title: A phage-targeting strategy for the design of spatiotemporal drug delivery from grafted matrices.
abstract: BACKGROUND
  The natural response to injury is dynamic and normally consists of complex temporal and spatial cellular changes in gene expression, which, when acting in synchrony, result in patent tissue repair and, in some instances, regeneration. However, current therapeutic regiments are static and most rely on matrices, gels and engineered skin tissue. Accordingly, there is a need to design next-generation grafting materials to enable biotherapeutic spatiotemporal targeting from clinically approved matrices. To this end, rather then focus on developing completely new grafting materials, we investigated whether phage display could be deployed onto clinically approved synthetic grafts to identify peptide motifs capable of linking pharmaceutical drugs with differential affinities and eventually, control drug delivery from matrices over both space and time.
  
  
  METHODS
  To test this hypothesis, we biopanned combinatorial peptide libraries onto different formulations of a wound-healing matrix (Integra®) and eluted the bound peptides with 1) high salt, 2) collagen and glycosaminoglycan or 3) low pH. After three to six rounds of biopanning, phage recovery and phage amplification of the bound particles, any phage that had acquired a capacity to bind the matrix was sequenced.
  
  
  RESULTS
  In this first report, we identify distinct classes of matrix-binding peptides which elute differently from the screened matrix and demonstrate that they can be applied in a spatially relevant manner.
  
  
  CONCLUSIONS
  We suggest that further applications of these combinatorial techniques to wound-healing matrices may offer a new way to improve the performance of clinically approved matrices so as to introduce temporal and spatial control over drug delivery.
authors.affiliation: Department of Surgery, Division of Trauma, Surgical Critical Care and Burns, University of California San Diego School of Medicine, 200 W, Arbor Dr,, San Diego, CA 92103-8236 USA. anbaird@ucsd.edu.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Sawada
authors.forename: Carrie Y
authors.initials: CY
authors.lastname: Peterson
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Gonzalez
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Potenza
authors.forename: Barbara
authors.initials: B
authors.lastname: Mueller
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.forename: Brian P
authors.initials: BP
authors.lastname: Eliceiri
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird