OBJECTIVES/GOALS: Use an easily accessible medium to educate life science researchers and academic innovators interested in the commercialization of academic research at the University of Michigan (UM). METHODS/STUDY POPULATION: Life science research investigators and academic innovators interested in research commercialization and technology development from across the state of Michigan were invited to attend the Idea to Impact: The Translation & Commercialization of Academic Research webinar series, presented by Fast Forward Medical Innovation at the University of Michigan. The webinar series outlined the significance and critical milestones of developing novel therapeutics, medical devices, diagnostics, and digital health innovations, as well as essential collaborations with industry partners to translate a research-based idea into a product of impact. RESULTS/ANTICIPATED RESULTS: 113 investigators and innovators from 28 different institutions, organizations, and companies, registered for the webinar series. Results (N=24) of an evaluation immediately following each webinar revealed that 100% of respondents strongly agreed or agreed that the series was effective in helping them to identify and describe commercialization resources, including funding, education, and mentorship, available at the University of Michigan and within the state. Participants stated that they “loved the practical information” “shared” and that the series was a “great overview that inspired a lot more questions.” The Fast Forward Medical Innovation team was then able to consult with participants to connect them with additional resources. DISCUSSION/SIGNIFICANCE: The data suggests that easily accessible and digestible commercialization education can make navigating the academic entrepreneurial ecosystem easier for investigators and innovators. The recorded webinar series, Idea to Impact: The Translation & Commercialization of Academic Research, serves this purpose.

OBJECTIVES/GOALS: The University of Michigan Frankel Cardiovascular Center (FCVC) Innovation Challenge is an annual competition offering funding for innovative ideas to improve cardiovascular care. Due to the COVID-19 pandemic, administrators converted the recruitment process and pitch event to fully virtual. METHODS/STUDY POPULATION: We detail the process of converting the event from a hybrid process (virtual and in-person recruiting and in-person event) to a fully virtual one. Changes to the event included implementing a virtual recruiting process utilizing short video recordings as submission format; a new tool for storing and displaying submissions; fully virtual finalist selection and coaching; and a fully virtual pitch and judging event. The submission process tracked information about submissions that include the type of idea (process or product), role of team lead, and department of team lead. RESULTS/ANTICIPATED RESULTS: The FCVC Innovation Challenge was successfully converted to a fully virtual event. Methods and tools will be shared to allow similar institutions to replicate a successful virtual pitch event. These include methods and tools utilized to allow participants to describe their ideas, strategies to select and coach finalists, and to host a virtual pitch event. Data will be shared on the number of ideas and category (product/process) of projects submitted, and number and category of finalists selected. DISCUSSION/SIGNIFICANCE: This case review can demonstrate how institutions can use a similar virtual idea submission and pitch process to (1) catalyze innovative ideas that can impact patient care by accessing its communitys ideas and (2) fund innovative ideas that do not fit traditional mechanisms.

Traditional training and funding mechanisms in academic health centers often do not support its faculty, staff, and trainees in evaluating and implementing innovative ideas, necessitating supplemental innovation programming. The University of Michigan (U-M) Frankel Cardiovascular Center partnered with U-M Fast Forward Medical Innovation (FMMI), a biomedical innovation and commercialization unit funded in part by the Clinical and Translational Science Award awarded to the Michigan Institute for Clinical & Health Research, to provide training and resources to advance ideas toward impacting patients. The program recruited faculty, trainees, staff, patients, and family members from multidisciplinary backgrounds. Engaging patients and family members expanded the ideas generated and furthered clinical relevance. Over two years, 11 project teams completed an 11-week, 16-session course on innovation and entrepreneurship concepts that incorporated workshops to progress ideas and develop a pitch for development funding. An increase in knowledge was reported in key innovation topics, such as customer discovery, assessing markets, and intellectual property. Participants reported an increase in project preparation, including obtaining stakeholder support, preparation of a development plan, readiness to apply for funding, and filing invention disclosures. This program can serve as a model for implementing training and funding mechanisms to advance innovative ideas.

Healthcare providers are expected to deliver care improvement solutions that not only provide high quality patient care, but also improve outcomes, reduce costs, ensure safety, and increase patient satisfaction. Human-centered design methodologies, such as design thinking, allow providers to collaboratively ideate solutions with patients and family members. We describe a pilot workshop designed to teach providers the stages of design thinking while working on improving patient-provider communication. Twenty-four providers (physicians, nurses, technical staff, and administrative staff) from multiple cardiovascular units attended the workshop with five former patients and family members from those units. The workshop educated on and guided teams of providers patients and family members through the stages of design thinking (empathy, define, ideate, prototype, test). Pre- and post-event assessments indicated an increase in knowledge of the design thinking methodology and participants' ability to apply it to a clinical problem. We also present recommendations for designing a successful design thinking workshop.

Replication of bone marrow niches is essential for the evaluation of the toxicity and efficacy of multiple drug candidates and understanding of cell development. Recreation of the complex biological environment of bone marrow in a suitable format for such studies can be accomplished using bone-mimetic constructs based on three-dimensional (3D) nanocomposite-coated cell scaffolds with inverted colloidal crystal geometry. Layer-by-layer (LBL) assembled nanocomposites combine the mechanical properties and surface topography of bone with the transparency of 3D cell matrices. Such rare combination of properties allows for discrimination and control of complex biological processes such as differentiation of bone marrow stromal cells. LBL biomimetic nanocomposites open the pathway toward better understanding of the interactions between stromal cells and the extracellular matrix in the bone marrow microenvironment, in order to achieve the accurate engineering of the bone marrow niches.

3D Biomatrix, LLC www.3DBiomatrix.com.... support@3DBiomatrix.com...(734).27284688. 1600.Huron.Parkway,.Building.520,.2nd.Floor,.Ann.Arbor,.MI.48109,.USA. Corresponding.Author:. Professor Shuichi Takayama takayama@umich.edu. Biomedical.Engineering,.University.of.Michigan. Mixed Co-Culture Spheroids. PC83DsRed.human.prostate.cancer.. cells,.human.embilical.vein.endothelial.(HUVEC).cells,.and.MC3T38E1. mouse.preosteoblast.cells.were.seeded.together.to.form.mixed.co8culture. spheroids..PC83DsRed.cells.are.randomly.distributed.within.the.spheroid..

The comparative evaluation of different 3D matrices-Matrigel, Puramatrix, and inverted colloidal crystal (ICC) scaffolds-provides a perspective for studying the pathology and potential cures for many blood and bone marrow diseases, and further proves the significance of 3D cultures with direct cell-cell contacts for in vitro mimicry of the human stem cell niche.

We report the construction of novel temperature-responsive assemblies based on a double hydrophilic block copolymer (consisting of a PEG block and a β-cyclodextrin-containing block, PEG-b-PCD) and poly(N-isopropylacrylamide) (PNIPAm). Thus formed nano-assemblies exhibit a spherical morphology and have a temperature-responsive loose core. The driving force for the formation of these assemblies was found to be the inclusion complexation interaction between the hydrophobic cavity of β-cyclodextrin and the isopropyl group of PNIPAm. The particle size of these assemblies changed reversibly in response to the external temperature change. The particle size also changed with the PNIPAm/PEG-b-PCD weight ratio. A model hydrophobic drug (indomethacin) was loaded into these assemblies with a high efficiency. An in vitro release study showed that the payload could be released in a sustained manner after an initial burst release. The release rate could be switched between high and low in an On/Off fashion by temperature. These results demonstrate that the nano-assemblies have high potential for applications in controlled drug delivery and biomedicine when temperature responsiveness is desired.

Multicellular spheroids provide a new three-dimensional (3D) level of control over morphology and function of ex vivo cultured tissues. They also represent a valuable experimental technique for drug discovery and cell biology. Nevertheless, the dependence of many cellular processes on the cluster diameter remains unclear. To provide a tool for the systematic evaluation of such dependences, we introduce here inverted colloidal crystal (ICC) scaffolds. Uniformly sized pores in ICC cell matrixes afford a high yield production of controlled size spheroids in standard 96 well-plates. Transparent hydrogel matrix and ship-in-bottle effect also allows for convenient monitoring of cell processes by traditional optical techniques. Different developmental stages of 46.5-151.6 microm spheroids from HepG2 hepatocytes with vivid morphological similarities to liver tissue (bile canaliculi) were observed. The liver-specific functions of HepG2 cells were systematically investigated and compared for spheroids of different diameters as well as 2D cultures. Clear trends of albumin production and CYP450 activity were observed; diffusion processes and effect of cellular aggregation on metabolic activity were identified to be the primary contributors to the size dependence of the liver functions in HepG2 spheroids in ICC scaffolds. Since the aggregation of cells into clusters is a universal biological process, these findings and scaffolds can be applied to many other relevant cell types.

Multilayered thin films prepared with the layer-by-layer (LBL) assembly technique are typically "brittle" composites, while many applications such as flexible electronics or biomedical devices would greatly benefit from ductile, and tough nanostructured coatings. Here we present the preparation of highly ductile multilayered films via LBL assembly of oppositely charged polyurethanes. Free-standing films were found to be robust, strong, and tough with ultimate strains as high as 680% and toughness of approximately 30 MJ/m(3). These results are at least 2 orders of magnitude greater than most LBL materials presented until today. In addition to enhanced ductility, the films showed first-order biocompatibility with animal and human cells. Multilayered structures incorporating polyurethanes open up a new research avenue into the preparation of multifunctional nanostructured films with great potential in biomedical applications.

Recent advances and progress in nanobiotechnology have demonstrated many nanoparticles (NPs) as potential and novel drug delivery vehicles, therapeutic agents, and contrast agents and luminescent biological labels for bioimaging. The emergence of new biomedical applications based on NPs signifies the need to understand, compare, and manage their cytotoxicity. In this study, we demonstrated the use of high-content screening assay (HCA) as a universal tool to probe the cytotoxicity of NPs and specifically cadmium telluride quantum dots (CdTe QDs) and gold NPs (Au NPs) in NG108-15 murine neuroblastoma cells and HepG2 human hepatocellular carcinoma cells. Neural cells represent special interest for NP-induced cytotoxicity because the optical and electrical functionalities of materials necessary for neural imaging and interfacing are matched well with the properties of many NPs. In addition, the cellular morphology of neurons is particularly suitable for automated high content screening. HepG2 cells represent a good model for high content screening studies since they are commonly used as a surrogate for human hepatocytes in pharmaceutical studies. We found the CdTe QDs to induce primarily apoptotic response in a time- and dosage-dependent manner and produce different toxicological profiles and responses in undifferentiated and differentiated neural cells. Au NPs were found to inhibit the proliferation and intracellular calcium release of HepG2 cells.

Traditional methods of cell growth and manipulation on 2-dimensional (2D) surfaces have been shown to be insufficient for new challenges of cell biology and biochemistry, as well as in pharmaceutical assays. Advances in materials chemistry, materials fabrication and processing technologies, and developmental biology have led to the design of 3D cell culture matrices that better represent the geometry, chemistry, and signaling environment of natural extracellular matrix. In this review, we present the status of state-of-the-art 3D cell-growth techniques and scaffolds and analyze them from the perspective of materials properties, manufacturing, and functionality. Particular emphasis was placed on tissue engineering and in vitro modeling of human organs, where we see exceptionally strong potential for 3D scaffolds and cell-growth methods. We also outline key challenges in this field and most likely directions for future development of 3D cell culture over the period of 5-10 years.

Controllability of scaffold architecture is essential to meet specific criteria for bone tissue engineering implants, including adequate porosity, interconnectivity, and mechanical properties to promote bone growth. Many current scaffold manufacturing techniques induce random porosity in bulk materials, requiring high porosities (>95%) to guarantee complete interconnectivity, but the high porosity sacrifices mechanical properties. Additionally, the stochastic arrangement of pores causes scaffold-to-scaffold variation. Here, we introduce a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold with an inverted colloidal crystal (ICC) structure that provides a highly ordered arrangement of identical spherical cavities. Colloidal crystals (CCs) were constructed with soda lime beads of 100-, 200-, and 330-mum diameters. After the CCs were annealed, they were infiltrated with 85:15 PLGA. The method of construction and highly ordered structure allowed for ease of control over cavity and interconnecting channel diameters and for full interconnectivity at lower porosities. The scaffolds demonstrated high mechanical properties for PLGA alone (>50 MPa), in vitro biocompatibility, and maintenance of osteoblast phenotype, making them promising for a highly controllable bone tissue engineering scaffold.

Cellulose nanocrystals are promising as a new class of reinforcing material for the preparation of nanostructured composites. We report here the preparation of cellulose nanocrystal multilayer composites with poly(diallyldimethylammonium chloride) using layer-by-layer assembly (LBL) technique. The LBL assembly was characterized with UV-Vis spectroscopy and ellipsometry. The average thickness of a single bilayer was found to be 11 nm. AFM and SEM characterization revealed uniform coverage and densely packed cellulose crystal surface.