Promising Polymers to For a Successful Transplant
By: Hadeel Saab
Scientists have brought considerable ingenuity into creating biomedical devices to help treat various conditions and diseases like T1D. However, as clever as these devices may be, an all-too-common difficulty across all these creative applications is overcoming bodily rejection once implanted, as discussed in a previous TSS woven. Hydrogels, water-swollen networks of varying polymers, are popularly used for biomedical applications. With the great versatility in hydrogels’ formation comes the ability to tailor to the extremely specific and complex needs of different applications, such as cell encapsulation, tissue regeneration and drug delivery.
One group of researchers from MIT, Harvard and Boston Children’s Hospital did just this, leveraging the design flexibility of hydrogels formed from the natural material alginate, a popular choice for its long studied and well known properties. With the goal of finding hydrogel combinations that reduced negative foreign body response (fibrosis), the researchers synthesized and analyzed a 774-membered alginate analog library. They were able to whittle down their search to three successful analogs in order to conduct more extensive analyses. Here’s what they discovered for all three hydrogel alginate analogs:
- In vivo experiments with microcapsules of the three analogs inserted subcutaneously in rodents and non-human primates at multiple sites showed reduced levels of fibrosis for at least six months.
- Cellular staining and confocal microscopy of microcapsules showed little to no presence of macrophages, fibroblasts and general cellular deposition compared to the control.
- All three analogs were triazole derivatives, suggesting that this class of molecules may have a special ability to fend off fibrotic processes by modulating immune cells.
In terms of T1D, this discovery of biomaterials that inhibit fibrotic processes is crucial for the long-term health and safety of pancreatic islet cell transplantation. There are other limitations that must be addressed, one being the loss of the islets’ microenvironment and extracellular matrix (ECM) during the isolation procedure of the transplantation. Thus, in addition to fighting off fibrosis, the transplanted cell must have expanded functionality to mimic the ECM.
At the University of Pennsylvania, researchers investigated interpenetrating polymer networks (IPN) as an option to enhance biopolymer hydrogel functionality in many ways and thus more seamless transplantation. IPN hydrogels are able to specifically address the challenges of standard single network hydrogels such as weak mechanics, static properties and lack of full integration with the cellular environment.
- IPN hydrogels are characterized by the combination of independent, yet interdigitating polymer networks at the cellular level.
- IPN hydrogels offer even greater design flexibility to create “smart” hydrogels that are engineered to respond to physical or chemical stimuli as well as pure mechanical strength.
- Interestingly enough, alginate is a great base material for crosslinking in IPN hydrogels.
Putting the pieces together
Given these two studies, we see that there are many angles of research for hydrogel functionality. If researchers are able to clinically translate these findings for overcoming limitations of inharmony with the cellular environment and immune system, beta cell islet transplantation for patients with type 1 diabetes will become a much more viable option.
- Vegas, A. J., Veiseh, O., Doloff, J. C., Ma, M., Tam, H. H., Bratlie, K., … & Fenton, P. (2016). Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nature biotechnology, 34(3), 345-352.
- Dhand, A. P., Galarraga, J. H., & Burdick, J. A. (2020). Enhancing Biopolymer Hydrogel Functionality through Interpenetrating Networks. Trends in Biotechnology.