David W. Grainger
Distinguished Professor of Pharmaceutics and
Pharmaceutical Chemistry and of Biomedical Engineering and
Adjunct Professor of Chemistry
B.A. Dartmouth College
Ph.D. University of Utah
David Grainger's Lab Page
David Grainger's PubMed Literature Search
Biological Chemistry Program
Biomaterials and Drug Delivery, Materials in Medicine, Nanomaterials toxicity, Diagnostics
Research
Biomedical materials applications
The Grainger group is broadly interested in applications of materials in medicine,
including surgical implants, drug delivery systems, diagnostic assays, regenerative
medicine, biotechnology and infection. Research requires broad use of many tools and
techniques to yield new knowledge about these complex systems. Materials synthesis,
extensive characterization, drug formulation, in vitro assays and in vivo testing
often comprise a typical student research program.
Diagnostic assays
Many new innovations in capabilities to capture, detect and identify organisms (e.g.,
viruses, bacteria), proteins (disease markers), and other important analytes require
interactions of biological samples with captures surfaces to generate assay signals.
This is relevant to ELISA, microarray, optical, and lateral flow assays. Discrimination
of analyte from plentiful noise in biological milieu determines assay performance.
We focus on improving nucleic acid microarray performance by first understanding how
DNA is immobilized into micron spots for these assays, then studying complementary
DNA target capture to these spots. We use many surface analytical methods to produce
chemical and physical information on DNA at interfaces. We are among first on record
to specifically quantify amounts of DNA immobilized in arrays, and the efficiency
of DNA analyte capture in array surface spots of decreasing size, cross-correlating
DNA on surfaces with various analytical methods. We are moving to immobilized protein
arrays as the next frontier.
Cell and bacterial colonization of surfaces
Many biomaterials seek to encourage cell attachment to integrate these materials
into biological systems or human tissue. Risks associated with any biomaterials implanted
into tissue include the hallmark foreign body response (i.e., rejection and unresolved
inflammation), infection, and blood reactivity. Our group examines two aspects of
these adverse reactions: 1) inflammatory cellular reactions with implanted materials,
and 2) bacterial adhesion and infection of biomaterials. The major cellular mediator
of the foreign body response is the macrophage. We have studied various aspects of
macrophage interrogation of implant materials, markers for their reactivity and mechanisms
of their cell-surface adhesion. Additionally, we study bacterial attachment to surfaces
and methods to improve microcidal strategies to prevent implant-centered infection.
Drug delivery and combination medical devices
Biomaterials suffer from numerous shortcomings: drug delivery from devices is being
increasingly used to help mitigate implant problems within tissue. These medical devices
that both function in prosthetic replacement as well as release drugs are termed 'combination
devices'. Our interests lie in producing delivery systems for new drug families from
the surface of implantable surgical devices. These include cardiovascular and orthopedic
devices that release small and large biopharmaceutical drugs, and antibiotic release
from implants. Additionally, we have produced a novel living vaccine delivery system
for wildlife that has broad applicability to remote delivery of many other biological
therapeutics.
References
Diagnostic assays
- Rao AN, Grainger DW (2014) Biophysical Properties of Nucleic Acids at Surfaces Relevant to Microarray Performance. Biomater Sci, 2(4):436-471
- Romanov V, Davidoff SN, Miles AR, Grainger DW, Gale BK, Brooks BD (2014) A critical comparison of protein microarray fabrication technologies. Analyst, 139(6):1303-26
Cell and bacterial colonization of surfaces
- Avula MN, Rao AN, McGill LD, Grainger DW, Solzbacher F (2014) Foreign body response to subcutaneous biomaterial implants in a mast cell-deficient Kit(w-Sh) murine model. Acta Biomater, 10(5):1856-63
- Avula MN, Rao AN, McGill LD, Grainger DW, Solzbacher F (2013) Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib. Biomaterials, 34(38):9737-46
- Grainger DW, van der Mei HC, Jutte PC, van den Dungen JJ, Schultz MJ, van der Laan BF, Zaat SA, Busscher HJ (2013) Critical factors in the translation of improved antimicrobial strategies for medical implants and devices. Biomaterials, 34(37):9237-43
- Grainger DW (2013) All charged up about implanted biomaterials. Nat Biotechnol, 31(6):507-9
Drug delivery and combination medical devices
- Astashkina AI, Jones CF, Thiagarajan G, Kurtzeborn K, Ghandehari H, Brooks BD, Grainger DW (2014) Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model. Biomaterials, 35(24):6323-31
- Wang Y, Liu J, Zhang J, Wang L, Chan J, Wang H, Jin Y, Yu L, Grainger DW, Ying W (2014) A cell-based pharmacokinetics assay for evaluating tubulin-binding drugs. Int J Med Sci, 11(5):479-87
- Astashkina A, Grainger DW (2014) Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments. Adv Drug Deliv Rev, 69-70:1-18
- Brooks BD, Sinclair KD, Davidoff SN, Lawson S, Williams AG, Coats B, Grainger DW, Brooks AE (2014) Molded polymer-coated composite bone void filler improves tobramycin controlled release kinetics. J Biomed Mater Res B Appl Biomater, 102(5):1074-83
- Wang Y, Grainger DW (2013) Developing siRNA therapies to address osteoporosis. Ther Deliv, 4(10):1239-46
- Munger MA, Radwanski P, Hadlock GC, Stoddard G, Shaaban A, Falconer J, Grainger DW, Deering-Rice CE (2014) In vivo human time-exposure study of orally dosed commercial silver nanoparticles. Nanomedicine, 10(1):1-9
