Self-assembling multidomain peptides tailor biological responses through biphasic release

Vivek A. Kumar, Nichole L. Taylor, Siyu Shi, Navindee C. Wickremasinghe, Rena N. D'Souza, Jeffrey D. Hartgerink

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Delivery of small molecules and drugs to tissues is a mainstay of several tissue engineering strategies. Next generation treatments focused on localized drug delivery offer a more effective means in dealing with refractory healing when compared to systemic approaches. Here we describe a novel multidomain peptide hydrogel that capitalizes on synthetic peptide chemistry, supramolecular self-assembly and cytokine delivery to tailor biological responses. This material is biomimetic, shows shear stress recovery and offers a nanofibrous matrix that sequesters cytokines. The biphasic pattern of cytokine release results in the spatio-temporal activation of THP-1 monocytes and macrophages. Furthermore, macrophage-material interactions are promoted without generation of a proinflammatory environment. Subcutaneous implantation of injectable scaffolds showed a marked increase in macrophage infiltration and polarization dictated by cytokine loading as early as 3 days, with complete scaffold resorption by day 14. Macrophage interaction and response to the peptide composite facilitated the (i) recruitment of monocytes/macrophages, (ii) sustained residence of immune cells until degradation, and (iii) promotion of a pro-resolution M2 environment. Our results suggest the potential use of this injectable cytokine loaded hydrogel scaffold in a variety of tissue engineering applications.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalBiomaterials
Volume52
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Keywords

  • Inflammation
  • Macrophage polarization
  • Multi-domain peptide
  • Self-assembly

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