DEVELOPMENT OF ADVANCED BIOMATERIALS
 
RELEASE DATE:  December 9, 2002
 
RFA:  EB-03-009

National Institute of Biomedical Imaging and Bioengineering (NIBIB)
 (http://www.nibib.nih.gov)  

APPLICATION RECEIPT DATE:  March 27, 2003
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

Biomaterials are fundamental to the design and development of a wide 
variety of medical devices and implants.  In addition, ongoing advances 
in understanding cell biology, wound healing, and targeted drug effects 
are creating opportunities for the use of biomaterials in unprecedented 
ways.  The National Institute of Biomedical Imaging and Bioengineering 
(NIBIB) is in the process of building a scientific program to enhance 
the development of advanced biomaterials to meet the current and future 
needs for biomaterials in biology and medicine. The NIBIB seeks 
investigator-initiated applications for either NIH Research Project 
Grant (R01) awards or Exploratory/Developmental Research Grant (R21) 
awards for the development of novel biomaterials that can be used for a 
broad spectrum of biological and medical applications such as 
implantable medical devices, tissue engineering, drug and gene 
delivery, imaging agents, materials for minimally invasive surgery, and 
biosensors. The approach to biomaterials research should be mechanistic 
and in the context of fundamental engineering principles, design 
criteria, and strategies, including theory and modeling.  The scope may 
cover the basic science and engineering aspects of biomaterials 
including their mechanical, physical, chemical, and biological 
properties, relevant design and production characteristics of devices 
constructed of these materials, and their clinical performance. 
Collaborative interdisciplinary research involving biomaterials 
scientists, materials scientists, biologists, physiologists, 
clinicians, engineers, and experts in any of the quantitative sciences 
is strongly encouraged.  Innovative industrial partnerships are also 
welcome.  
 
RESEARCH OBJECTIVES 

Advances in the fundamental understanding of cell and molecular 
biology, tissue engineering principles, targeted drug effects, wound 
healing and other biomedical processes, together with the development 
of new enabling technologies such as micro, nano, and bio-inspired 
fabrication methods, have the potential to drive the design and 
development of new biomaterials useful for medical applications at an 
unprecedented rate.  At the present time however, the most common 
biomaterials in clinical use are generally those chosen from a handful 
of well-characterized and available off-the-shelf metals and polymers 
due to few suppliers of new biomaterials, time-to-market pressures as 
well as regulatory requirements.  The purpose of this Request for 
Applications (RFA) is to seize the opportunity to significantly improve 
the clinical usefulness of biomaterials by promoting and supporting 
research and development of novel biomaterials with improved biological 
and mechanical properties and new concepts and strategies for 
fabrication methods that can lead to biomaterials that are truly 
biocompatible and bio-responsive.  The focus is on biomaterials 
relevant to a broad range of applications such as implantable medical 
devices, tissue engineering, drug and gene delivery, imaging agents, 
materials for minimally invasive surgery and biosensors.  

Applications submitted in response to this RFA should include research 
on the design, synthesis, characterization, processing, and/or 
manufacturing of novel biomaterials including biostable materials as 
well as bioresorbable and scaffold materials. Proposals should fulfill 
one or more of the following criteria:  1) work aimed at integrating 
pieces of knowledge into larger, more generally applicable engineering 
design rules and principles; 2) work aimed at the development of 
fundamental, quantitative knowledge of cell-material interactions; 3) 
work aimed at the development of new strategies and approaches toward 
design optimization of new biomaterials, implants or devices.  

We encourage multidisciplinary partnerships and partnerships between 
academic and industrial scientists.  Applications focused on a clinical 
problem with a bedside to bench to bedside approach are also encouraged 
as are high risk/high impact research proposals as opposed to 
incremental innovation and development.  Research addressing these 
needs may include, but are not limited to:

o   The design of products and materials incorporating smart materials 
such as electroactive, shape memory alloys, piezoelectric devices, 
and magnetostrictive materials. 

o   The development of highly efficient active materials that mimic 
biological actuation, sensing, and conduction.   Biomimetic refers 
to human-made processes, substances, devices, or systems that 
imitate nature or that learn from, and copy, biological systems. 

o   Biomolecular self-assembly, nanobiomaterials, nano- and 
microfabrication, soft lithography, molecular imprinting, chemical 
modification and organic and bioorganic synthesis.

o   New synthetic materials for use as gene vectors and drug delivery 
vehicles.

o   New materials for use as image enhancers and contrast agents with an 
emphasis on the development of new polymeric or nanoparticle-based 
contrast agents.

o   Biocompatibility including the research and development of methods 
to access biocompatibility: low cost in vivo and in vitro models 
with a focus on reliability, accelerated testing, failure analysis, 
imaging, and improved understanding of the biology-biomaterials 
interface.

o   Molecular/cellular interfacial interactions including protein 
adsorption, cell adhesion, biomolecule function at interfaces, 
nonfouling surfaces and bioactive surfaces.

o   Design and development of new composite structures with micro- or 
macroscopic level domain structures for enhancement of targeted 
design properties such as modulus or compliance.

o   New platforms of absorbable materials with controlled strength loss 
and mass absorption profiles.

o   Informatics and modeling tools for the rational design and 
structure-properties development in biomaterials.

o   Design and development of bioreactor or bio-inspired methods for the 
production of structured biomaterials.

o   New concepts and strategies for self-healing materials, e.g. auto-
repair of fatigue cracks in structural implants.

MECHANISM OF SUPPORT

This RFA will use the NIH investigator-initiated research grant award 
mechanism (R01) and the development/exploratory grant award mechanism 
(R21).  As an applicant you will be solely responsible for planning, 
directing, and executing the proposed project.  This RFA is a one-time 
solicitation.  Future unsolicited, competing-continuation R01 
applications based on this project will compete with all investigator-
initiated applications and will be reviewed according to the customary 
peer review procedures.  The anticipated award date is September 30, 
2003.

The R01 mechanism is recommended for applications that emphasize basic 
discovery or cross-cutting research that addresses specific aspects of 
biomaterials research.   Research periods associated with the R01 
proposals are limited to five years with no cap on budget amount.   

The R21 Exploratory/Developmental Award supports exploratory or 
developmental research aimed at proof-of-principle for high-risk 
projects where no or very little preliminary data is available.  An R21 
application can be for up to two years with a maximum budget request of 
$275,000 direct costs for the 2-year period and a maximum page limit of 
15 pages.  R21 applications are not renewable.  If sufficient results 
are generated during the term of the award, investigators are 
encouraged to apply for further funding through the R01 mechanism (or 
other appropriate mechanisms).
  
This RFA uses just-in-time concepts.  It also uses the modular as well 
as the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  
Specifically, if you are submitting an application with direct costs 
(including total costs of consortium arrangements) in each year of 
$250,000 or less, use the modular format.  Otherwise follow the 
instructions for non-modular research grant applications.

FUNDS AVAILABLE 
 
The NIBIB intends to commit approximately $8,000,000 in FY 2003 to fund 
20 to 30 new and/or competitive continuation grants in response to this 
RFA. An applicant may request a project period of up to 5 years for an 
R01 and a project period of up to 2 years for an R21.  Budgets for 
direct costs of up to $275,000 for the 2-year period will be accepted 
for an R21.  There is no budget limitation for R01 applications.

Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size and 
duration of each award will also vary. Although the financial plans of 
the NIBIB provide support for this program, awards pursuant to this RFA 
are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications. At this time, it is not 
known if this RFA will be reissued.
 
ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the 
following characteristics:

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   

SPECIAL REQUIREMENTS 

General Clinical Research Centers:  Applicants from institutions that 
have a General Clinical Research Center (GCRC) funded by the NIH 
National Center for Research Resources may wish to identify the GCRC as 
a resource for conducting the proposed research.  If so, a letter of 
agreement from either the GCRC program director or principal 
investigator should be included with the application.

Grantee Meetings:  Principal Investigators will be required to attend 
an annual meeting in the Bethesda, MD region organized by NIBIB.  
Investigators must include travel to this meeting as part of the budget 
request and state a willingness to participate in this meeting.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
two areas:  scientific/research and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

Christine A. Kelley, Ph.D.
Acting Director
Division of Bioengineering
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
Suite 200
6707 Democracy Blvd.
Bethesda, MD  20892-5469
Telephone:  (301) 451-4778
Fax: (301) 480-4973
Email: [email protected]

o Direct your questions about financial or grants management matters 
to:

Ms. Nancy Curling
Division of Extramural Activities
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
Suite 900
6707 Democracy Blvd. 
Bethesda, MD  20892
Telephone:  (301) 451-4786
Fax:  301-480-4974
Email:  [email protected]
 
SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email: [email protected].
 
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in 
a modular grant format.  The modular grant format simplifies the 
preparation of the budget in these applications by limiting the level 
of budgetary detail.  Applicants request direct costs in $25,000 
modules.  Section C of the research grant application instructions for 
the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and five signed, 
photocopies, in one package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
APPLICATION PROCESSING: Applications must be received by the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is 
essentially the same as one already reviewed. This does not preclude 
the submission of substantial revisions of applications already 
reviewed, but such applications must include an Introduction addressing 
the previous critique. 

Please Note: As of November 27, 2001, all applications and other 
deliveries to the Center for Scientific Review must come via courier 
delivery or the USPS.  Applications delivered by individuals to the 
Center for Scientific Review will no longer be accepted.  For 
additional information, see the NIH Guide Notice 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIBIB. Incomplete applications will be 
returned to the applicant without further consideration.  And, if the 
application is not responsive to the RFA, CSR staff may contact the 
applicant to determine whether to return the application to the 
applicant or submit it for review in competition with unsolicited 
applications at the next appropriate NIH review cycle.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the CSR in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 
will:

o Receive a written critique
o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate National Advisory 
Council. 
 
REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these 
criteria in assigning your application's overall score, weighting them 
as appropriate for each application.  Your application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward. 

(1) SIGNIFICANCE:  Does your study address an important problem? If the 
aims of your application are achieved, how do they advance scientific 
knowledge?  What will be the effect of these studies on the concepts or 
methods that drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project 
challenge existing paradigms or develop new methodologies or 
technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to your 
experience level as the principal investigator and to that of other 
researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will be reviewed with respect to the following:

o TEAM APPROACH:  The inclusion of researchers with divergent 
backgrounds, for example, the partnering of an engineer, a physiologist 
and/or a clinician.

o R21 MECHANISM ONLY:  Since the R21 mechanism is intended to encourage 
exploratory/developmental research, proposals submitted as an R21 will 
be reviewed based on their high risk/high impact potential and whether 
or not the proposal is significantly distinct from those traditionally 
submitted through the R01 mechanism.  For example, R21 projects 
designed to produce incremental advances in knowledge will not be 
considered.  

o PROTECTIONS:  The adequacy of the proposed protection for humans, 
animals, or the environment, to the extent they may be adversely 
affected by the project proposed in the application.

o INCLUSION:  The adequacy of plans to include subjects from both 
genders, all racial and ethnic groups (and subgroups), and children as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See 
Inclusion Criteria included in the section on Federal Citations, below)

o BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Application Receipt Date: March 27, 2003
Peer Review Date: June/July, 2003
Council Review: September, 2003
Earliest Anticipated Start Date: September 30, 2003

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy 
of the NIH that women and members of minority groups and their sub-
populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect to the health of 
the subjects or the purpose of the research. This policy results from 
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS: The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 
1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for research 
involving human subjects.  You will find this policy announcement in the 
NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of 
research on hESCs can be found at 
http://grants.nih.gov/grants/stem_cells.htm and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see 
http://escr.nih.gov).   It is the responsibility of the applicant to 
provide the official NIH identifier(s)for the hESC line(s)to be used in 
the proposed research.  Applications that do not provide this 
information will be returned without review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom of 
Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, Internet 
addresses (URLs) should not be used to provide information necessary to 
the review because reviewers are under no obligation to view the 
Internet sites.   Furthermore, we caution reviewers that their anonymity 
may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.286 and 93.287 and is not subject to 
the intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 
USC 241 and 284) and administered under NIH grants policies described 
at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.

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