Web of knowledge for

DONTAS

Contract number 171

National Authority: UEFISCDI

UNIVERSITATEA BABES BOLYAI

FACULTATEA DE CHIMIE SI INGINERIE CHIMICA

 

Development of new tools and smart Composites based on advanced nanotehnology FOR medical applications           

 

 

 

 

 

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OBJECTIVES

EXPECTED RESULTS

OBTAINED RESULTS

DISSEMINATION

 

 

 

 

 

 

·   Obtained results:

 

Phase 1:

 

Design, realization and characterization of some nanomaterials, powders and some composites, made of nanoHAPs and biopolymers (collagen type I: COL, and/or chitosan: CHI). Design, realization, and characterization of some surgical implants made from stainless steel.

 

The synthesis of some nanomaterials made from nanoHAPs modified with various Si concentrations, incorporated into polymers, namely collagen type 1 and/or chitosan. Chemical, structural and morphological characterization of obtained biomaterials.

 

Design and realization of four prototypes of stainless steel nails and plates with screws with applications in orthopedic surgery.

 

Development of several surgical techniques and methods for the insertion of stainless steel nails and plates with screws in bone tissue (in vitro) with applications in osteosynthesis with intramedullary implants.

 

Development of some innovative methods minimally invasive for osteosynthesis with plates and screws with applications in surgical treatment of osteoporotic bone fractures.

 

Dissemination: ♦Five original scientific research articles were published; ♦3 ISI articles; ♦2 articles published in Journals recognized by CNCSIS; ♦Nine original scientific research papers communicated at 6 (3 international and 3 national) scientific events in the field of the project.
 

Phase 2:

 

Various DONTAS nanomaterials have been synthesized: pure hydroxyapatite, mono-substituted and multi-substituted HAP with different cations and anions by precipitation from aqueous phase. The precipitate was freeze dried and then calcined at a temperature of 650 °C for 6 h. These scientific and technological activities represent a pioneering work in the field of bio-ceramics and nano phosphates. Samples obtained have been investigated by X-ray diffraction (XRD) and SEM imaging, and chemically characterized by SEM-EDX. From the analysis of the XRD patterns the phases existent in the synthesized nano materials were identified, and their proportion was estimated in the different synthesized samples.

 

New nanomaterials have been designed and prepared, made of nanoHAPs where the nanoparticles were coated with polymers layers, namely with type I collagen, COL, obtaining nanoHAP/COL, with chitosan: CHI, resulting nanoHAP/CHI and with chitosan and collagen, resulting in nanoHAP/CHI/COL. The DONTAS composite nano materials were used in osteoblasts cell cultures and showed an enhanced biocompatibility compared to those made from the corresponding nanopowders only.

 

Osteo-articular traumatology represents an important issue in the clinical and research activity of the DONTAS team and in the world. Using innovative nano-technologies developed in DONTAS project has resulted in more efficient treatment of patients and in improved results in the treatment of bone fractures. Metal implants coated with DONTAS nano materials are used, promoting the healing and recovery, and avoiding possible complications. Efforts of the DONTAS team were directed towards application of different osteosynthesis procedures which produce a minimum surgical trauma, realizing a stable mounting and finally to ensuring the healing of patients without major complications, facilitating functional recovery therapy in order to return more rapidly to the preoperative status.

 

The efforts of the SME which is co-financing the project are directed in line with the current trends in the field of orthopedic research. DONTAS activity has focused on the development of different implants - rods, screws and plates, prostheses made of titanium - in combination with biological factors added in order to improve bone fixation. Based on the research executed, design principles were established, and the material was selected, on which destructive and non-destructive examinations were realized. The 3D modeling was realized for determination of experimental models, execution documentation has been developed and prototypes have been performed for the surgical kit made up of titanium plates and rods, of various shapes and sizes, adaptable to different complex surgical situations and orthopedic treatment.

 

The obtained results were disseminated through: ♦publication of 8 original scientific articles; ♦6 ISI articles, ♦publication of 2 articles in journals recognized by CNCSIS; ♦published a patent; ♦published a reference book in orthopedics and ♦participation with 18 original works in 6 scientific events in the project profile: ♦4 international conferences, congresses or workshops, with 15 works, and ♦2 national conferences with 3 works.
 

Phase 3:

 

All objectives and all research activities were fully accomplished in total agreement with the DONTAS project. Series of several tens of syntheses were designed and realized to control the shape, size, crystallinity and porosity of nanoparticles within various nanomaterials based on nano phosphates enriched in different ions, to control the wanted compositions, to better mimic the requirements for natural bone regeneration by using advanced nano technologies. The obtained nanomaterials were physically and chemically characterized by proper methods and specific techniques: XRD, FTIR, Raman, BET, SEM, TEM and AFM. Hundreds of scaffolds were fabricated from DONTAS nanomaterials by using the thin film technique, layer by layer self-assemblies. They were structurally and morphologically characterized and biologically evaluated in various cell cultures. The scaffolds, made of synthetic DONTAS nanomaterials, are biocompatible and demonstrated an enhanced osteoblasts activity, by using immune staining techniques with antibodies and fluorescence microscopy. The biological advantages of porous DONTAS nano phosphates make the DONTAS nanomaterials potential candidates for bone tissue engineering and bone reconstruction and regeneration.

 

Furthermore, the Langmuir-Blodgett self-assembly technique was used for the mineralization of polymer fibers with inorganic nanoparticles at the air/water interface as well as for the fabrication of fibrous scaffolds at lateral surface pressures characteristic for the systems in vivo. The structural characteristics of polymer fibers and their mechanical properties, in the absence and the presence of various DONTAS inorganic nanoparticles, mainly elasticity Young moduli, were determined by AFM and AFM spectroscopy, primarily by force curves in contact mode. This scientific and technical approach is a premier leading to scaffolds of various porosities to better satisfy the necessity of cell adhesion and proliferation. The scaffolds were characterized by XRD, FTIR, Raman, BET, SEM, TEM and AFM and AFM spectroscopy (e.g. force curves).

 

The treatment of bone fractures and of osteo-articular traumatology represents a major part of the clinical and research activity of the DONTAS surgeons’ team. Using innovative nano-technologies in DONTAS project has resulted in more efficient treatment of patients and the results of surgery in bone fractures are improved. Metal implants coated with DONTAS nano materials were described by the finite element theory. They were used to promote the healing and recovery, avoiding possible complications. Efforts of the DONTAS team are continuously directed towards an improved osteointegration of implants and prostheses to produce a minimum surgical trauma, ensuring the healing of patients without major complications. Several improved methods and techniques were fully developed, like the retrograde intramedullary osteosynthesis in distal femur fractures and the intramedullary osteosynthesis in proximal femur fractures as well as osteosynthesis with plates, nails and screws from titan or stainless steel in diaphyseal tibial fractures and an innovative minim invasive “all-inside” anterior cruciate ligament in knee reconstruction.

 

The efforts of the SME which is co-financing the project are directed to the field of orthopedic research, namely to surgical metallic implants. The SME activity has focused on the development of different DONTAS implants, like rods, screws and plates as well as prostheses, made of titanium, stainless steel or stainless steel coated with cobalt-chrome or tantalum, improved for bone surgery, in combination with biological factors added in order to improve bone fixation. The SME developed methods and techniques to fabricate the implants and to fully characterize their surface, using metallographic images, SEM images and roughness measurements.

 

The obtained results of scientific research, development and innovation were disseminated through: publications of ♦11 original scientific research articles; ♦seven ISI articles; ♦3 articles published in BDI journals; ♦one paper published in Proceedings IEEE; ♦published a specialty book of orthopedic surgery; participation with ♦14 original research works in 5 scientific events in the project research field, international conferences, congresses or workshops as well as national conferences.
 

Phase 4:

 

All objectives and all research activities were fully realized as primarily established in the DONTAS project. Series of many syntheses were designed and realized to control the shape, size and crystallinity of nanoparticles and porosity of various powders based on nano hydroxyl phosphates enriched in different ions, to better monitor the chemical compositions of nanomaterials and consequently better mimic the requirements for bone fixation, repair and regeneration by using advanced nano technologies. The obtained DONTAS nano powders were physically and chemically characterized by proper methods and specific techniques: XRD, FTIR, Raman, BET, SEM, TEM and AFM.

 

The chemical stability of DONTAS nanomaterials in various aqueous media, including simulated body fluid was evaluated and the release of ions was determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). ICP-AES results showed a relatively slow dissolution of DONTAS nano powders. The release of ions from DONTAS materials is continuously slowly increasing in time after their immersion in various media.

 

Further, the synthesis of DONTAS nanoparticles in the presence of natural polymers was developed for the preparation of innovative self-assembled DONTAS nanocomposites used for the fabrication of different scaffolds and coatings on metallic implants. Furthermore, new DONTAS biomaterials based on synthetic polymers and silicates were developed and fully structurally and morphologically characterized. Their mechanical properties were determined particularly by using compression tests, and they are in the appropriate range to natural bone.

 

The bioactivity of DONTAS nanocomposites was evaluated in simulated body fluid and the production of biological nanomaterials on DONTAS scaffolds was investigated. This scientific and technical approach is a premier leading to scaffolds of various porosities to better satisfy the necessity for cell adhesion, growth and proliferation as well as for the production of bone de novo. The scaffolds were characterized by XRD, FTIR, Raman, BET, SEM, TEM and AFM spectroscopy (e.g. force curves).

 

The treatment of osteo-articular trauma and degenerative conditions represents a major part of the clinical and research activity in the world and within the DONTAS project. The use of DONTAS materials and innovative nano-technologies developed in DONTAS project has resulted in a more efficient treatment of patients in bone fixation, repair and regeneration. Metallic implants coated with DONTAS nanocomposites were used to promote the healing and recovery, avoiding possible complications. Moreover, the efforts of the DONTAS team are constantly directed towards an improved osteointegration of implants and prostheses to produce a minimum surgical trauma, ensuring the healing of patients without major complications. Several improved methods and techniques were fully developed, like the enhanced osteosynthesis in femur fractures and in shoulder fractures as well as osteosynthesis with plates and screws from tantalum, titan or stainless steel in tibial fractures and an innovative minim invasive surgical approach in knee reconstruction.

 

The efforts of the SME which is co-financing the project are constantly directed to the field of orthopedic metallic implants. The SME activity has focused on the development of different DONTAS implants, like rods, screws and plates as well as prostheses, made of tantalum, titanium, stainless steel or stainless steel coated with cobalt, chrome or tantalum, improved for bone surgery, in combination with biological factors and DONTAS composites added in order to improve bone fixation. The SME developed innovative methods and improved techniques to fabricate the metallic implants. Furthermore, SME partners developed original techniques to determine with precision the thickness of the cobalt and the chrome layers deposited on the stainless steel implants. They fully characterized their surface, using metallographic images, SEM and AFM images as well as roughness measurements.

 

The obtained results of scientific research, development and innovation, were disseminated through: ♦publications of 11 original scientific research articles; ♦ six ISI articles; ♦4 articles published in BDI journals; ♦one specialty book of orthopedics; ♦participation with 9 original research works in 6 scientific events within the project research field, international conferences, congresses or workshops as well as national conferences; ♦two workshops with international participation; ♦6 Ph.D. Thesis in the field of DONTAS project.

 

Phase 5:
 

Project objectives: the project DONTAS is particularly complex and is aligned with up to date research worldwide regarding the development of new metallic implants coated with smart composites based on advanced nanotechnology, with multiple medical applications. To this aim nano powders and smart nanostructured DONTAS composites, based on phosphates and silicates as well as on natural and synthetic polymers, have been designed, developed and characterized in terms of chemical, structural, morphological, mechanical, biological and biomedical properties. Metal Implants were made form tantalum, titanium, stainless steel, or silver and covered with DONTAS composites. Surgical techniques and methods were developed for the implantation of rods and plates made of metal and/or metal coated with nanostructured biomaterials or smart composites in bone tissue (in vitro).
5th stage objectives: ♦ series of syntheses have been designed and realized in order to control the shape, size and crystallinity of DONTAS nanoparticles, using co-precipitation technique, sol-gel method, as well as advanced thermal processing ♦ the nanoparticles made of nano phosphates (nanoP) substituted with essential elements, or nano forsterite (nanoF) were characterized: chemically - by elemental analysis (ICP-AES), structurally and morphologically ♦series of scaffolds consisting of DONTAS nanopowders and DONTAS nanocomposites, made of nanoP:collagen, nanoP:chitosan, PMMA-nanoP, or PLA-nanoP were prepared using the DONTAS nanotechnology or thin films - self-assembly – layer by layer, and characterized by XRD, FTIR, FT-Raman, TEM, AFM and SEM ♦ the scaffolds and DONTAS nano materials were characterized by XRD, FTIR, Raman, BET, SEM, TEM, and AFM ♦ the mechanical properties of the DONTAS nanocomposites were determined ♦ the biocompatibility of obtained DONTAS biomaterials was assessed (e.g.. cells viability using Alamar blue: MTT and fluorescein diacetate: FDA assays) in cell cultures of human osteoblasts (bone forming cells) or fibroblasts ♦the bioactivity of scaffolds was assessed in various biological fluids, e.g. simulated body fluid: SBF and in osteogenic culture medium (osteogenic DMEM) ♦ the biological nanoP, formed on the surface of scaffolds made of the orthopedic nanobiostructures developed in this stage, was determined ♦ surgical techniques and methods have been developed for the implantation of rods and plates made of metal: tantalum or silver, coated with DONTAS composites, in bone tissue (in vitro) ♦ surgical implants (rods and plates), made of tantalum or silver, coated with nanostructured DONTAS materials, were designed and realized.