Low-cost, Roll-to-Roll Manufacturing of Nanoscale Biomimetic Scaffolds for Enhanced Biological Cell Culture

PROJECT SUMMARY Cell culture technology is at the heart of all fundamental cell biology researchDisease modelingstem cell researchdrug developmentand tissue engineering all rely heavily on the in vitro culture of cellsCells isolated or grown in the laboratory are oftentimes maintained in cell culture vessels made of glass or plasticThese vessels lack the structuralmechanicaland chemical microenvironmental cues that cells use to regulate processes as diverse as cell signalingdifferentiationdivisionand even life and deathThese cues originate from the extracellular matrixECMwhich exhibits a range of essential chemical and mechanical properties that vary widely from organ to organThe failure of traditional cultureware to reproduce these vital ECM cues is a significant contributor to the non physiologic structuralphenotypicand functional development of in vitro cell culturesimpairing the predictive in vitro assessment of cellular responses to drugs and pathological challengeResearchers employ a variety of approaches to enhance the physiologic relevance of in vitro cell culture environments toward platforms that better resemble native cellular nichesMany of these techniques are a challenge to implementthey require expensive fabrication equipment and manual labor and demand a trade off between scalability and biological complexityFurtherthese approaches can suffer from significant failure rates and poor reproducibilityCustomizing the structural and mechanical properties of cell culture niches is timeconsumingmaking it a challenge to adapt these culture niches to new model systemsNanoSurface Biomedical proposes to develop a platform based on roll to roll nano imprint lithographyR RNILcapable of fabricating customizable culture substrates with biomimetic nanoscale topographies at scaleWhile R RNIL has been used extensively in the nanoelectronics industryit has not yet been adapted to manufacturing processes for cell biology applicationsOver the course of this projectthe company will design and fabricate a custom productionready R RNIL machine with components tailored to the production of biocompatible substrates with biomimetic microenvironmental architecturesThis novel R RNIL platform will offer facile adjustment of the shapeorientationand mechanical properties of the printed substrate materialThrough these effortsthe company will produce a first and only platform for the high throughput fabrication of nanoscale biomimetic cell culture niches that can be easily adapted to a variety of applicationsCulture niches that recapitulate the shape and structure of the extracellular environment of heart and bone tissue will be fabricatedCells grown on these substrates are expected to show phenotypes that are more representative of human physiologyincreasing the predictive power of many cell based assaysThis work will serve as the basis for progression into Phasewhere a wider variety of cell culture niches and novel tunable substrates will be developed PROJECT NARRATIVE We will develop a new roll to roll nano imprint lithography platform to fabricate biomimetic cell culture substrates at low cost and production scaleThe platform will allow for rapidfacileand cost effective adjustment of the nanoscale shape and mechanical properties of the substrates in order to better reproduce critical extracellular cues that regulate cell development and functionThis platform has great potential to enhance the predictive power of many cell based assays by inducing phenotypes that are more representative of human physiology