A phage-targeting strategy for the design of spatiotemporal drug delivery from grafted matrices

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.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.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.Synthetic grafts for full-thickness acute and chronic wounds have emerged as an important tool in the surgical management of cutaneous injuries [1-5]. Recognizing that significant improvements are still needed, several investigators have proposed that a combination of matrices with biotherapeutics would be an important direction in the development of next generation grafts [6-11]. Although it may be possible to create new matrices de novo, one promising approach has involved adding biotherapeutics and gene-based medicines to commonly used and clinically approved matrices before their deployment [1,2,6,7,10-16]. Athough this approach builds on a significant amount of clinical experience, the results have unfortunately been variable, and furthermore, the approach is not amenable to treatment after graft placement. For example, gene-activated matrices (GAM) [17-21] require preformulation of genes within collagen matrices and, although we have used wound-healing matrices (Integra？; Integra LifeSciences, Plainsboro, NJ, USA) in animal models of wound healing to evaluate exogenous gene delivery at the site of injury after deployment [21,2