Biomaterials Research at the Georgia Institute of Technology

As the chairman of the Editorial Advisory Board, it is my great pleasure to organize this special issue to celebrate the 10th anniversary of Advanced Healthcare Materials (AHM), an international journal with a mission to report cutting-edge research in advanced materials, devices, and technologies which have a major impact on human health. Over the past 10 years, AHM has published more than 2500 manuscripts from over 60 countries in diverse areas of biomaterials, biointerfaces, biofabrication, tissue engineering, nanomedicine, regenerative medicine, and diagnostic devices for healthcare. This special issue includes contributions from research groups that are affiliated with the Wallace H. Coulter Department of Biomedical Engineering (BME) at the Georgia Institute of Technology (Georgia Tech) and Emory University, together with three from the School of Chemical & Biomolecular Engineering and three from the School of Mechanical Engineering, both at Georgia Tech. Founded in 1995, the BME program is a unique partnership between Georgia Tech and Emory University. Separated by a driving distance of only 5.5 miles (8.9 km), both institutions are located in Atlanta, GA, with the former known for its leading public engineering school and the latter for a highly respected private medical school. With 1161 currently enrolled undergraduates and 239 currently enrolled graduate students, the undergraduate and graduate programs are both ranked #2 by the U.S. News and World Report. The 68 BME faculty members are working on a large number of research focus areas, including biomaterials and regenerative technologies, biomedical imaging and instrumentation, biomedical informatics and systems modeling, biomedical robotics, cancer technologies, cardiovascular engineering, engineering education, immunoengineering, and neuroengineering. As limited by the scope of this journal, here we can only highlight the cutting-edge research in some of these areas, with a focus on biomaterials. The articles are broadly grouped into five categories: nanomedicine, biofabrication, immunoengineering, regenerative medicine, and tool/method development. In the context of nanomedicine (a.k.a. controlled release, drug delivery, and/or vaccine), James Dahlman and co-workers review recent progress in the development of RNA therapeutics for COVID-19 and other diseases (2002022). RNA can alter the expression of endogenous genes and thereby therapeutic proteins, but it has been a grand challenge to deliver therapeutic quantities of RNA-based drugs into the diseased cells. Specifically, they discuss how the biological hurdles that make in vivo delivery challenging can be overcome in humans by focusing on siRNA to treat liver disease and mRNA to vaccinate against COVID-19. In another review (2002031), myself and co-workers highlight our own efforts in radiolabeling gold nanocages for potential use in image-guided cancer therapy. Enabled by their hollow interior, porous wall, and tunable optical absorption in the near-infrared region, gold nanocages have emerged as a multifunctional platform for nanomedicine, including controlled release, drug delivery, imaging, diagnosis, and therapy. Labeling them with radionuclides for position emission tomography (PET) offers additional therapeutic capabilities while making it easier to analyze their biodistribution, monitor their uptake by the tissue or organ of interest, and optimize their performance in cancer theranostics. In a research article (2001894), Hanjoong Jo and co-workers report the bioconjugation of poly(β-amino ester) (pBAE) nanoparticles with VHPK peptides to target vascular cell adhesion molecule 1 for the delivery of RNA interference drugs. Specifically, the VHPK-conjugated pBAE nanoparticles are effective in delivering anti-microRNA-712 into inflamed endothelial cells both in vitro and in vivo, reducing the expression of pro-atherogenic microRNA-712. In another research article (2001810), Julie A. Champion and co-workers report the self-assembly of thermo-responsive, elastin-like polypeptide fusion protein and fluorescent fusion protein for the fabrication of photo-crosslinked protein vesicles. The size and swelling behavior of the resultant protein vesicles can be tailored by varying the hydrophobicity of the protein and the ionic strength. The vesicles are further explored for the dual delivery of doxorubicin and fluorescent protein in vitro. Related to biofabrication, Vahid Serpooshan, Steven A. Sloan, and their co-workers discuss how bioprinting can be adapted to better model the formation, function, and repair of the human nervous system by enabling a precise control over in vitro culture conditions (2001600). They specifically focus on the use of bioprinted in vitro platforms for developmental and disease modeling and drug screening applications within the central and peripheral nervous systems, in addition to their niche as implants for in vivo regenerative therapies. Yonggang Ke and co-workers review the key concepts and recent advancement in utilizing DNA nanostructures (also widely known as origamis) to develop biosensors and therapeutics (2002205). Powered by their intrinsic biocompatibility, precision in terms of functionalization, and programmability, the DNA-based nanostructures provide a unique platform for manipulating small molecules, nucleic acids, proteins, viruses, and cancer cells. In a research article (2001169), Vahid Serpooshan and co-workers report the use of 3D bioprinting and perfusion bioreactor technologies to fabricate bioartificial constructs that can serve as high-fidelity models of the developing human heart. As a major advantage, this platform allows for the study of normal developmental processes and underlying diseases by offering a precise control of the microenvironmental factors, including flow and geometry. In the framework of immunoengineering, Gabriel A. Kwong and co-workers review recent progress in interfacing biomaterials with synthetic T cell immunity (2100157). Specifically, they concentrate on three frontiers, including low-cost cell manufacturing to broaden patient access, noninvasive diagnostics for predictive monitoring of immune responses, and strategies for in vivo control and thus enhancement in anti-tumor immunity. They also discuss some of the challenges associated with T cell immunotherapy and how to address these challenges by engineering biomaterials to better interface with synthetic immunity. Erik C. Dreaden and co-workers review recent progress in cytokine engineering, with an emphasis on the early-stage therapeutic approaches (2002214). Cytokine signaling plays a critical role in a range of biological processes, including cell development, tissue repair, aging, and immunity. Specifically, they discuss a myriad of strategies that may be employed to improve the therapeutic potential of cytokine and chemokine immunotherapies with implications for cancer and autoimmune disease therapy, as well as tissue engineering and regenerative medicine. These strategies are presented according to their size scales, including single amino acid substitutions, protein-polymer conjugates, nano/micrometer particles, and macroscale implants. In a research article (2001947), Todd A. Sulchek and co-workers demonstrate the use of heterofunctional particles as single cell sensors to capture secreted immunoglobulins and isolate antigen-specific plasma cells. They challenge hybridoma cells with particles of two different designs, Janus and mixed. Janus particles are found to bind the target cells more effectively while mixed particles lead to improvement in antibody collection. The heterofunctional particles are also employed to capture antibody secreting cells that produce antibodies specific for influenza virus from the B cells isolated from the blood of healthy adults after vaccination. In another research article (2001899), Krishnendu Roy and co-workers evaluate how soluble and biomaterial-mediated delivery of Toll-like receptor (TLR)-targeted adjuvants modulate 3D chemotaxis of bone marrow-derived dendritic cells (BMDCs) toward lymphatic chemokine gradients. In order to induce CCR7 expression and chemotaxis of BMDCs, it is critical to supplement the granulocyte-macrophage colony stimulating factor-derived BMDC culture with interleukin-4. The results indicate both adjuvant type and delivery method influence chemotaxis of BMDCs, pointing toward a new direction for the rational design of vaccine formulations. In a third research article (2002140), Ravi S. Kane and co-workers report the use of nanopatterning in refocusing the immune response to selected epitopes on a Zika virus protein antigen. They designed two different nanopatterned DIII variants and further demonstrate that epitope shielding with PEG completely inhibits the binding of epitope-specific antibodies in vitro. In addition, immunization with multivalent nanopatterned DIII antigens leads to the refocusing of the antibody response toward the exposed epitopes on the protein surface and away from potentially enhancing epitopes. Related to regenerative medicine, Johnna Temenoff and co-workers review the effects of culture and material properties on the proliferation and surface marker expression of mesenchymal stromal cells (MSCs), as well as commonly used indications for therapeutic potency (2100016). Specifically, they examine the use of alternative culture formats such as cellular aggregates and 3D scaffolds, in addition to the effects of culture substrate stiffness and presentation of specific adhesive ligands and topographical cues. They further assess specific substrate properties that can be optimized to enhance cell expansion and improve specific therapeutic functionalities, demonstrating the use of culture materials in augmenting the clinical-scale manufacture of highly secretory MSC products. In another review article (2002285), YongTae Kim and co-workers review recent progress in developing an on-a-chip platform for Alzheimer's disease (AD) studies, with a focus on the blood–brain barrier (BBB): a unique vascular structure that serves as a molecular transport gateway for the maintenance of brain homeostasis. Specifically, they highlight recent progress in the development of human BBB-on-a-chip technologies, together with their potential use in pathogenesis studies and drug prescreening for AD treatment. In a third review article (2100115), Lakshimi Prasad Dasi and co-workers discuss the clinical potential of transcatheter heart valves (THVs) from a biomaterial perspective. Transcatheter heart valve replacement (THVR) offers a safe and minimally invasive procedure for high-risk patients. Specifically, the authors present a detailed account of the materials development for THVRs, including how the materials are selected, fabricated, prepared, and assembled into THVs, followed by a discussion of current and future THVR biomaterial trends. As for tool/method development, Cheng Zhu and co-workers review recent progress in the field of neuromechnobiology (2100102). With a focus on several neuronal processes, the authors specifically discuss how forces affect ligand binding, conformational change, and signal induction of molecules, especially at the synapse. They also examine the disease relevance of neuromechanobiology, together with therapies and engineering solutions to neurological disorders related to this emergent field of study. In a research article (2001887), Hang Lu and co-workers report a simple and yet effective technique, termed “microswimmer combing,” for rapidly isolating live small animals on an open-surface array. This technique relies on the use of a dynamic contact line-combing mechanism to handle highly active microswimmers. The open-surface device holds promises for multiple screening applications, including high-resolution imaging of multicellular organisms, on-demand mutant selection, and multiplexed chemical screening. It is expected to find use in investigating fundamental biology and drug development. In another research article (2100879), Shuichi Takayama and co-workers report a new method enabled by density-driven underside epithelium seeding for the fabrication of high-throughput distal lung air-blood barrier model. The immediate product is a 96-well model of the small airway-vascular barrier complete with serum-free, glucocorticoid-free air-liquid differentiation. The seeding method should be extendible to the preparation of various types of co-culture tissue barrier models for scalable, physiologic screening. The intention of this special issue is to provide the readers some snapshots of biomaterials research conducted by the faculty at Georgia Tech. Unfortunately, a number of invited manuscripts were unable to make it into this special issue due to the interruption caused by the outbreak of COVID-19. Nevertheless, it is hoped that the readers will still enjoy the diversity of topics covered by the articles included in this issue, and more importantly, find the inspiration to join me and my colleagues in developing advanced biomaterials for healthcare and related applications. Younan Xia studied at the University of Science and Technology of China (B.S., 1987) and University of Pennsylvania (M.S., 1993) before receiving his Ph.D. from Harvard University in 1996 (with George M. Whitesides). He started as an assistant professor of chemistry at the University of Washington (Seattle) in 1997 and was promoted to associate professor and professor in 2002 and 2004, respectively. He joined the Department of Biomedical Engineering at Washington University in St. Louis in 2007 as the James M. McKelvey Professor. Since 2012, he holds the position of Brock Family Chair and GRA Eminent Scholar in Nanomedicine at the Georgia Institute of Technology.