Nobuyo Narita

Carbon Nanotubes with High Bone‐Tissue Compatibility and Bone‐Formation Acceleration Effects

Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

Safe clinical use of carbon nanotubes as innovative biomaterials.

Carbon nanotubes (CNTs) are structurally described as sheets of six-membered carbon atom rings (i.e., graphene) rolled up into cylinders. CNTs with only one layer are known as single-walled CNTs (SWCNTs), and those with two or more layers are known as multiwalled CNTs (MWCNTs). Cup-stacked carbon nanotubes and carbon nanohorns are also sometimes called CNTs.1−3 Currently, these very attractive carbon materials and nanomaterials are a subject of vigorous product development in a broad range of fields.4−11 The reasons are that CNTs have useful electrical, thermal, and mechanical characteristics, and their base material performance can be improved by combination with other materials.12−23 A recent industrial application of CNTs as an electrode additive to lithium-ion batteries is based on their excellent electrical characteristics. Addition of CNTs prevents battery deterioration and substantially lengthens time to recharging. It is doubtless that the demand for high-performance batteries will grow increasingly with multifunctionalization of personal computers and mobile phones, development of new mobile terminals, spread of electric vehicles, and other factors.24−30 Composite materials with the excellent mechanical characteristics of CNTs have already been used in sporting goods such as golf clubs, tennis rackets, and bicycles. CNTs are also expected to have applications that reduce the weight of aircraft and automobiles.10,14,31−35 A wide variety of advantages are gained from the use CNTs in precision parts as well. CNTs are also used in transistors and memory devices, and enhance their efficiency. The use of CNTs in various displays and TV screens continues to increase in rate. CNTs are also widely used in products designed to prevent static electricity, to shield electromagnetic waves, to store electricity, and for other purposes.36−45 Furthermore, Japan is now facing nuclear energy issues stemming from the accident at Tokyo Electric Power Company’s Fukushima No. 1 nuclear power plant. As a result, CNTs are expected to play a major role in developing new energy sources such as solar photovoltaic power generation and wind power generation.46−52 In the medical field, extensive research activities are underway to develop new CNTs biomaterials for use in the treatment and diagnosis of disease. For example, application of CNTs to cancer treatment and diagnosis, such as in drug delivery systems (DDSs) for treatment of cancer, hyperthermia, and in vivo imaging, has been investigated.53−57 In a study that aimed at applying CNTs to regenerative medicine, CNTs were found to work excellently as scaffold materials for nerve and bone tissue regeneration.58−63 Furthermore, R&D activities are underway to improve the mechanical strength and durability of implants by combining CNTs with existing biomaterials.64−67 Besides, numerous ideas have been put forth about how CNTs can be used in the treatment of a variety of diseases. Figure ​Figure11 shows the trend in the number of articles found in the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) (accessed 20 March 2014) by searches using “carbon nanotubes” and “biomaterials” as keywords. The number has been soaring since 2005, suggesting that CNTs research has become a highly competitive field worldwide over the past few years. Of course, numerous articles on the biological applications of CNTs do exist that cannot be captured with these two simple keywords, and the graphic representation of this trend is no more than an indicator of the increase in this research over time. Figure 1 Time trends for the number of articles found in the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) (accessed 20 March 2014) by search using “carbon nanotubes” and “biomaterials” as keywords. Recent years have seen ...

Carbon Nanotubes for Biomaterials in Contact with Bone

Carbon nanotubes (CNTs) possess exceptional mechanical, thermal, and electrical properties, facilitating their use as reinforcements or additives in various materials to improve the properties of the materials. Furthermore, chemically modified CNTs can introduce novel functionalities. In the medical field, biomaterials are expected to be developed using CNTs for clinical use. Biomaterials often are placed adjacent to bone. The use of CNTs is anticipated in these biomaterials applied to bone mainly to improve their overall mechanical properties, for applications such as high-strength arthroplasty prostheses or fixation plates and screws that will not fail. In addition, CNTs are expected to be used as local drug delivery systems (DDS) and/or scaffolds to promote and guide bone tissue regeneration. However, studies examining the use of CNTs as biomaterials still are in the preliminary stages. In particular, the influence of CNTs on osteoblastic cells or bone tissue is extremely important for the use of CNTs in biomaterials placed in contact with bone, and some studies have explored this. This review paper clarifies the current state of knowledge in the context of the relationship between CNTs and bone to determine whether CNTs might perform in biomaterials in contact with bone, or as a DDS and/or scaffolding for bone regeneration.

Multiwalled Carbon Nanotubes Specifically Inhibit Osteoclast Differentiation and Function

Since attention has been paid to the use of multiwalled carbon nanotubes (MWCNTs) as biomaterials in contact with bone, it is critical to understand the reaction of bone cells to MWCNTs. We show that MWCNTs inhibit osteoclastic bone resorption in vivo and that MWCNTs inhibit osteoclastic differentiation and suppressed a transcription factor essential for osteoclastogenesis in vitro. These results suggest that MWCNTs have beneficial effects on bones when they are used as biomaterials.

Analysis of pelvic movement in the elderly during walking using a posture monitoring system equipped with a triaxial accelerometer and a gyroscope

The incidence of falls in the elderly is increasing with the aging of society and is becoming a major public health issue. From the viewpoint of prevention of falls, it is important to evaluate the stability of the gait in the elderly people. The pelvic movement, which is a critical factor for walking stability, was analyzed using a posture monitoring system equipped with a triaxial accelerometer and a gyroscope. The subjects were 95 elderly people over 60 years of age. The criteria for instability were open-eye standing on one leg for 15s or less, and 11s or more on 3m timed up and go test. Forty subjects who did not meet both of these criteria comprised the stable group, and the remaining 55 subjects comprised the unstable group. Pelvic movement during walking was compared between the two groups. The angle, angular velocity, and acceleration were analyzed based on the wave shape derived from the device worn around the second sacral. The results indicated that pelvic movement was lower in all three directions in the unstable group compared to the stable group, and the changes in the pelvic movement during walking in unstable elderly people were also reduced. This report is the first to evaluate pelvic movement by both a triaxial accelerometer and a triaxial gyroscope simultaneously. The characteristics of pelvic movement during walking can be applied in screening to identify elderly people with instability, which is the main risk factor associated with falls.

Biocompatibility and bone tissue compatibility of alumina ceramics reinforced with carbon nanotubes

AIMS The addition of carbon nanotubes (CNTs) remarkably improves the mechanical characteristics of base materials. CNT/alumina ceramic composites are expected to be highly functional biomaterials useful in a variety of medical fields. Biocompatibility and bone tissue compatibility were studied for the application of CNT/alumina composites as biomaterials. METHODS & RESULTS Inflammation reactions in response to the composite were as mild as those of alumina ceramic alone in a subcutaneous implantation study. In bone implantation testing, the composite showed good bone tissue compatibility and connected directly to new bone. An in vitro cell attachment test was performed for osteoblasts, chondrocytes, fibroblasts and smooth muscle cells, and CNT/alumina composite showed cell attachment similar to that of alumina ceramic. DISCUSSION & CONCLUSION Owing to proven good biocompatibility and bone tissue compatibility, the application of CNT/alumina composites as biomaterials that contact bone, such as prostheses in arthroplasty and devices for bone repair, are expected.

Carbon Nanotubes Induce Bone Calcification by Bidirectional Interaction with Osteoblasts

Multi-walled carbon nanotubes (MWCNTs) promote calcification during hydroxyapatite (HA) formation by osteoblasts. Primary cultured osteoblasts are incubated with MWCNTs or carbon black. After culture for 3 weeks, the degree of calcification is very high in the 50 μg mL(-1) MWCNT group. Transmission electron microscopy shows needle-like crystals around the MWCNTs, and diffraction patterns reveal that the peak of the crystals almost coincides with the known peak of HA.

Bony Landmarks of the Anterior Cruciate Ligament Tibial Footprint A Detailed Analysis Comparing 3-Dimensional Computed Tomography Images to Visual and Histological Evaluations

Background: Although the importance of tibial tunnel position for achieving stability after anterior cruciate ligament (ACL) reconstruction was recently recognized, there are fewer detailed reports of the anatomy of the tibial topographic footprint compared with the femoral side. Hypothesis: The ACL tibial footprint has a relationship to bony prominences and surrounding bony landmarks. Study Design: Descriptive laboratory study. Methods: This study consisted of 2 anatomic procedures for the identification of bony prominences that correspond to the ACL tibial footprint and 3 surrounding landmarks: the anterior ridge, lateral groove, and intertubercular fossa. In the first procedure, after computed tomography (CT) was performed on 12 paired, embalmed cadaveric knees, 12 knees were visually observed, while their contralateral knees were histologically observed. Comparisons were made between macroscopic and microscopic findings and 3-dimensional (3D) CT images of these bony landmarks. In the second procedure, the shape of the bony prominence and incidence of their bony landmarks were evaluated from the preoperative CT data of 60 knee joints. Results: In the first procedure, we were able to confirm a bony prominence and all 3 surrounding landmarks by CT in all cases. Visual evaluation confirmed a small bony eminence at the anterior boundary of the ACL. The lateral groove was not confirmed macroscopically. The ACL was not attached to the lateral intercondylar tubercle, ACL tibial ridge, and intertubercular space at the posterior boundary. Histological evaluation confirmed that the anterior ridge and lateral groove were positioned at the anterior and lateral boundaries, respectively. There was no ligament tissue on the intercondylar space corresponding to the intercondylar fossa. In the second investigation, the bony prominence showed 2 morphological patterns: an oval type (58.3%) and a triangular type (41.6%). The 3 bony landmarks, including the anterior ridge, lateral groove, and intertubercular fossa, existed in 96.6%, 100.0%, and 96.6% of the cases, respectively. Conclusion: There is a bony prominence corresponding to the ACL footprint and bony landmarks on the anterior, posterior, and lateral boundaries. Clinical Relevance: The study results may help create an accurate and reproducible tunnel, which is essential for successful ACL reconstruction surgery.

A thin carbon-fiber web as a scaffold for bone-tissue regeneration.

Due to the rapid progress being made in tissue regeneration therapy, biomaterials used as scaffolds are expected to play an important role in future clinical application. We report the development of a 3D web (sheet) consisting of high-purity carbon fibers in a nanoscale structure. When the thin carbon-fiber web (TCFW) and recombinant human bone morphogenetic protein 2 (rhBMP-2) composite is implanted in the murine back muscle, new ectopic bone is formed, and the values of the bone mineral content and bone mineral density are significantly higher than those obtained with a collagen sheet. Observation of the interface between the carbon fibers and bone matrix reveal that the fibers are directly integrated into the bone matrix, indicating high bone-tissue compatibility. Further, the rhBMP-2/TCFW composite repairs a critical-size bone defect within a short time period. These results suggest that the TCFW functions as an effective scaffold material and will play an important role in tissue regeneration in the future.

Basic potential of carbon nanotubes in tissue engineering applications

Carbon nanotubes (CNTs) are attracting interest in various fields of science because they possess a high surface area-to-volume ratio and excellent electronic, mechanical, and thermal properties. Various medical applications of CNTs are expected, and the properties of CNTs have been greatly improved for use in biomaterials. However, the safety of CNTs remains unclear, which impedes their medical application. Our group is evaluating the biological responses of multiwall CNTs (MWCNTs) in vivo and in vitro for the promotion of tissue regeneration as safe scaffold materials. We recently showed that intracellular accumulation is important for the cytotoxicity of CNTs, and we reported the active physiological functions CNTs in cells. In this review, we describe the effects of CNTs in vivo and in vitro observed by our group from the standpoint of tissue engineering, and we introduce the findings of other research groups.