title: Self-assembling multidomain peptides tailor biological responses through biphasic release.
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.
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Vivek A
authors.initials: VA
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Nichole L
authors.initials: NL
authors.lastname: Taylor
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Siyu
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Navindee C
authors.initials: NC
authors.lastname: Wickremasinghe
authors.affiliation: School of Dentistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Rena N
authors.initials: RN
authors.lastname: D'Souza
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77030, USA. Electronic address: jdh@rice.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hartgerink
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D057139:Nanofibers / Q000737:chemistry / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry*; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D016207:Cytokines; D010455:Peptides
keywords: Inflammation; Macrophage polarization; Multi-domain peptide; Self-assembly
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