An engineer is trained to solve problems through science and math. We can see engineers everywhere in our lives, such as civil engineers, chemical engineers, electrical engineers, and software engineers, to improve our daily lives. What can engineers do in the biomedical field? A pioneer, professor Robert Langer, an internationally well-known biomedical engineer and inventor, is a perfect example illustrating how engineers can contribute to biomedical science. Dr. Langer holds the title of David H. Koch Institute Professor at the Massachusetts Institute of Technology (MIT) as well as that of Senior Lecturer on Surgery at Harvard University’s Medical School. It is worth to mention that being an Institute Professor at MIT is the highest honor that can be awarded to a faculty member. Besides, Dr. Langer has more than 1,500 published papers and over 1,400 issued patents and pending patents worldwide. In his research, he focuses on solving biomedical problems from an engineering aspect, such as developing materials for drug delivery, cell engineering, and tissue engineering. Here we have some examples to demonstrate how engineers contribute to the field.
First, Dr. Langer and his colleagues with Bill & Melinda Gates Foundation created pulsatile-release PLGA microspheres for single-injection vaccination1 for developing world. Poly (lactic-co-glycolic acid) (PLGA) is an FDA-approved degradable material for clinical application, and core-shell decoupled microspheres are fabricated by a new microfabrication method (StampEd Assembly of polymer Layers (SEAL))2. Despite the immense increase in vaccine coverage worldwide over decades, vaccine-preventable infectious diseases still claim the lives of approximately 1.5 million children every year because of inadequate distribution and administration of vaccines in the developing countries. Currently, around 19.4 million infants do not receive fully immunized against diphtheria, tetanus, and pertussis. Moreover, 6.6 million of them with one dose of the vaccine remain at risk for these diseases due to lack of full series of doses. With the pulsatile-release PLGA microspheres and SEAL technology, the problem of inadequate distribution and administration of vaccine could be solved, and millions of people in the developing world would benefit.
Fig. 1, Using different molecular weight of PLGA to control degradation time to release the therapeutics to evoke immune response. (modified from McHugh, K. J. et al. Science, 2017).
Second, Dr. Langer and his colleagues discovered three chemical materials which can suppress foreign body response to minimize fibrosis in rodents and at least 6 months in non-human primates3. These materials were conjugated to alginate hydrogel, and these hydrogel microspheres were transplanted in mice and monkeys. In addition, these anti-fibrotic materials could be applied in cell therapy, such as beta cell replacement treatment for type I diabetes. In type I diabetes, patients’ pancreatic islet cells are destroyed by their own immune system. To date, the most common treatment is a daily insulin injection to control blood glucose. However, insulin injection cannot cure type I diabetes or prevent the many devastating diseases associated with diabetes, such as blindness, hypertension, and kidney disease. Islet cell transplantation could provide an alternative treatment for type I diabetes to avoid daily injection and restore normoglycemia. However, foreign body response is a major challenge for cell therapy. The cellular and collagenous deposition would isolate the transplanted device from the host, which could induce tissue distortion, cut off the nourishment of encapsulated cells, and finally lead to device failure. With these new anti-fibrotic materials, the transplanted device with insulin-producing beta cells could maintain its function in the long term to cure type I diabetes.
Fig. 2, Three chemical materials can suppress foreign body response to minimize fibrosis in rodents and non-human primates. Encapsulated by these materials, the therapeutic cells can be protected from host immune system and also suppress its immune system to reduce foreign body response.
Third, Dr. Langer’s group developed a combinatorial library of ionizable lipid-like materials to identify mRNA delivery vehicles that facilitate mRNA delivery in vivo and provide potent and specific immune activation4. The cationic lipid-like materials could encapsulate therapeutic mRNA in lipid nanoparticles by electrostatic interaction. To date, mRNA therapeutics is a promising strategy for disease treatment and vaccination. In contrast to DNA therapeutics, mRNA delivery results in transient expression of encoded proteins, and so avoids complications associated with insertional mutagenesis. Currently, mRNA therapeutics, including disease treatment and vaccination, are in the process of clinical trials. For instance, TranslateBio has conducted phase ½ clinical trials in delivering mRNA encoding fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to treat cystic fibrosis by nebulization. For COVID-19, Moderna (co-founded by Dr. Langer) and Pfizer all utilize lipid nanoparticles to deliver mRNA encoding for a prefusion stabilized form of spike protein. Moderna also has two mRNA cancer vaccines in phase 1 and phase 2 to target solid tumors and melanoma. These clinical trials with mRNA delivery are incorporated to cationic lipid-like materials to enhance mRNA stability and lead to an increase in intracellular protein expression.
Fig. 3, Illustration for the formulation of lipid nanoparticles in mRNA delivery
In sum, biomedical engineering is a combination of multiple disciplines, such as engineering, biology, medical science, and chemistry. To date, biomedical engineers have contributed to the biomedical field in different aspects, such as new materials, fabrication methods, and medical devices to improve current medical treatments and solve emerged medical problems, for instance, COVID-19.
1. Guarecuco, R. et al. Immunogenicity of pulsatile-release PLGA microspheres for single-injection vaccination. Vaccine 36, 3161–3168 (2018).
2. McHugh, K. J. et al. Fabrication of fillable microparticles and other complex 3D microstructures. Science (80-. ). 357, 1138 LP – 1142 (2017).
3. Vegas, A. J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345 (2016).
4. Miao, L. et al. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019).
Jason(Yen-Chun) Lu, All right reserved.