MODIFICATION
A -- DEFENSE SCIENCES RESEARCH AND TECHNOLOGY
- Notice Date
- 1/17/2002
- Notice Type
- Modification
- Contracting Office
- Other Defense Agencies, Defense Advanced Research Projects Agency, Contracts Management Office, 3701 North Fairfax Drive, Arlington, VA, 22203-1714
- ZIP Code
- 22203-1714
- Solicitation Number
- BAA01-42
- Response Due
- 8/29/2002
- Archive Date
- 8/30/2002
- Point of Contact
- Joseph Bielitzki, DARPA Program Manager, Phone 703-696-5278, Fax 703-696-3999,
- E-Mail Address
-
none
- Description
- BAA 01-42, ADDENDUM 8, SPECIAL FOCUS AREA: ENGINEERED TISSUE CONSTRUCTS (ETC). The Defense Sciences Office is interested in innovative proposals to develop the technologies and science for supporting efforts leading to the creation of a three-dimensional ex vivo human immune system. This system will be used for testing new vaccine constructs and immunomodulators that provide superior protection against threat agents. The ETC program seeks to develop reliable methodologies that will accelerate the science and technology base necessary to achieve 3-D tissue engineering and to define the spatial and temporal requirements necessary to expand its applicability. This program intends to encourage multi-disciplinary teams, bringing together a combination of science and engineering communities to achieve its goals. The ability to fabricate functional 3-D ex vivo tissue constructs is limited by current methodologies and materials in 3-D printing, culture methods, bioscaffolding, stem cell biology, and the controlled differentiation of cells. ETC is a two-phase program addressing these limitations. Phase 1 will establish proof-of-concept that human stem cells can be reliably differentiated into multiple immune functions within an in vitro 3-D culture system. The capability to divert stem cells into multiple immune lineages is a Phase 1 milestone. Such differentiation should be verifiable by the presence of recognized surface markers characteristic of the cell type. Phase 1 targets include differentiation into early lymphoid lineages, Pro B cells and Pro T Cells, and early myeloid lineages. ETC should define the spatial and temporal requirements of the matrix, cells, trophic factors, and differentiation factors within the culture environment leading to interactive organ constructs. Phase 2 will focus on continuation of Phase 1 technologies and on producing interactive engineered tissue constructs of the functional elements of the immune system required for both cellular and humeral responses and its appropriate validation. Proposals in response to this BAA should describe an 18-24 month Phase 1 program only. Phase 2 proposals will be requested at a later date. Proposers for Phase 1 should consider research efforts that address one or more of the following three technical areas: 1) A 3-D conformal printing system: the printing system should have capabilities for conformal deposition of scaffolding, cells, and differentiation factors. Three-dimensional configurations should be adaptable and capable of utilizing computer-aided design or computer-aided machine technologies (CAD/CAM) to meet the anatomic requirements of the construct. In addition, methods to athermally ablate and/or sculpt the construct are desired; 2) A modular 3-D culture system and/or bioreactor: the 3-D culture system and/or bioreactor should optimize cellular growth, differentiation, and a functional stationary phase. The design should be modular and adaptable to cellular manipulation and harvesting, and provide an environment that allows chemical and cellular signals to traffic between tissue constructs for appropriate processing of antigen. The growth chamber should be accessible for deposition, ablation, sampling and other manipulations of the 3-D tissue construct; 3) New concepts in the materials to be printed or deposited: bioscaffolding should bind cells selectively, promote cellular differentiation and provide spatial interactions between multiple cell types and lineages. Consideration should be given to expanding the complement of types of bioscaffolds beyond polymers and hydrogels. New concepts and methods that provide the release of differentiation factors in the appropriate sequence, concentration and duration, that enhance the binding of specific cell types, and/or that attract stem cells to an environment should be explored. A significant objective will be the ability to harvest and expand to scalable level human stem cell populations. Such expansion is necessary to assure a stable source of cells to replicate the production of all elements of the ex vivo immune system. Ideally, such cells would be derived from a human precursor cell prior to the development of immunogenicity. It is anticipated that the final constructs will contain cells derived from all germ layers and immune tolerance is essential for the long-term functionality of the system. Progress in this program will critically depend on the formation of well-managed interdisciplinary efforts drawing on expertise from such areas as developmental biology, immunology, structural biology, chemical engineering, materials science, electrical engineering, systems engineering, and computer science. In addition, it is expected that a strong mathematic modeling component be included wherever necessary. Whatever the interdisciplinary composition of the team, its members will need to be sharply and collectively focused on achieving the Phase 1 objectives. A limited number of smaller efforts focused on developing unique approaches to overcoming specific technology challenges may be supported with an eye towards incorporating them into the integrated team efforts by the end of the program. We invite white papers (10 pages or less) in response to this announcement. The white paper should be organized as follows: 1) The idea. Which capabilities will you attempt to develop? 2) The approach. How do you plan to demonstrate these capabilities within the 18-24 month period of funding? What additional capabilities do you envision will be enabled by your ideas? What are the research challenges, and how will they be addressed? What is unique or revolutionary about your approach? Every white paper must describe the 18-month quantitative milestone(s) that will be achieved in order to demonstrate progress in reaching your specific goals; 3) The cost. What is your cost estimate for resources required for the proposed time line? This section should include a clear description of the human resources needed, as well as funding. A management plan that describes how the different disciplines represented on the team will be integrated to generate a capability demonstration within 18 months is critical; and 4) A brief description of the technical expertise of the principal investigator and the key team members should be provided. While there is no formal date for submission, white papers sent within 30 days of publication of this Addendum will be evaluated immediately upon receipt and proposers will be notified within 10 business days of receipt if a full proposal will be requested. White papers submitted after the 30-day time period will be considered on a case-by-case basis. White paper submissions may be made by attachment to an e-mail sent to dsobaa01-42@darpa.mil. Word 97 or higher is recommended but not required. Embedded text and Postscript are also acceptable. Please put "Engineered Tissue Constructs" in the title of the white paper. The body of the e-mail must include name, mailing address, phone number, and fax number. If submitting by U.S. mail, the proposers must submit an original and five (5) copies of the white paper to DARPA/DSO, ATTN: Engineered Tissue Constructs, BAA 01-42, Addendum 8, 3701 North Fairfax Drive, Arlington, VA 22203-1714. Not withstanding the disposition of white papers, DARPA will respond to full proposals expeditiously, upon scientific review, with the first wave of proposals being reviewed within 75 days after publication of this addendum. Regardless of the recommendation of the white paper, the decision to submit a full proposal is the responsibility of the proposer. White papers and proposals will not be accepted by way of facsimile transmission. For general administrative questions, please refer to the original CBD announcement, BAA 01-42, of September 4, 2001.
- Record
- SN20020119/00015902-020118090842 (fbodaily.com)
- Source
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