The Jiandong Ding’s research group at Fudan University has, in collaboration with Lifetech Scientific Corporation, achieved the  industrial production of medical grade expanded polytetrafluoroethylene（ePTFE）. This is the first time for industrialization of high-performance medical ePTFE used in stent-graft in China.

ePTFE is very useful in biomedical fields such as covered stents and plastic surgery owing to its excellent biocompatibility and mechanical properties. However, ePTFE material prepared by the traditional biaxial stretching process is with thicker middle and thinner sides due to the bowing effect, which poses a major problem in industrial-scale fabrication. To solve this problem, Ding’s team has designed an olive-shaped winding roller to enable the middle part of the ePTFE tape a greater longitudinal stretching amplitude than the two sides, so as to make up for the excessive longitudinal retraction tendency of the middle part when it is transversely stretched. A series of physicochemical performance characterization and biological evaluation conducted according to international standards have confirmed excellent performance and biocompatibility of the improved ePTFE membrane produced on an industrial scale, fully meeting the requirements of medical grade raw materials.

Polytetrafluoroethylene (PTFE) was invented by DuPont in 1938. In 1969, Gore Company invented expanded polytetrafluoroethylene (ePTFE). Given the excellent biocompatibility of PTFE and the combination of good mechanical strength and suitable flexibility, ePTFE is unique in medical devices such as implanted stent-grafts. China has always been in a blank in this crucial medical raw material. Herein, Professor Ding Jiandong's team from Fudan University collaborated with LifeTech Scientific Corporation to achieve a breakthrough in China's industrial production of medical grade ePTFE.

Following the biaxial stretching strategy, the team has built a complete set of industrial equipment, with the basic principle schematically shown in Figure 1.

Figure 1. Schematic presentation of PTFE and ePTFE used for a medical device.

The main facility is shown in Figure 2.

Figure 2. The manufacturing process of ePTFE membrane. The standing person in Figure 2g is the corresponding author of the article.

The team has also designed a novel olive roller to improve the traditional technology, as shown in Figure 3. As a result, the ePTFE membrane stretched transversely with olive rollers exhibited significantly higher uniformity than the membrane prepared with common rollers. The higher uniformity of the membrane can decrease the probability of structural damage and provide longer service life.

Figure 3. Diagram of using an olive roller to roll up the PTFE tape in the longitudinal stretching and then roll down in the transverse stretching to reduce the “bowing effect” with the longitudinal contraction of the ePTFE membrane when both sides grasped by the clips.

In the study, it has also been confirmed that the addition of lubricants is conducive to improving the performance of the ePTFE membrane. Nevertheless, overly more lubricants led to the decline of the tensile strength of the ePTFE membrane. Hence, an appropriate amount of lubricant is required.

When the longitudinal stretching ratio increased, the orientation along that direction increased and the longitudinal strength increased. The influence of transverse stretching ratio on longitudinal tensile strength was found to be twofold. The transverse tensile force promoted the formation of fibers in the three-dimensional network and improved the overall strength of the membrane, beneficial to the longitudinal strength. However, when the transverse stretching reached a certain extent, the longitudinal fibers were gradually consumed by the formation of branching fibers in other directions, resulting in fewer fibers along the longitudinal direction and finer fibers.

Sintering temperature is another key parameter to control the quality of ePTFE. The nodes of the resultant ePTFE film depended on sintering temperature, as shown in Figure 4. The higher the temperature, the higher the fraction of crystalline zone transformed into amorphous zone. Larger nodes and stronger fibrils improved the strength of the membrane. However, over-sintering also led to the reduction of the uniformity of pore size, and even breaking of the fibrils.

Figure 4. Effects of sintering temperature on properties of ePTFE membrane.

  According to the biological assessment following the protocols of ISO 10993, the sintered ePTFE membrane did not exhibit adverse phenomena such as accelerated coagulation, elevated body temperature, sensitization, and intradermal stimulation. The histopathological examination of animals also showed that the sintered ePTFE membrane did not cause excessive inflammatory reaction and could fit with muscle tissue, which further proved the biocompatibility of the obtained product.

In summary, this study has, using self-built apparatus, achieved the production of medical ePTFE membranes with excellent performance and good biocompatibility on an industrial scale. The ePTFE membrane might be applied not only in implanted stent-grafts, but also in other aspects such as artificial blood vessels, biological patches, and electronic equipment.

This article was published in the journal Regenerative Biomaterials. The first author is Gang WANG, a core R&D engineer at LifeTech Scientific corporation and a candidate of Doctor of Engineering at Fudan University. The corresponding author is his supervisor Prof. Jiandong DING, who is the director of the State Key Laboratory of Polymer Molecular Engineering and a distinguished professor of Fudan University. See please: Gang Wang, Yusheng Feng, Caiyun Gao, Xu Zhang, Qunsong Wang, Jie Zhang, Hongjie Zhang, Yongqiang Wu, Xin Li, Lin Wang, Ye Fu, Xiaoye Yu, Deyuan Zhang, Jianxiong Liu, Jiandong Ding*, Biaxial stretching of polytetrafluoroethylene in industrial scale to fabricate medical ePTFE membrane with node-fibril microstructure, Regenerative Biomaterials, Volume 10, 2023, rbad056.

Article link: https://doi.org/10.1093/rb/rbad056