Date: 22nd July 2021
Self-healing materials hold great promise in the field of biomedical engineering. However, many require an external stimulus such as heat or UV light to facilitate the process of self-healing, which are harmful to the body. This has made in vivo applications therefore challenging, and their use to date has been limited. Now, researchers have designed a series of biodegradable and biocompatible self-healing elastomers (SHEs) with tunable mechanical properties, and have applied and validated them in three disease models in vivo, offering a new and promising therapeutic strategy for aortic aneurysm, nerve coaptation and bone immobilisation.
One of the most basic techniques in traditional surgery is suturing, and it is a crucial part of many surgeries. However, it requires expertise, is repetitive and time consuming, and whilst there has been a significant move towards minimally invasive surgery in recent years, it is extremely difficult to suture in a such narrow surgical field.
Self-healing materials could provide a solution to this problem and elastomers which have been incorporated into heart assistance devices and medical catheters have been widely used in biomedicine owing to their biomimetic mechanical properties in soft tissue. Therefore, biocompatible and biodegradable self-healing elastomers (SHEs), which have yet to be used in biomedical applications, may hold great potential in the field.
Now, researchers at Shanghai Jiao Tong University and Donghua University, China, led by Xiaofeng Ye, Zhengwei You and Qiang Zhao have designed and fabricated a family of mechanically tunable, biocompatible and biodegradable SHEs for biomedical applications. Using them to correct haemodynamics, improve endothelial function and limit the progress of aneurysms, using them for nerve coaptation, and replacing metal wires with a biodegradable SHEs to achieve sternum immobilisation.
The team first synthesised and characterised the dimethylglyoxine-urethane-based polyurethane elastomers (or SHEs). The mechanical tunability was achieved by adjusting the degree of crosslinks resulting in hard of softer properties. Two separates sheets or ends of the SHEs were able to self-heal upon external pressure at room temperature, and were also found to be biodegradable.
The first in vivo test was SHEs for aneurysms. These are often considered as ticking time bombs that put patient’s lives at risk and are difficult to treat. Luminal dilation of aneurysms cause the haemodynamic flow of blood to be turbulent, leading to endothelial cell dysfunction and aneurysm expansion. The team here explored the SHEs to limit the progress of aneurysms in mice models.
The SHEs were wrapped around the aneurysm and achieved in situ seamless sleeving for support. Haemodynamic flow was restored, endothelial function was improved, and the progress of the aneurysms was limited. Neovascularization and apoptosis of vascular smooth muscle cell was reduced in the SHE cohort as was the level of inflammation.
Next, the team investigated SHEs use for nerve coaptation. Severed sciatic nerves were wrapped with SHEs, then both ends brought together for self-healing using a ‘Lego’ brick approach. The time required for coaptation operation with SHE was shortened by 3/4 compared to that required for traditional suturing. The recovery of nerves was more efficient than that in the suture group, evident by histology and gait analysis.
Lastly, the team wanted to assess SHEs for bone immobilisation. After thoracotomy, steel wire fixation of the sternum is the most popular method for stabilisation, but it is an imperfect procedure, and can cause hypersensitivity to the nickel in the wire. The fractured sternums healed together at 6 weeks post-surgery using SHEs immobilisation, and exhibited continuous cortical bone reflecting healing.
Conclusions and future applications
The team here have established a new family of SHEs, and pioneered the use of the self-healing properties of materials for in vivo applications. Self-healing can be achieved at room temperature, and the mechanical properties of the SHEs can be readily tuned by controlling the degree of crosslinking, allowing tailoring of SHEs specifically for different types of tissue (soft and hard).
In the future, the team plan to engineer SHEs focusing on bionic mechanics, hoping to utilise SHEs to meet more needs in orthopaedic diseases or injuries such as disorders of the tendon calcaneus or intervertebral disc. SHEs offer a new promising aneurysm therapy, and the study has paved the way for the development of self-healing material in a clinical context.
Whilst, the power of SHEs is highlighted here with their in vivo use, other self-healing materials are also addressing other research challenges. Bioprinting holds much promise for regenerative medicine, addressing the urgent need for tissues and organs suitable for transplantation. A major challenge for bioprinting is the formation of complex-shaped arrangements and the retention of shape for these bioprinted constructs. Scientists have recently used self-healing yield-stress biogels to enable the self-assembly of spheroids for tissue fabrication. Such bioprinted tissue, could be advanced by the use of SHEs as a replacement to suturing on transplantation into the body. The continued development of self-healing material will be an important one, and will likely apply to many different areas of research and biomedical engineering.
Jiang, C., Zhang, L., Yang, Q., Huang, S., Shi, H., Long, Q., Qian, B., Liu, Z., Guan, Q., Liu, M., et al. (2021). Self-healing polyurethane-elastomer with mechanical tunability for multiple biomedical applications in vivo. Nature Communications 12, 4395.
https://doi.org/10.1038/s41467-021-24680-x
