Tailoring Biomaterials for Metabolic Diseases
Authors: Zhen Gu
Journal: Advanced Healthcare Materials (2019)

Metabolic systems consisting of complex networks of chemical reactions and signaling pathways are one of the most fundamental requirements for survival. Highly integrated with the rest of these life-sustaining systems, any dysfunction can lead to a cluster of chronic metabolic disorders, particularly obesity, diabetes, and cardiovascular diseases. With the prevalence of metabolic syndrome increasing rapidly and subsequently increasing burden on global health and welfare, optimizing treatment options is vital. This special issue on “Tailoring Biomaterials for Metabolic Diseases” is assembled to recognize recent progress in the use of biomaterials and associated formulations and devices toward this goal. This special issue consists of six original papers, three progress reports, and two review articles, contributed by world-leading researchers, mainly focusing on the treatment for diabetes along with obesity. Various biomaterials have emerged to address the problems caused by metabolic diseases and promote innovations in the drug delivery field. The progress report article from Farokhzad and co-workers (see article number 1801655) summarizes state-of-the-art delivery strategies including local, targeted, and oral drug delivery approaches, as well as intelligent stimulus-responsive methods, for the treatment of diabetes, obesity, and atherosclerosis. Also, a comprehensive introduction to the mechanism of obesity is given by Xu and co-workers (see article number 1801184) who review the design of nanomedicines, including a diversity of micro/nanoparticles and patches for the treatment of obesity and related comorbidities. Oral drug delivery, due to its good patient compliance and convenience of administration, is usually the primary choice in clinical treatments. However, to achieve desired treatment, the mucus and epithelial barriers have to be overcome. In a paper published by Gan and co-workers (see article number 1801123), protein corona liposome is used to enhance the oral bioavailability of insulin. In addition, insulin delivery through inhalation has been verified as an effective and well-tolerated route. Zhang and co-workers (see article number 1800910) report the use of insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) as an inhalation delivery system for type 2 diabetes treatment, which incorporates cytotoxicity evaluation and other acute toxicity tests. Glucose-responsive insulin delivery for improved glucose regulation with reduced risk of hypoglycemia is highly desirable for treating people with type 1 and advanced type 2 diabetes. A progress report summarized by Webber and co-workers (see article number 1801466) looks into the development of glucose-sensitive materials covering biomimetic protein-based systems and synthetic small molecule-mediated approaches. The translation perspectives regarding efficacy and safety are also discussed. Apart from insulin, glucagon-like peptide 1 (GLP-1) and GLP-1 analogs are clinically used peptide drugs that have weight loss effects, minimal risk of hypoglycemia, as well as prolonging the half-life in vivo. Chen and co-workers (see article number 1800686) develop long-lasting antidiabetic therapeutics, named Abextide, and evaluate its pharmacodynamics in nonhuman primates. This article highlights the antidiabetic potential of Abextide for weekly subcutaneous administration. Optimization of peptide drug delivery through molecular and materials engineering is summarized by Chilkoti and co-workers (see article number 1801509), which provides a thorough overview in addressing their limitations in clinical use such as instability and low efficacy in vivo. The replacement of destroyed beta cells offers an alternative approach to restore physiological glucose regulation and eliminate the need for exogenous insulin. However, these clinical islet transplantation therapies often suffer from poor durability of cellular function. Stabler and co-workers (see article number 1801493) seek out to coat encapsulated beta cells with a “nanoarmor” made of multi-layer cerium oxide nanoparticles to provide antioxidant protection. Another interconnected toroidal hydrogel-based device for islet encapsulation and β-cell replacement is presented by Ma and co-workers (see article number 1900423). The “donut-shape” with high surface area enables mass transport, while the interconnection and reversible deformation allow minimally invasive implantation as well as complete retrieval. In addition to exterior protection, maintaining the normal autophagic flux inside the pancreatic β-cells is critically important to keep the cellular functions running. In this case, lysosomal dysfunction caused by lipotoxicity may impair insulin secretion and lead to progressive diseases like type 2 diabetes. Grinstaff and co-workers (see article number 1801511) provide a new lysosomal acidification tool, poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which target and lower the lysosomal pH to rescue autophagic flux. Displaying a concentration dependent performance, PLGA nanoparticles can readily restore insulin secretion in pancreatic β-cells during its chronic exposure to high levels of fatty acids. Diabetes typified by dysregulation of blood glucose levels is more likely to form chronic wounds through complex pathophysiological mechanisms. Schoenfisch and co-workers (see article number 1801210) survey the advances in nitric oxide (NO)-based therapies for wound healing, specifically emphasizing the role of these therapies regarding diabetic wound healing. They cover the role of endogenous NO as well as means for generating exogenous NO in wound healing and chronic wound therapy. Overall, the publications presented in this special issue represent a diverse intersection of distinct biomaterials and methodologies that could be of great potential in designing the next generation of biomaterials for metabolic diseases. We hope these important endeavors will bridge fundamental studies with clinical needs to translate innovations for enhancing the health and quality of life of people with metabolic diseases. We would like to thank all authors who assisted us in organizing this special issue. We also greatly appreciate Dr. Bayindir-Buchhalter for her support throughout the process of creating this special issue. Zhen Gu is a professor of bioengineering at the University of California, Los Angeles (UCLA). He received his B.S. degree in chemistry and M.S. degree in polymer chemistry and physics from Nanjing University. In 2010, he obtained a Ph.D. degree from UCLA, under the guidance of Dr. Yi Tang from the Department of Chemical and Biomolecular Engineering. He was a postdoctoral associate working with Dr. Robert Langer at MIT and Harvard Medical School from 2010 to 2012. Before he moved to UCLA in 2018, he had been appointed as a Jackson Family Distinguished Professor in the Joint Department of Biomedical Engineering at the University of North Carolina at Chapel Hill and North Carolina State University. His group studies controlled drug delivery, bio-inspired materials, and nanobiotechnology, especially for cancer and diabetes treatment.