Self-assembling multidomain peptides tailor biological responses through biphasic release.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Immunology

Background:

• Localized drug delivery offers advantages over systemic approaches for challenging tissue healing.
• Current tissue engineering strategies require advanced materials for controlled biological responses.

Purpose of the Study:

• To develop and characterize a novel multidomain peptide hydrogel for localized cytokine delivery.
• To evaluate the hydrogel's ability to modulate immune cell behavior for tissue regeneration.

Main Methods:

• Synthetic peptide chemistry and supramolecular self-assembly were used to create the hydrogel.
• The hydrogel's nanofibrous matrix was designed to sequester and release cytokines in a biphasic manner.
• Injectable scaffolds were implanted subcutaneously to assess in vivo performance, including immune cell infiltration and scaffold degradation.

Main Results:

• The peptide hydrogel demonstrated biomimetic properties, shear stress recovery, and cytokine sequestration.
• Biphasic cytokine release led to spatio-temporal activation of monocytes and macrophages without inducing inflammation.
• Subcutaneous implantation resulted in increased macrophage infiltration and M2 polarization, with complete scaffold resorption within 14 days.

Conclusions:

• The injectable hydrogel scaffold effectively recruits and sustains immune cells, promoting a pro-resolution M2 environment.
• This novel material shows significant potential for various tissue engineering applications requiring controlled immune modulation.