Week 1 HW: Final Project Ideas

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1. What do you want to make?

A biomaterial based prosthetic liner which addresses the current problem of volume changes in residual limb. It aims to resolve the problem at the material level itself and eliminate the need for manual adjustments. By sensing a biological signal at the skin surface, the material will expand or contract to provide a snug fit of the prosthetic. Various bio-signals like changes in limb temperature, pH shift of the limb etc. need to be explored to identify which gives a better biomaterial reaction to improve the prosthetic fit at any given time.

Currently, the problem is addressed by adding or removing stump socks, pads, inflatable air bladders, and fluid-filled bladders. Some prosthetics come with smart electronics, mechanical knobs or pneumatic systems which help in adjusting the socket size. But these solutions add additional mechanisms to the liner or the prosthetic Instead the biomaterial which I intend to make aims to solve the problem at the liner level itself, thus aiming to eliminating the need for additional adjustments.

Studies have shown that post operative changes in residual volume tend to delay the prosthetic fitting. Early fitting of prosthetic has advantages like normal gait re-education and active physical training leading to a more independent life. It also has psychological advantages such as better acceptance of the amputation and restoration of body image. Having a self adjusting biomaterial will help in fitting prosthetics on time and helping amputees with their recovery journey.

My inclination towards working on prosthetics comes from my previous experience of working on a project related to designing physical activity toys for children with hand spasticity due to cerebral palsy. That project exposed me to various problems like brace fit issues, brace related chafing, restricted movements etc. All this time I had been looking at braces, prosthetics etc. as static mechanical objects but this course has introduced me to a new avenue of possibility of considering biomaterials with bio-manufacturing. I am keen to explore how bio-manufacturing can help in resolving existing issues related to limb rehabilitation.

2. What living system could make it?

Microbial system like using bacteria E.coli can be used as a living system for bio-manufacturing. It will be used to produce required protein which can turn into an expanding and contracting bio-material. This elastin like polypeptide (ELP) will be designed to undergo a reversible structural transition in response to changes in pH or temperature.

The E.coli used in the process must be engineered to contain DNA which can encode a desired protein in suitable growth conditions. The DNA sequence will determine and influence protein properties like responsiveness and transition. As the E.coli grows, DNA undergoes transcription to RNA and RNA translates to ELP. This protein needs to be harvested and purified before next steps. The purified ELP could be cross-linked into a hydrogel, film or fibrous structure. The outcome of this process will be a bacterially manufactured protein based bio-material designed to expand and contract based on surrounding environmental parameters.

The assumptions in this process is that sufficient amount of protein can be extracted from the bacterial system and the processed biomaterial will be stable at room temperature and will retain its environmental stimulus responsive behaviour. The exact magnitude and speed of expansion and contraction needs to be validated based on suitable factors for the usage.

3. How could automation help you make it?

Automation will speed up the overall process, improve accuracy and allow repeatability of experiments. As the biggest unknown is the ELP design which will give the desired result, automation can help in running multiple variations of experiments.

A liquid handling robot such as an Opentrons can help conduct these tests in a controlled environment. The robot could repeat the test by varying the ELP concentrations and preparing samples. Using a measuring instrument and method, I can measure the magnitude of expansion and contraction, material response speed, maximum number of cycles of repeated transitions and any other property which can help in understanding the success of the biomaterial. 

As I have not determined which bio-signal will be the best stimulus for the transition of the bio-material, robot can test the bio-material response under various pH levels and externally varying temperature settings to see if different combinations of stimuli can give better results. This all can be done in a systematic and planned manner using robot automation and required equipment.

4. What would it take to make it at a meaningful scale?

As a part of first batch of production I would go with the example of targeting 1000 people. This will be useful as this is a considerable production size to understand any mass manufacturing constraints and scalability of the overall product.

One of the studies mentioned that the average weight of a conventional liner is 450gm and personalised lightweight liner is 107.3 gm. If I take an average of this as 280gm and proceed to calculate based on my first batch production of 1000 liners, I will need material of 280kg. But the entire 280kg will not be ELP, the final material may contain other structural materials. At this stage, I cannot calculate the quantity of ELP required because that will be based on the outcome of various tests. Based on that I would be able to determine the percentage of ELP in this 280gm of one liner.

For manufacturing the first batch I would look beyond liquid handling robot and consider bioreactors which can be automated as well to support the production as per one of the studies.

5. What you don’t know yet?

Bio-signal

  • Which bio-signals are associated with the changes in residual limb volume?
  • Which bio-signal can be a reliable stimulus for the biomaterial?

ELP responsiveness

  • Is the responsiveness produced by ELP enough in terms of volume?
  • How quickly can the bio-material respond to the stimulus?
  • Which environmental factors can impact responsiveness?
  • How many cycles of expansion and contraction can the material undergo?

ELP percentage

  • Which is the appropriate percentage ratio of ELP and structural material which will give a desired outcome?
  • How does ELP percentage impact all factors related to responsiveness?

References

Richardson A, Dillon MP. User experience of transtibial prosthetic liners: A systematic review. Prosthetics and Orthotics International. 2017;41(1):6-18. https://doi.org/10.1177/0309364616631343

Hester, J., & Shepherd, M. (2026). Temperature and moisture management and mitigation techniques in prosthetic sockets and liners: A rapid review. Prosthetics and orthotics international, 10.1097/PXR.0000000000000535. Advance online publication. https://doi.org/10.1097/PXR.0000000000000535

Sanders, J. E., & Fatone, S. (2011). Residual limb volume change: systematic review of measurement and management. Journal of rehabilitation research and development, 48(8), 949–986. https://doi.org/10.1682/jrrd.2010.09.0189

Sanders, J. E., Allyn, K. J., Harrison, D. S., Myers, T. R., Ciol, M. A., & Tsai, E. C. (2012). Preliminary investigation of residual-limb fluid volume changes within one day. Journal of rehabilitation research and development, 49(10), 1467–1478. https://doi.org/10.1682/jrrd.2011.12.0236

Paternò, L., Ibrahimi, M., Rosini, E., Menfi, G., Monaco, V., Gruppioni, E., Ricotti, L., & Menciassi, A. (2021). Residual limb volume fluctuations in transfemoral amputees. Scientific reports, 11(1), 12273. https://doi.org/10.1038/s41598-021-91647-9

Wang, W., Yao, L., Cheng, C. Y., Zhang, T., Atsumi, H., Wang, L., Wang, G., Anilionyte, O., Steiner, H., Ou, J., Zhou, K., Wawrousek, C., Petrecca, K., Belcher, A. M., Karnik, R., Zhao, X., Wang, D. I. C., & Ishii, H. (2017). Harnessing the hygroscopic and biofluorescent behaviors of genetically tractable microbial cells to design biohybrid wearables. Science advances, 3(5), e1601984. https://doi.org/10.1126/sciadv.1601984

Liu S and Xu W (2020) Engineered Living Materials-Based Sensing and Actuation. Front. Sens. 1:586300. doi: 10.3389/fsens.2020.586300

Trabbic-Carlson, K., Setton, L. A., & Chilkoti, A. (2003). Swelling and mechanical behaviors of chemically cross-linked hydrogels of elastin-like polypeptides. Biomacromolecules, 4(3), 572–580. https://doi.org/10.1021/bm025671z

Kowalczyk, T., Hnatuszko-Konka, K., Gerszberg, A., & Kononowicz, A. K. (2014). Elastin-like polypeptides as a promising family of genetically-engineered protein based polymers. World journal of microbiology & biotechnology, 30(8), 2141–2152. https://doi.org/10.1007/s11274-014-1649-5

Mackay, J. A., Callahan, D. J., Fitzgerald, K. N., & Chilkoti, A. (2010). Quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides. Biomacromolecules, 11(11), 2873–2879. https://doi.org/10.1021/bm100571j

MacEwan, S. R., & Chilkoti, A. (2014). Applications of elastin-like polypeptides in drug delivery. Journal of controlled release : official journal of the Controlled Release Society, 190, 314–330. https://doi.org/10.1016/j.jconrel.2014.06.028

de Haas, R. J., Ganar, K. A., Deshpande, S., & de Vries, R. (2023). pH-Responsive Elastin-Like Polypeptide Designer Condensates. ACS applied materials & interfaces, 15(38), 45336–45344. https://doi.org/10.1021/acsami.3c11314

Paternò, L., Dhokia, V., Menciassi, A., Bilzon, J., & Seminati, E. (2020). A personalised prosthetic liner with embedded sensor technology: a case study. Biomedical engineering online, 19(1), 71. https://doi.org/10.1186/s12938-020-00814-y

AI prompts (ChatGPT and Claude)

  • Find research papers about issues with using liners with prosthetics.
  • Which living systems have the ability to turn into an expanding and contracting biomaterial?
  • What is ELP and how can it have reversible properties?
  • Explain bio-manufacturing automation.
  • Get research paper related to ELP production and explain the overall concept.