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    PublicationOpen Access
    3D printing of elastomeric bioinspired complex adhesive microstructures
    (Wiley, 2021) Dayan, Cem Balda; Chun, Sungwoo; Krishna Subbaiah, Nagaraj; Drotlef, Dirk Michael; Akolpoğlu, Mükrime Birgül; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104
    Bioinspired elastomeric structural adhesives can provide reversible and controllable adhesion on dry/wet and synthetic/biological surfaces for a broad range of commercial applications. Shape complexity and performance of the existing structural adhesives are limited by the used specific fabrication technique, such as molding. To overcome these limitations by proposing complex 3D microstructured adhesive designs, a 3D elastomeric microstructure fabrication approach is implemented using two-photon-polymerization-based 3D printing. A custom aliphatic urethane-acrylate-based elastomer is used as the 3D printing material. Two designs are demonstrated with two combined biological inspirations to show the advanced capabilities enabled by the proposed fabrication approach and custom elastomer. The first design focuses on springtail- and gecko-inspired hybrid microfiber adhesive, which has the multifunctionalities of side-surface liquid super-repellency, top-surface liquid super-repellency, and strong reversible adhesion features in a single fiber array. The second design primarily centers on octopus- and gecko-inspired hybrid adhesive, which exhibits the benefits of both octopus- and gecko-inspired microstructured adhesives for strong reversible adhesion on both wet and dry surfaces, such as skin. This fabrication approach could be used to produce many other 3D complex elastomeric structural adhesives for future real-world applications.
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    Publication
    A multinational Delphi consensus to end the COVID-19 public health threat
    (Nature Research, 2022) Lazarus, Jeffrey V.; Romero, Diana; Kopka, Christopher J.; Karim, Salim Abdool; Abu-Raddad, Laith J.; Almeida, Gisele; Baptista-Leite, Ricardo; Barocas, Joshua A.; Barreto, Mauricio L.; Bar-Yam, Yaneer; Bassat, Quique; Batista, Carolina; Bazilian, Morgan; Chiou, Shu-Ti; del Rio, Carlos; Dore, Gregory J.; Gao, George F.; Gostin, Lawrence O.; Hellard, Margaret; Jimenez, Jose L.; Kang, Gagandeep; Lee, Nancy; Matičič, Mojca; McKee, Martin; Nsanzimana, Sabin; Oliu-Barton, Miquel; Pradelski, Bary; Pyzik, Oksana; Rabin, Kenneth; Raina, Sunil; Rashid, Sabina Faiz; Rathe, Magdalena; Saenz, Rocio; Singh, Sudhvir; Trock-Hempler, Malene; Villapol, Sonia; Yap, Peiling; Binagwaho, Agnes; Kamarulzaman, Adeeba; El-Mohandes, Ayman; Barreto, Mauricio; del Rio, Carlos; Abdulla, Salim; Addleman, Sarah; Aghayeva, Gulnara; Agius, Raymond; Ahmed, Mohammed; Ramy, Mohamed Ahmed; Aide, Pedro; Aleman, Soo; Alfred, Jean-Patrick; Ali, Shamim; Aliaga, Jorge; Aloudat, Tammam; Alqahtani, Saleh A.; Al-Salman, Jameela; Amuasi, John H.; Agrawal, Anurag; Anwar, Wagida; Araujo-Jorge, Tania; Artaza, Osvaldo; Asadi, Leyla; Awuku, Yaw; Baker, Michael; Barberia, Lorena; Bascolo, Ernesto; Belcher, Paul; Bell, Lizett; Benzaken, Adele; Bergholtz, Emil; Bhadelia, Nahid; Bhan, Anant; Bilodeau, Stephane; Bitrán, Ricardo; Bluyssen, Philomena; Bosman, Arnold; Bozza, Fernando A.; Brinkmann, Melanie M.; Brown, Andrew; Mellado, Bruce; Bukusi, Elizabeth; Bullen, Chris; Buonanno, Giorgio; Burgess, Rochelle; Butler, Matthew; Byakika-Kibwika, Pauline; Cabieses, Baltica; Carlsson, Gunilla; Cascini, Fidelia; Chabala, Chishala; Chakroun, Mohamed; Cheng K.K.; Chetty, Agnes; Chumachenko, Dmytro; Consalves, Gregg; Conway Morris, Andrew; Cordie, Ahmed; Corrah, Tumani; Crabtree-Ramírez, Brenda; Dashdorj, Naranjargal; Davidovitch, Nadav; de Souza, Luis Eugenio; Dhariwal, Akshay Chand; Druică, Elena; Erondu, Ngozi A.; Essar, Mohammad Yasir; Ewing, Andrew; Fanjul, Gonzalo; Feierstein, Daniel; Feigl-Ding, Eric; Figueroa, Ramon; Figueroa, John Peter; Fisher, Dale; Flores, Walter; Forero-Peña, David A.; Frumkin, Howard; Gamkrelidze, Amiran; Gandhi, Monica; Garcia, Patricia; Garcia-Basteiro, Alberto L.; García-Sastre, Adolfo; Garg, Suneela; Gbeasor-Komlanvi F.A.; Gershenson, Carlos; Gilada, Ishwar; Giovanella, Ligia; González, Marino; Green, Manfred S.; Greenhalgh, Trisha; Griffin, Paul; Griffin, Stephen; Grinsztejn, Beatriz; Anand, Tanu; Guerra, Germán; Guinto, Renzo; Gujski, Mariusz; Guner, Rahmet; Hamdy, Adam; Hâncean, Marian-Gabriel; Haniffa, Abusayeed; Hartigan-Go, Kenneth Y.; Hassan, Hoda K.; Hay, Simon I.; Heino, Matti T. J.; Hel, Zdenek; Hotez, Peter; Hu, Jia; Hukić, Mirsada; IJsselmuiden, Carel; Iroko, Davidson; Iskarous, Maged; Izugbara, Chimaraoke; Jacobs, Choolwe; Jadad, Alejandro R.; Jehan, Fyezah; Jordan, Ayana; Jroundi, Imane; Kain, Kevin; Kamberi, Fatjona; Karamov, Eduard; Karan, Abraar; Katz, Rebecca; Katzourakis, Aris; Kazembe, Abigail; Khamis, Faryal; Khamzayev, Komiljon; Khanyola, Judy; Khunti, Kamlesh; Kiguli-Malwadde, Elsie; Kim, Woo Joo; Kirenga, Bruce J.; Klimovský, Daniel; Kmush, Brittany L.; Knaul, Felicia; Kogevinas, Manolis; Kristensen, Frederik; Kumar, Dinesh; Kumar, Raman; Kvalsvig, Amanda; Lacerda, Marcus V.; Lal, Arush; Lawton, Tom; Lemery, Jay; Leonardi, Anthony J.; Li, Yuguo; Löttvall, Jan; Lounis, Mohamed; Maceira, Daniel; MacIntyre, C. Raina; Madani, Azzeddine; Magiorkinis, Gkikas; Malekzadeh, Reza; Choisy, Marc; Marcelin, Jasmine R.; Marks, Guy B.; Marr, Linsey; Marrazzo, Jeanne; Martina, Antonieta; Martín-Moreno, José M.; Mateos, Carlos; Mayxay, Mayfong; Mazarati, Jean Bapiste; Mboup, Souleymane; McDonald, Jennifer; McMillan, Faye; Mechili, Enkeleint; Medici, Andre; Davis, Sarah L. M.; Meier, Petra; Memish, Ziad A.; Menon, Jaideep; Menon, Purnima; Mesiano-Crookston, Jonathan; Michie, Susan; Mikolasevic, Ivana; Milicevic, Ognjen; Mishra, Asit Kumar; Mohamed, Rahma; Mokdad, Ali H.; Monroy-Valle, Michele; Morawska, Lidia; Moschos, Sterghios A.; Motawea, Karam; Mousavi, Sayed Hamid; Mumtaz, Ghina; Munene, Peter K.; Muñoz Almagro, Carmen; Muriuki, Janet; Muyingo, Sylvia; Naniche, Denise; Naylor, C. David; Ndembi, Nicaise; Nemec, Juraj; Nesteruk, Igor; Ngaruiya, Christine; Nguyen, Hung; Nikolova, Dafina; Nitzan, Dorit; Norheim, Ole; Noushad, Mohammed; Ntoumi, Francine; Nyborg, Gunhild Alvik; Ochodo, Eleanor; Odabasi, Zekaver; Okwen, Mbah Patrick; Olivia, Keiser; Ong, David S. Y., Opara, Ijeoma; Orozco, Miguel; Oshitani, Hitoshi; Pagel, Christina; Pai, Madhukar; Pálsdóttir, Björg; Papatheodoridis, Georgios Paraskevis, Dimitrios; Leigh, Jeanna Parsons; Pécoul, Bernard; Peichl, Andreas; Perez-Then, Eddy; Duc, Phuc Pham; Philippe, Cécile; Pineda Rojas, Andrea; Pladsen, Courtney; Pozniak, Anton; Quiroga, Rodrigo; Qureshi, Huma; Rampal, Sanjay; Ranney, Megan; Rathe, Laura; Ratzan, Scott; Raventos, Henriette; Rees, Helen; Reis, Renata; Ricciardi, Walter; Rizk, Nesrine; Robalo, Magda; Robertson, Eleanor; Robinson, Leanne; Rokx, Casper; Ros, Tamsin; Røttingen, John-Arne; Rubin, Meir; Ruxrungtam, Kiat; Sadirova, Shakhlo; Saha, Senjuti; Salgado, Nelly; Sanchez, Lizet; Sangaramoorthy, Thurka; Santamaria-Ulloa, Carolina; Santos, Renata; Sawaf, Bisher; Schneider, Matthias F.; Schooley, Robert T.; Sener, Alper; Sepulveda, Jaime; Shah, Jaffer; Shibani, Mosa; Shoib, Sheikh; Sikazwe, Izukanji; Šimaitis, Aistis; Gill, Amandeep Singh; Skhvitaridze, Natia; Sokolović, Milka; Solomon, Roma; Solórzano, Xavier; Springer, Sandra A.; Šrol, Jakub; Staines, Anthony; Stelfox, Henry T.; Strathdee, Steffanie; Sulaiman, Lokman Hakim; Sutton, Brett; Svanæs, Dag; Swed, Sarya; Sypsa, Vana; Sørensen, Kristine; Tajudeen, Raji; Tan, Amy; Tang, Julian; Tanner, Marcel; Sethi, Tavpritesh; Temmerman, Marleen; Than, Kyu Kyu; Tinto, Halidou; Tomètissi, Sênoudé Pacôme; Torres, Irene; Tshering K.P.; Tsiodras, Sotirios; Tsofa, Benjamin; Vahlne, Anders; Vargas, Juan Rafael; Bernal, Ivan Dario Velez; Ventura, Deisy; Vilasanjuan, Rafael; Vipond, Joe; Wamala-Andersson, Sarah; Wargocki, Pawel; West, Robert; Weyand, Angela; White, Trenton M.; Wolff, Guntram; Yao, Maosheng; Yates, Christian A.; Yeboah, Georgina; Yee-Sin, Leo; Yi, Siyan; Teo, Yik-Ying; Yong, Poovorawan; Zamora-Mesía, Victor; Øvrehus, Anne; Ergönül, Önder; Faculty Member; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); School of Medicine; 110398
    Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.
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    PublicationOpen Access
    A tissue adhesion-controllable and biocompatible small-scale hydrogel adhesive robot
    (Wiley, 2022) Lee, Y.W.; Chun, S.; Son, D.; Hu, X.; Schneider, M.; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104
    Recently, the realization of minimally invasive medical interventions on targeted tissues using wireless small-scale medical robots has received an increasing attention. For effective implementation, such robots should have a strong adhesion capability to biological tissues and at the same time easy controlled detachment should be possible, which has been challenging. To address such issue, a small-scale soft robot with octopus-inspired hydrogel adhesive (OHA) is proposed. Hydrogels of different Young's moduli are adapted to achieve a biocompatible adhesive with strong wet adhesion by preventing the collapse of the octopus-inspired patterns during preloading. Introduction of poly(N-isopropylacrylamide) hydrogel for dome-like protuberance structure inside the sucker wall of polyethylene glycol diacrylate hydrogel provides a strong tissue attachment in underwater and at the same time enables easy detachment by temperature changes due to its temperature-dependent volume change property. It is finally demonstrated that the small-scale soft OHA robot can efficiently implement biomedical functions owing to strong adhesion and controllable detachment on biological tissues while operating inside the body. Such robots with repeatable tissue attachment and detachment possibility pave the way for future wireless soft miniature robots with minimally invasive medical interventions.
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    PublicationOpen Access
    An integrated computational-experimental hierarchical approach for the rational design of an IL/UiO-66 composite offering infinite CO2 selectivity
    (Wiley, 2022) Department of Chemical and Biological Engineering; Department of Chemistry; Zeeshan, Muhammad; Gülbalkan, Hasan Can; Durak, Özce; Haşlak, Zeynep Pınar; Ünal, Uğur; Keskin, Seda; Uzun, Alper; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Chemistry; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; N/A; N/A; N/A; 42079; 40548; 59917
    Owing to the possibility of generating theoretically unlimited numbers of ionic liquid (IL)-metal-organic framework (MOF) combinations, experimental studies on IL/MOF composites for gas separation applications are mostly conducted on a trial-and-error basis. To address this problem, an integrated computational-experimental hierarchical approach is presented for selecting the best IL-MOF combination for a target gas separation application. For this purpose, UiO-66 and pyrrolidinium-based ILs are chosen as the parent MOF and IL family, respectively, and three powerful computational tools, Conductor-like Screening Model for Realistic Solvents calculations, density functional theory calculations, and grand canonical Monte Carlo simulations, are integrated to identify the most promising IL-UiO-66 combination as 1-n-butyl-1-methylpyrrolidinium dicyanamide/UiO-66, [BMPyrr][DCA]/UiO-66. Then, this composite is synthesized, characterized in deep detail, and tested for CO2/N-2, CO2/CH4, and CH4/N-2 separations. Results demonstrate that [BMPyrr][DCA]/UiO-66 offers an extraordinary gas separation performance, with practically infinite CO2 and CH4 selectivities over N-2 at 15 degrees C and at low pressures. The integrated hierarchical approach proposed in this work paves the way for the rational design and development of novel IL/MOF composites offering exceptional performance for any desired gas separation application.
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    PublicationOpen Access
    Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication
    (Nature Portfolio, 2021) Yurtman, Erinç; Özer, Onur; Yüncü, Eren; Dağtaş, Nihan Dilşad; Koptekin, Dilek; Çakan, Yasin Gökhan; Özkan, Mustafa; Akbaba, Ali; Kaptan, Damla; Atağ, Gözde; Vural, Kıvılcım Başak; Gündem, Can Yümni; Martin, Louise; Kılınç, Gülşah Merve; Ghalichi, Ayshin; Açan, Sinan Can; Yaka, Reyhan; Sağlıcan, Ekin; Lagerholm, Vendela Kempe; Krzewinska, Maja; Gunther, Torsten; Miranda, Pedro Morell; Pişkin, Evangelia; Sevketoğlu, Müge; Bilgin, C. Can; Atakuman, Ciğdem; Erdal, Yılmaz Selim; Sürer, Elif; Altınışık, N. Ezgi; Lenstra, Johannes A.; Yorulmaz, Sevgi; Abazari, Mohammad Foad; Hoseinzadeh, Javad; Baird, Douglas; Bıcakcı, Erhan; Çevik, Özlem; Gerritsen, Fokke; Gotherstrom, Anders; Somel, Mehmet; Togan, İnci; Özer, Füsun; Department of Archeology and History of Art; Özbal, Rana; Faculty Member; Department of Archeology and History of Art; College of Social Sciences and Humanities; 55583
    Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.
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    PublicationOpen Access
    Bio-inspired robotic collectives
    (Nature Publishing Group (NPG), 2019) Department of Electrical and Electronics Engineering; Sitti, Metin; Faculty Member; Department of Electrical and Electronics Engineering; School of Medicine; College of Engineering
    A robotic system has been demonstrated in which the random motion of individual components leads to deterministic behaviour, much as occurs in living systems. Environmental and medical applications could follow.
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    PublicationOpen Access
    Bioabsorbable polymer optical waveguides for deep-tissue photomedicine
    (Nature Publishing Group (NPG), 2016) Gather, Malte C.; Humar, Matjaz; Choi, Myunghwan; Kim, Seonghoon; Kim, Ki Su; Hahn, Sei Kwang; Scarcelli, Giuliano; Randolph, Mark; Redmond, Robert W.; Yun, Seok Hyun.; Department of Electrical and Electronics Engineering; Nizamoğlu, Sedat; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; 130295
    Advances in photonics have stimulated significant progress in medicine, with many techniques now in routine clinical use. However, the finite depth of light penetration in tissue is a serious constraint to clinical utility. Here we show implantable light-delivery devices made of bio-derived or biocompatible, and biodegradable polymers. In contrast to conventional optical fibres, which must be removed from the body soon after use, the biodegradable and biocompatible waveguides may be used for long-term light delivery and need not be removed as they are gradually resorbed by the tissue. As proof of concept, we demonstrate this paradigm-shifting approach for photochemical tissue bonding (PTB). Using comb-shaped planar waveguides, we achieve a full thickness ( 410 mm) wound closure of porcine skin, which represents similar to 10-fold extension of the tissue area achieved with conventional PTB. The results point to a new direction in photomedicine for using light in deep tissues.
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    PublicationOpen Access
    Biocompatible quantum funnels for neural photostimulation
    (American Chemical Society (ACS), 2019) N/A; Department of Chemical and Biological Engineering; N/A; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; N/A; Jalali, Houman Bahmani; Doğru-Yüksel, Itır Bakış; Eren, Güncem Özgün; Nizamoğlu, Sedat; Karatüm, Onuralp; Melikov, Rustamzhon; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; Sadeghi, Sadra; Yıldız, Erdost; Ergün, Çağla; Şahin, Afsun; PhD Student; Faculty Member; PhD Student; Master Student; Faculty Member; PhD Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; School of Medicine; N/A; N/A; N/A; 130295; N/A; N/A; N/A; 40319; N/A; N/A; N/A; 171267
    Neural photostimulation has high potential to understand the working principles of complex neural networks and develop novel therapeutic methods for neurological disorders. A key issue in the light-induced cell stimulation is the efficient conversion of light to bioelectrical stimuli. In photosynthetic systems developed in millions of years by nature, the absorbed energy by the photoabsorbers is transported via nonradiative energy transfer to the reaction centers. Inspired by these systems, neural interfaces based on biocompatible quantum funnels are developed that direct the photogenerated charge carriers toward the bionanojunction for effective photostimulation. Funnels are constructed with indium-based rainbow quantum dots that are assembled in a graded energy profile. Implementation of a quantum funnel enhances the generated photoelectrochemical current 215% per unit absorbance in comparison with ungraded energy profile in a wireless and free-standing mode and facilitates optical neuromodulation of a single cell. This study indicates that the control of charge transport at nanoscale can lead to unconventional and effective neural interfaces.
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    PublicationOpen Access
    Biodegradable untethered magnetic hydrogel milli-grippers
    (Wiley, 2020) Goudu, Sandhya Rani; Yasa, İmmihan Ceren; Hu, Xinghao; Ceylan, Hakan; Hu, Wenqi; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104
    Small-scale magnetic soft-bodied robots based on biocompatible and biodegradable materials are essential for their potential high-impact minimally invasive medical applications inside the human body. Therefore, a strategy for fully biodegradable untethered soft millirobots with encoded 3D magnetic anisotropy for their static or dynamic shape programming is presented. Such a robot body is comprised of a porcine extracellular matrix-derived collagen-based hydrogel network with embedded superparamagnetic iron oxide nanoparticles (SPIONs). 3D magnetization programming inside the hydrogel body is achieved by directionally self-assembled SPION chains using an external permanent magnet. As a proof-of-concept demonstration, a hydrogel milli-gripper that can undergo flexible and reversible shape deformations inside glycerol and biologically relevant liquid media is presented. The gripper can perform cargo grabbing, transportation by rolling, and release by controlling magnetic field inputs. These milli-grippers can be completely degraded by the matrix metalloproteinase-2 enzyme in physiologically relevant concentrations. Furthermore, biocompatibility tests using human umbilical cord vein endothelial cells with the degradation products of the grippers demonstrate no acute toxicity. The approach offers a facile fabrication strategy for designing biocompatible and biodegradable soft robots using nanocomposite materials with programmable 3D magnetic anisotropy toward future medical applications.
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    PublicationOpen Access
    Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology
    (Nature Portfolio, 2021) de la Pena, Osuna D.; Trabulo, S.M.D.; Collin, E.; Liu, Y.; Sharma, S.; Tatari, M., Behrens, D.; Lawlor, R.T.; Scarpa, A.; Heeschen, C.; Mata, A.; Loessner, D.; Erkan, Murat Mert; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 214689
    Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches.