Advancing Biopharmaceutical Innovation Through Cell Encapsulation and Biomimetic Therapeutic Systems

1. What first drew you to the field of biopharmaceutical engineering, and how did your interest in biomimetic oxygen therapeutics and cell encapsulation develop?

My interest in biopharmaceutical engineering began during my senior year as an undergraduate. For my capstone project, I worked on the encapsulation of bioactive ingredients from traditional Chinese medicine for controlled release, which introduced me to biomaterials and drug delivery systems. During my master's studies, I conducted research in an orthopaedic laboratory at a hospital, where I entered the field of biopharmaceutical engineering by developing microencapsulation systems for bone marrow-derived mesenchymal stem cells (BM-MSCs) to achieve controlled and sustained release of growth factors for bone tissue engineering. To further pursue this research direction, I changed my major from Food Science and Engineering to Biomedical Engineering during my Ph.D., focusing on biopharmaceuticals, cell engineering, and tissue engineering. My interest in biomimetic oxygen therapeutics developed later when I worked with my first group of capstone students and unexpectedly discovered a red blood cell-shaped hydrogel carrier. This serendipitous finding led us to explore biomimetic oxygen therapeutics that mimic both the morphology and function of human red blood cells.

2. What are the key advantages of using encapsulated therapeutic cells compared to traditional drug delivery systems?

The major advantages of encapsulated therapeutic cells are their ability to provide long-term, controlled secretion of therapeutic molecules without repeated drug administration. Unlike conventional drug delivery systems that release a finite amount of drug, encapsulated living cells continuously produce therapeutic proteins in response to physiological signals from the host. For example, encapsulated pancreatic islets or β-cells can be protected from immune attack while continuously secreting insulin in response to blood glucose levels, providing a promising treatment for Type 1 diabetes.

3. How do encapsulation matrices help protect transplanted cells from immune rejection while maintaining their biological function?

Encapsulation matrices are typically semi-permeable, allowing the diffusion of small molecules such as oxygen, nutrients, waste products, and therapeutic molecules secreted by the encapsulated cells. At the same time, they prevent large immune molecules, antibodies, and immune cells from entering the capsule, thereby protecting the transplanted cells from immune rejection while maintaining their biological function.

4. What are the most significant scientific or engineering challenges currently limiting the clinical translation of cell encapsulation technologies?

One of the biggest challenges is designing encapsulation systems that are sufficiently biocompatible to minimise fibrosis while allowing adequate transport of oxygen and nutrients to maintain long-term cell viability. At the same time, the encapsulated cells must remain protected from the host immune system. Other major challenges include obtaining reliable cell sources, scalable cell manufacturing, consistent therapeutic dosing, and regulatory compliance. For macroencapsulation devices, achieving sufficient vascularisation is also critical to ensure long-term survival and function of the encapsulated cells.

5. Your research includes biomimetic oxygen therapeutics. How does oxygen delivery intersect with cell-based drug delivery systems in your work?

My research on biomimetic oxygen therapeutics aims to develop red blood cell-inspired carriers that mimic the oxygen transport function, biconcave shape, size, and deformability of natural erythrocytes. I see these technologies as complementary, improved oxygen delivery can enhance the survival, function, and long-term efficacy of encapsulated therapeutic cells, particularly in poorly vascularized tissues.

6. Can you share an example where controlled or sustained release of bioactive agents significantly improved therapeutic outcomes?

One good example is the use of encapsulated genetically engineered cells that continuously release neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) or ciliary neurotrophic factor (CNTF) for neurodegenerative diseases. Compared with repeated administrations, sustained local secretion maintains therapeutic concentrations for extended periods, reduces systemic exposure and treatment frequency, and has demonstrated improved neuronal survival and functional outcomes in preclinical studies.

7. How do you approach balancing cell viability with controlled release performance when designing encapsulation systems?

Balancing cell viability with controlled release performance requires optimising both the biological and material aspects of the encapsulation system. Encapsulated cells must receive sufficient oxygen and nutrients to maintain long-term viability, while material properties such as pore size, crosslinking density, and capsule geometry are tuned to achieve the desired release profile without compromising mass transport. The final design is refined through iterative evaluation of both cell function and release kinetics.

8. With over 50 publications and a book on controlled drug delivery, what major shifts have you observed in the field over the past decade?

The field has evolved rapidly over the past decade. Early efforts focused primarily on preventing immune rejection, whereas current research emphasises improving long-term cell viability, enhancing biomaterial biocompatibility to reduce fibrosis, and engineering cells for controlled, on-demand therapeutic protein secretion. Advances in stem cell technologies, gene editing, and smart biomaterials have greatly expanded the range of diseases that can be targeted. Overall, the field is moving toward more personalised, scalable, and clinically translatable encapsulated cell therapies.

9. What role do you see biopharmaceutical encapsulation technologies playing in next-generation precision medicine?

I believe cell encapsulation technologies will become an enabling platform for precision medicine because they provide localised, sustained, and personalised delivery of biologics. Combined with advances in stem cell engineering and gene editing, encapsulated cells can be tailored to individual patients and designed to release therapeutics in response to specific physiological or disease signals. This approach has the potential to improve treatment efficacy, reduce systemic side effects, and transform the management of chronic diseases and regenerative therapies.

10. How do you envision scaling up these technologies for industrial or clinical manufacturing while maintaining consistency and safety?

Scaling up requires optimisation of both cell manufacturing and the encapsulation process. Cells can be expanded efficiently using advanced three-dimensional culture systems, such as microcarrier-based bioreactors. For encapsulation, scalable technologies such as multi-nozzle electrospray systems enable high-throughput production. Maintaining consistency requires a comprehensive characterisation of both cells and biomaterials throughout manufacturing, while ensuring sterility, product quality, and batch-to-batch reproducibility. Ultimately, successful clinical translation depends on manufacturing processes that fully comply with current Good Manufacturing Practice (cGMP) standards.
 
11. What advice would you give young researchers entering the field of biomaterials and biopharmaceutical delivery systems today?

I would encourage young researchers to develop a strong interdisciplinary background spanning biology, materials science, engineering, and medicine. Stay curious, embrace collaboration, and cultivate an entrepreneurial mindset. It is important not only to develop innovative biomaterials but also to think about scalability, manufacturability, regulatory requirements, and clinical applicability from the beginning. Keeping patient needs and clinical translation in mind will help ensure that research ultimately has a real-world impact.