Three-Dimensional Scaffolds for Bone Marrow Tissue Constructs

DESCRIPTION (provided by applicant): The overall RandD cycle for drugs costs 300-800 million in capital and up to 10-12 years in time. One of the reasons for such great cost is that the vast majority of drug candidates are screened out at the stages of animal and human trials. More efficient methods of testing of drugs at the stage of ex-vivo studies, which are substantially less expensive than animal and human testing cycles, will lead to improvement of the success rate of preclinical trials, accelerate on of drug discovery, reduction of the cost of pharmaceutical development, and better drugs. Efficacy of in-vitro testing can be significantly increased provided that better ex-vivo models for different organs and tissues are developed. In this Phase I STTR project involving a start-up company Nico Technology Corporation (NTCorp), University of Michigan, University of Texas Medical Branch, and Fred Hutchinson Cancer Research Center we propose the development of a new type of 3D scaffold that can (1) rectify the problems of existing 3D matrixes and (2) provide the pharmaceutical industry the possibility to develop convenient and reliable protocols for drug assessment in organ replicas, and in particular ex-vivo bone marrow construct. Phase I of the project is aimed at the proof-of-concept demonstration that 3D scaffolds based on inverted colloidal crystal (ICC) scaffolds with remarkable resemblance of its 3D topology to that of bone marrow can be produced. They will be made from hydrogel and enable surface marker assays traditionally used in drug testing. Specific Aims (SA) for the project. SA1: Manufacturing of Cell-Adhesive ICC Scaffolds from Hydrogel; SA2: Evaluation of Stem cell Replication Functionality in a Bone Marrow Replica from ICC Scaffolds. In perspective, the bone marrow replica can be a convenient model system for the use in anticancer and antiviral drugs as kits and assays both for academic and industrial researchers. This model has no current analogs and can significantly improve the traditional 2D cell culture discovery tools with a potential to reduce the drug failures at animal and human trials stages. PUBLIC HEALTH RELEVANCE: Evaluation of drugs can be significantly accelerated by testing them in tissue analogs, which require a suitable 3D matrix that affords engineering of different tissues and optical monitoring of the cellular processes in it. In this project we propose manufacturing of transparent 3D hydrogel scaffolds with inverted colloidal crystal (ICC) geometry. Commercial production of ICC scaffolds will provide drug manufacturers with a standardized, reliable, reproducible, user- friendly 3D matrix that can be used in a variety of ex-vivo drug testing procedures that has a potential to reduce the cost and shorten the time of drug development.