Hideyuki Sakoda

Microneedle arrays (MNAs) consisting of numerous tiny needles have attracted considerable attention for selective intradermal and subcutaneous delivery of pharmaceutical agents. Since reliable skin puncture and insertion are essential for dose control, applicators that push MNAs into the skin using springs or other mechanisms have been extensively researched. The puncture and insertion capabilities of an MNA depend on the compressive load generated when it is pressed against the skin. The compressive load is considered to be influenced not only by the MNA per se and the application method, but also by the structures and mechanical properties of the biological tissues at the application site. Nevertheless, most previous studies on evaluating the puncture and insertion abilities of MNAs did not consider the impact of subcutaneous soft tissues. In this study, the compressive loads generated by an applicator were measured at various sites of the body in 15 healthy adults. We used a proprietary test applicator that employed a spring to impact the skin at high speed, and a system that can measure the short-term load generated during impact. Furthermore, the structures and mechanical properties of the skin and subcutaneous soft tissues at the same body locations among the 15 individuals were evaluated and correlated with the measured compressive loads. The compressive load induced by the impact varied significantly with location, and correlated highly with the distance to the bone. There was no correlation with age, sex, or body mass index, or with the structure or mechanical properties of the skin. These results indicate that the structure of the subcutaneous tissue has a strong influence on the compression load and the ability to puncture and insert the MNA. The findings of this study can be useful for developing MNAs and applicators, determining their essential physical characteristics, selecting the appropriate administration locations, and developing non-clinical methods for evaluation.

Background: This study aims to investigate the impact of test conditions on the results of the compression testing of microneedle arrays (MNAs). Methods: Uniaxial compression tests were conducted on polyglycolic acid-fabricated biodegradable MNAs. Load–displacement curves were obtained for varying conditions, including the number of microneedles (MNs) compressed simultaneously, compression speeds, and compression angles. Subsequently, the buckling load and stiffness were calculated, and the MN deformation during compression was observed. Results: The buckling load and stiffness per MN decreased significantly with a simultaneous increase in compressed MNs. The mean buckling load and stiffness of 52 MNs in single-needle compression tests were 0.211 ± 0.008 N and 13.9 ± 1.3 N/mm, respectively, with no variation among the three MNAs. However, a significant difference in buckling load and stiffness was observed among the MNs within the MNAs. Additionally, buckling loads and stiffnesses were significantly lower in certain MNs at the same location in different MNAs. Buckling load and stiffness decreased significantly during inclined compression compared to during vertical compression. While the tests evaluate the mechanical properties of MNAs, test results may vary depending on test conditions. Conclusions: Compression testing of the individual MNs comprising an MNA helps evaluate the mechanical properties of MNs and ensure the quality of MNAs.

The delamination of ultra-high molecular weight polyethylene (UHMWPE) in artificial joints is a major cause limiting the long-term clinical results of arthroplasty. However, the conventional test method using simple reciprocation to evaluate the delamination resistance of UHMWPE materials has insufficient detection sensitivity. To reproduce delamination, the unconformity contact must be maintained throughout the test so that the maximum stress is generated below the surface. Therefore, a test method that applies a U-shaped motion comprising two long-linear and one short linear sliding motion was developed. The sensitivity, robustness, and reproducibility of the U-shaped delamination test were investigated and compared with the traditional test method. The traditional test method could reproduce delamination only in materials that had degraded considerably, whereas the U-shaped delamination test could reproduce delamination in a wide range of materials, demonstrating its superior sensitivity. Additionally, using a higher load helped accelerate the test without affecting the test results. The optimal length of the short linear sliding motion was confirmed to be 1 mm. Finally, the inter-laboratory reproducibility of the U-shaped delamination test was confirmed using the round-robin test. The U-shaped delamination test demonstrates high sensitivity, robustness, and reproducibility and contributes to the selection and development of UHMWPE materials and artificial joints with a lower risk of delamination.

Dissolving microneedles (MNs) are novel transdermal drug delivery systems that can be painlessly self-administered. This study investigated the effects of experimental conditions on the mechanical characterization of dissolving MNs for quality evaluation. Micromolding was used to fabricate polyvinyl alcohol (PVA)-based dissolving MN patches with eight different cone-shaped geometries. Axial force mechanical characterization test conditions, in terms of compression speed and the number of compression needles per test, significantly affected the needle fracture force of dissolving MNs. Characterization using selected test conditions clearly showed differences in the needle fracture force of dissolving MNs prepared under various conditions. PVA-based MNs were divided into two groups that showed buckling and unbuckling deformation, which occurred at aspect ratios (needle height/base diameter) of 2.8 and 1.8, respectively. The needle fracture force of PVA-based MNs was negatively correlated with an increase in the needle’s aspect ratio. Higher residual water or higher loading of lidocaine hydrochloride significantly decreased the needle fracture force. Therefore, setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs should contribute to the development and supply of appropriate products.

Poly-ether-ether-ketone (PEEK) and carbon fiber reinforced PEEK as orthopedic implant materials exhibit excellent material properties. Although delamination of PEEK materials has been reported in knee joint wear research, the delamination resistance behavior remains unclear. In this study, the delamination resistance of PEEK materials was investigated; these materials were compared to ultra-high molecular weight polyethylene (UHMWPE). The results of a ball-on-flat type delamination test indicated that the PEEK materials underwent delamination considerably earlier than UHMWPE, and the contact area of the PEEK materials was smaller than that of UHMWPE. Moreover, the indentation modulus, hardness, and coefficient of friction were higher for PEEK materials than for UHMWPE. The reduced tendency of PEEK materials to undergo deformation to mitigate stress concentration at low conformity contact conditions contributed to their inferior delamination resistance compared to that of UHMWPE. The delamination resistance of the PEEK materials was equivalent to that of degraded UHMWPE, which highlights the risk of delamination of PEEK implants in a clinical context. Consequently, when using PEEK materials as an implant component loaded at a low conformity contact condition, the material selection and component design must be carefully considered. Overall, the results of this study can help guide the future development of PEEK-based implants.

Pharmaceuticals reportedly cause damage to some polymeric medical devices that administer them. Because this phenomenon and its causes still remain unclear, in this study, all the possible combinations of polymeric materials and pharmaceutical ingredients that could cause failures were identified by conducting a comprehensive analysis on a wide variety of such combinations and through verification tests using the products. The results of the simple immersion tests and the reports of clinical failures indicated that the failures were not caused by the lack of chemical resistance of the polymers but by the environmental stress cracking (ESC) induced by a combination of the stress generated in the material and the interaction with a specific chemical. Therefore, we evaluated all combinations that could cause ESC by developing and applying a simple method for testing ESC. Polycarbonate and polyethylene terephthalate were found to be damaged by alkaline solutions and oils and fats, and surfactants solutions. These failures were also confirmed by the verification tests. Results from the stress state verification, fractographic analysis, and other studies confirmed that these failures were caused by ESC. Cytotoxicity owing to the induction of ESC was not detected in any combination. These results indicated that the residual stress generated during the manufacturing process was one of the reasons for the failure of the medical devices. This residual stress can be eliminated by employing additional processes such as annealing, thereby preventing medical device failures induced through interactions with pharmaceutical ingredients.

Ultra‐high molecular weight polyethylene (UHMWPE) is used as a bearing surface of joint prostheses and has been reported to absorb lipids such as squalene (SQ) and cholesterol esters in vivo. These lipids have been suggested by in vitro studies using SQ as a model lipid to have the potential to induce polymer degradation. However, the impact of lipid‐induced degradation on the strength and wear resistance of UHMWPE is unknown. In this study, lipid‐induced degradation was simulated by SQ absorption and subsequent accelerated aging, and its influence on the strength and wear resistance of UHMWPE was investigated using wear, fatigue crack growth, and delamination testing. Lipid‐induced degradation was found to have little impact on fatigue crack growth rates and delamination resistance. These results were consistent with previous reports that lipid‐induced degradation is localized near the surface. However, we also found that lipid‐induced degradation increased the wear rate of both non‐crosslinked and crosslinked UHMWPE by a factor of 2.5 and 14, respectively. These results indicate that lipid‐induced degradation may affect the durability and long‐term clinical outcome of joint replacements due to increased wear of UHMWPE.

Ultra‐high molecular weight polyethylene (UHMWPE) is the most popular material used for the articulating surface of joint replacements. Delamination is a common fatigue‐related failure mode in UHMWPE components; however, the relationship between delamination resistance and fatigue crack growth has not been reported. Here, the delamination resistance of contemporary UHMWPE materials, including highly cross‐linked UHMWPE (HXLPE), vitamin E blended UHMWPE (VEPE), and vitamin E blended HXLPE (VEXLPE), was measured to verify a previously proposed accelerated test method using a U‐shaped sliding motion; the results were compared with those of fatigue crack growth tests. The oxidative stability of each material was estimated using Fourier transform infrared analysis. UHMWPE sterilized by gamma irradiation in an inert atmosphere and annealed HXLPE had lower delamination resistance than virgin UHMWPE after artificial aging. This was consistent with previous findings from retrieval studies, and in vitro knee simulator and ball‐on‐flat unidirectional reciprocation wear studies. In contrast, remelted HXLPE, VEPE, and VEXLPE showed excellent delamination resistance after artificial aging. The results of the delamination tests were not consistent with those of fatigue crack growth tests, indicating the complex delamination mechanism and importance of evaluating these factors separately. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 65–72, 2019.