-conjugated VEGF only achieved 53.2 and 30.7 %, respectively. Cumulative release reached 54.0 % of the immobilised growth factor in the group of specifi cally bound VEGF after 4 weeks, whereas non-conjugated VEGF adsorbed to ODN strands released 78.9 % and VEGF adsorbed to SAE Ti surfaces released 97.4 %. Proliferation of human umbilical vein endothelial cells (HUVECs) was signifi cantly increased on the surfaces with specifi cally bound VEGF compared to the control surfaces and SAE Ti surfaces without VEGF. Moreover, the released conjugated VEGF exhibited biological activity by induction of von Willebrand Factor (vWF) in mesenchymal stem cells. It is concluded that the angiogenic functionalisation of SAE titanium surfaces can be achieved by conjugation of VEGF to ODN strands and hybridisation to complementary ODN strands that are anchored to the titanium surface. The angiogenic effect is exerted both through the immobilised and the released portion of the growth factor.

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Section: Specimen Fabricationmentioning

confidence: 99%

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF – an in vitro study

Schliephake¹,

Strecker²,

Förster³

et al. 2012

eCM

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“…In this context the method of binding and/or release of such factors is a crucial issue [13]. Promising results have been published by Michael et al who achieved immobilization of bioactive molecules on the implant surface in a two-step procedure: First, short strands of nucleic acids – “anchor strands” – were entrapped into a titanium oxide layer on the implant surface [14], [15]. Then, conjugates of bioactive molecules and complementary strands were hybridized to the surface modified with anchor strands [14], [16].…”

Section: Introductionmentioning

confidence: 99%

Improved Anchorage of Ti6Al4V Orthopaedic Bone Implants through Oligonucleotide Mediated Immobilization of BMP-2 in Osteoporotic Rats

et al. 2014

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The aim of the present study was to test the biocompatibility and functionality of orthopaedic bone implants with immobilized oligonucleotides serving as anchor stands for rhBMP-2 and rhVEGF-A conjugated with complementary oligonucleotides in an osteoporotic rat model. Al2O3-blasted acid etched Ti6Al4V implants, carrying oligonucleotide anchor strands and hybridized with rhBMP-2 or rhVEGF-A through complementary 31-mer oligonucleotide stands were inserted into the proximal tibia of ovariectomized rats. At the time of surgery (15 weeks after ovariectomy) microCT analysis showed significantly lower bone mineral density compared to non-ovariectomized animals. Bone-implant contact (BIC) and pullout-force were not negatively affected by non-hybridized anchor strands. Twelve weeks after surgery, a significantly higher pullout force was found for BMP-2 hybridized to the anchor strands compared to non-hybridized anchor strands or native samples, and on histomorphometric analysis BIC was highest in the BMP group. Thus, we could show the biocompatibility and in vivo functionality of this modular, self-organizing system for immobilization and subsequent release of BMP-2 in vivo.

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“…Common attempts to improve osseointegration and cellular signaling through growth factor delivery involve chemical conjugation with heparin or modification with titanium-binding motifs [97–99]. Surface modification techniques such as plasma spraying, acid-etching, anodic polarization and grit-blasting enhances growth factor binding by changing the surface chemical composition and topology [100–103]. Another surface modification technique is to apply coatings of bioactive polymers and hydrogels that physically entrap molecules against the material surface or within the porous structure to direct osteoinductive cellular function [104–106].…”

Section: Protein Therapymentioning

confidence: 99%

Strategies for controlled delivery of growth factors and cells for bone regeneration

Kasper

Mikos

2012

Advanced Drug Delivery Reviews

578

460

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The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering.

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Immobilization of oligonucleotides on titanium based materials by partial incorporation in anodic oxide layers

Cited by 31 publications

References 35 publications

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF – an in vitro study

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF – an in vitro study

Improved Anchorage of Ti6Al4V Orthopaedic Bone Implants through Oligonucleotide Mediated Immobilization of BMP-2 in Osteoporotic Rats

Strategies for controlled delivery of growth factors and cells for bone regeneration

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