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Research progress in surface modification technology of tantalum and porous tantalum in tissue engineering and dentistry!


Tantalum metal (Ta) has excellent corrosion resistance, high melting point, high strength, and wear resistance. It is widely used in heat-resistant materials such as aircraft and rockets, as well as industrial fields that require high-strength components. In addition, metal tantalum has good physical and mechanical properties and good biocompatibility, becoming another new type of biomaterial after titanium metal. It is widely used in medical related fields such as oral implant implantation, treatment of femoral head necrosis, coronary artery stent implantation, artificial acetabular prosthesis implantation, surgical suture production, etc.


In recent years, with the deepening of research on metallic tantalum, it has been found that porous tantalum has a honeycomb like three-dimensional structure similar to human cancellous bone, with low elastic modulus and high friction characteristics. Therefore, porous tantalum is also known as "tantalum bone". This article will introduce the current research status at home and abroad in terms of the structural mechanical properties, biological characteristics, surface modification technology research progress, and applications in dentistry of tantalum and porous tantalum.


1. Structural Mechanics and Biological Characteristics of Porous Tantalum


The preparation process of porous tantalum is relatively complex. The main methods include: vapor deposition, organic foam impregnation, powder sintering and laser rapid prototyping. The pore diameter of the porous tantalum prepared by the above methods is 300-600um, which has a higher porosity (66.7% -80%) compared with other metal materials with porous structure. This feature can accelerate the growth of tissue into the pores, and improve the nutrient exchange inside the porous tantalum, Thus, it has a high potential for tissue introverted growth. In addition, porous tantalum has characteristics such as low elastic modulus, high surface friction coefficient, and excellent mechanical properties. Its elastic modulus is 1.22 GPa, which is between cancellous bone (0.1-0.5 GPa) and dense bone (12-18 GPa). Implanting it into human bone tissue during medical treatment can avoid the "stress shielding" effect, which is conducive to the normal transmission of biological stress. A higher surface friction coefficient can increase the attachment surface of bone cells, which is conducive to the tight fitting and growth of cells, and has the function of guiding the differentiation and maturation of osteoblasts and exerting their osteogenic functions.


2. Research on surface modification of medical tantalum and porous tantalum in tissue engineering


Medical tantalum and porous tantalum have broad prospects in the fields of bone substitutes and dental implants due to their excellent tissue engineering properties and biocompatibility. Among them, the surface microenvironment of the implant is crucial. Good surface performance increases the contact area between the implant and bone tissue, improves the contact quality, and is conducive to the early stability of the implant, especially in the field of oral implantation. The concept of immediate implantation, immediate repair, and immediate weight bearing requires the implant to have good initial stability for early functional loading. Therefore, the current focus is on researching surface modification technologies of medical tantalum and porous tantalum to accelerate bone healing in implants and provide more durable and stable bone bonding. Since the 1970s, research has been focused on surface modification of tantalum metal and porous tantalum to achieve better biological properties. Looking back at the literature published domestically and internationally in the past decade, the main research on surface modification techniques includes: surface anodizing, biomimetic coatings, surface functionalization, alkali heat treatment activation modification, etc.


2.1 Surface anodizing


The function of surface anodizing technology is to rely on acidic solutions (sulfuric acid, oxalic acid, phosphoric acid, silicic acid, etc.) as electrolytes, and electrolyze them under a certain current and voltage to form an ordered nanotube film structure on the surface of Ta2O5 oxide layer, changing its biological characteristics. There have been studies on the biological properties of tantalum and porous tantalum surfaces after anodizing. Wang Na et al.'s in vitro experimental study reported that the modified tantalum pentoxide nanotube oxide layer structure on the surface of metal tantalum can enhance the adsorption of bovine serum albumin and fibronectin, enhance the adhesion and proliferation of rabbit bone marrow mesenchymal stem cells, and promote the expression of osteogenic factor alkaline phosphatase (ALP), type I collagen (CollagenI), and osteocalcin, promoting their osteogenic differentiation. Other scholars have found in vitro experiments that the surface of tantalum metal modified by tantalum pentoxide oxide layer can significantly promote the adhesion and proliferation of human osteoblasts, increase the expression of alkaline phosphatase in human osteoblasts, generate bone nodules, and mineralization and deposition of bone matrix.


2.2 Surface Biomimetic Coating Surface Treatment Technology


Based on the principle of heterogeneous nucleation, the implant is immersed in a supersaturated calcium phosphate solution, and calcium phosphate nucleates on its surface to form a coating. Due to the fact that biomimetic coatings are prepared under physiological conditions in aqueous solutions, their composition and structure are closer to the minerals in natural hard tissues. Elena et al. found that metal tantalum plates treated with calcium phosphate biomimetic coatings can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. F. Barrere's research team implanted cylindrical porous tantalum implants with calcium phosphate biomimetic coatings into goat back muscles. After 12 weeks, ectopic osteogenesis appeared in the implanted muscles; Subsequently, the research team implanted a porous tantalum implant with a calcium phosphate biomimetic coating into the femoral shaft of 14 week old female goats. The contact area between the implant and bone tissue was measured to be greater than that of the uncoated implant at weeks 6, 12, and 24 after surgery.


Scholars have also modified tantalum metal and porous scaffolds with calcium phosphate biomimetic coatings for in vivo and in vitro experiments. Compared with untreated smooth surfaces, the surface biomineralization performance of the calcium phosphate biomimetic coating modification treatment is significantly improved, while the hydrophilicity is also greatly improved, which is conducive to the attachment and extension of human osteoblasts and promotes the formation of guided bone regeneration in the repair of subchondral bone defects in rabbits.


2.3 Surface functionalization


Surface functionalization technology refers to the ability of the surface to combine with drugs in various ways to form self-assembled membranes, which have the ability to continuously release bioactive substances after implantation in the body. Previous studies have reported the use of electrostatic self-assembly on the surface of porous tantalum implants to embed the anticancer drug doxorubicin into a copolymer membrane composed of hyaluronic acid polyelectrolyte, methylated collagen, and ternary copolymer. After a month of in vivo experimental observation, it was found that doxorubicin was continuously released around the implant for one month and could inhibit the proliferation of chondrosarcoma cell line SW1353. Other scholars have studied the use of electro polishing technology and silane chemistry to combine RGD peptides (cRGDfK) onto the surface of tantalum metal to form functional surface modification. Experiments have shown that this treated surface can provide a good growth environment for cells. Vascular endothelial cells form higher cell density, better cell extension, and intercellular contact on the tantalum surface after binding to cRGDfK, compared to the non functional (non RGD peptide binding) surface, Improved the adhesion performance of Saos-2 cells on the treated surface, resulting in an increase in the number and area of Saos-2 cell adhesion.


KishoreUdipi et al. studied the covalent binding of low molecular weight superoxide dismutase mimetics (SODm) with anti-inflammatory properties onto the surface of tantalum plates and implanted them into the subcutaneous tissue of the back of female rats. Histological examination showed that the acute exudate of neutrophils in the acute phase (day 3) was significantly reduced compared to the control group, while the chronic phase of inflammation (day 28) was observed, The formation of foreign body multinucleated giant cells and fibrous cysts was also significantly reduced.


2.4 Alkali/Alkali Heat Treatment Activation Modification


Alkali heat treatment refers to soaking the implant in NaOH solution and then heat treating it at high temperature. After alkali heat treatment, the implant can form biomimetic apatite on the surface in the body and directly combine with bone through this. The sodium salt gel produced by pure NaOH treatment is unstable, and the combination with the metal matrix is weak, which will affect the combination between apatite and the metal matrix, and ultimately affect the combination between implant and bone. The heat treatment makes the sodium salt gel dehydrate into a dense and stable amorphous structure, and the combination between the apatite layer and the metal matrix is relatively tight.


Research has confirmed that alkaline heat treatment on the surface of porous tantalum alloy (Ti6Ta4Sn) scaffolds enhances the adsorption of simulated body fluid (SBF) and promotes the adhesion of Saos-2 cells. Other experimental studies have shown that porous tantalum undergoes alkaline treatment on its surface, and 3T3-E1 cells are inoculated on it. After five days of cultivation, actin fibers and bone like tissue are detected throughout 3T3-E1 cells. Animal experiments have shown that new bone appears between the implant and host bone at week 4; At weeks 4 and 12, new capillaries and bones grow into the pores of porous tantalum.


3. Application of Medical Tantalum and Porous Tantalum in Stomatology


Tantalum metal has been used as an implant material in the restoration and treatment of missing teeth patients. With the development of technology, porous tantalum has also been attempted to be applied in the field of implants. Due to its outstanding mechanical and biological properties, elastic modulus comparable to bone tissue, high friction coefficient, and ability to provide good bone bonding and initial stability for implants, it is called a trabecular implant. In addition, Its elastic modulus, which is equivalent to that of bone tissue (between cancellous and dense bone), allows the implant to disperse occlusal force into the surrounding bone during long-term oral functional loading, avoiding stress concentration.


Experiments have shown that during the process of occlusal force loading, traditional implants can absorb 30% of the load energy, while porous tantalum implants can absorb 50% -75%. The high friction coefficient makes it have good initial stability during the implant implantation process, thereby improving the bonding rate of implanted teeth, especially for implant patients with poor bone quality. At the same time, Professor Liu Hongchen proposed the concept of drug delivery for artificial dental implants. By loading drugs into porous tantalum artificial teeth, it is expected to improve the bone healing ability of damaged bone in bone metabolism diseases while promoting implant bone bonding. In addition, research on the role of porous tantalum in the repair of jaw bone defects is also underway. The three-dimensional structure of porous tantalum has pores, which are conducive to the adhesion of bone marrow mesenchymal stem cells and osteoblasts on its surface. The pore structure is similar to bone tissue, providing a good scaffold for the growth of bone tissue.


Related research reports have confirmed that porous tantalum particles have good osteogenic ability, and their repair effect for jaw bone defects is better than the commonly used Bio oss bone powder in clinical practice. An experimental model of jaw bone defects was constructed, and porous tantalum particles and Bio oss bone powder were implanted into the right and left jaw bone defect areas of beagles, respectively. Three months later, gross specimens, X-ray films, and hard tissue sections showed that the porous tantalum particle group had a significant increase in bone formation The maturity of bone tissue was higher than that of the control group (Bio oss bone powder group).


4. Summary


Due to their excellent biocompatibility, tantalum and porous tantalum have important clinical value and application prospects in various fields of medicine, such as dentistry, orthopedics, cardiovascular surgery, biomedical engineering, etc. The application of surface modification technology will enable metal tantalum and porous tantalum to have more excellent biological properties, greatly improving the binding ability of tantalum and porous tantalum implants to the surrounding bone interface, In order to better improve the clinical efficacy of implants.




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