© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1 wileyonlinelibrary.com RESEARCH NEWS Living Cell Factories- Electrosprayed Microcapsules and Microcarriers for Minimally Invasive Delivery Syeda M. Naqvi, Srujana Vedicherla, Jennifer Gansau, Tom McIntyre, Michelle Doherty, and Conor T. Buckley* S. M. Naqvi, S. Vedicherla, J. Gansau, T. McIntyre, M. Doherty, Prof. C. T. Buckley Trinity Center for Bioengineering Trinity Biomedical Sciences Institute Trinity College Dublin, Ireland E-mail: conor.buckley@tcd.ie S. M. Naqvi, J. Gansau, C.T. Buckley Department of Mechanical Engineering School of Engineering Trinity College Dublin, Ireland S. Vedicherla, T. McIntyre School of Medicine Trinity College Dublin, Ireland DOI: 10.1002/adma.201503598 details, see review article. [2b] In the past few years, advances in the fields of biomate- rials and cell therapy, design of novel tissue engineering approaches and improve- ments in the fabrication of application tailored and advanced micro- and nano- carriers for protein and drug delivery have been some of the highlights. The progress in these areas has synergistically fueled the advances in the 60-year-old encapsula- tion technology opening new avenues of work. The ability to create “living cell fac- tories” by combining hydrogels and cells can now facilitate cell transplantation in a permeable system while isolating the cells from the host’s immune system has res- urrected the concept of allogeneic-based therapies. Such approaches eliminate the need for immunosuppression in allogenic cell delivery or toxicity in host cell expo- sure to drugs and more targeted delivery mechanisms. [3] Since the work of Biscglie in the early 30s who transplanted tumor cells enclosed in a polymer membrane into porcine abdominal cavity demonstrating cells were not destroyed by the immune system, [4] to successful practice of immobilizing xenograft islet cells to control diabetes in small animal models in the 70s and 80s, [5] advances have been rapid. At present there is an overwhelming resurrection in micro- particle fabrication technology with the design of biomimetic and biodegradable microcapsule and microcarrier systems which can be easily combined with cells and growth factors advancing the traditional tissue engineering model (Figure 1a and 1b). Direct needle injection of cells without biomaterial protection has the propensity to expose cells to excessive shear forces, risks cell leakage and elicit an undesired host-immune response. Encapsulation systems enhance the protection and transport of cells and drugs to targeted tissue sites, pro- mote cell integration and consequently tissue repair and regeneration. Microcapsule and microcarrier systems provide a larger sur- face area for cellular attachment, provide cell protection against excessive mechanical stresses and simulates an in vivo envi- ronment. [6] It also offers the advantage whereby these culture systems can be directly injectable biodegradable cell systems, allowing cell repopulation or augmentation of cell population through growth factor or drug release agents aimed at regenera- tion. With advanced fabrication techniques, various conformations of matrix core-shell, liquid core-shell, hollow core, coatings Minimally invasive delivery of living cell factoriesconsisting of cells and therapeutic agents has gained wide attention for next generation biomaterial device systems for multiple applications including musculoskeletal tissue regeneration, diabetes and cancer. Cellular-based microcapsules and microcarrier systems offer several attractive features for this particular purpose. One such technology capable of generating these types of systems is electrohydrodynamic (EHD) spraying. Depending on various parameters, including applied voltage, biomaterial properties (viscosity, conductivity) and needle geometry, complex structures and arrangements can be fabricated for therapeutic strategies. The advances in the use of EHD technology are outlined, specifically in the manipulation of bioactive and dynamic material systems to control size, composition and configuration in the development of minimally invasive micro-scaled biopolymeric systems. The exciting thera- peutic applications of this technology, future perspectives and associated challenges are also presented. 1. Introduction The arena of biomedical delivery systems has propagated in recent years following advances in polymeric materials science but also manufacturing technology, which has significantly enhanced biomedical therapeutics. Areas such as hormone and “short half-life” peptide delivery in diabetes, [1] regenerative ven- tures in cartilage, bone and neurodegenerative disorders [2] have all benefitted. The early advances in “living cell factories” have improved the pharmacokinetics and administration of drugs and consequently patient compliance and comfort (for further Adv. Mater. 2015, DOI: 10.1002/adma.201503598 www.advmat.de www.MaterialsViews.com