Bioactive fibrous scaffolds with programmable release of polypeptides regulate inflammation and extracellular matrix remodeling

Author:

Xiang Zehong12,Guan Xinghua12,Ma Zhifang1,Shi Qiang123,Panteleev Mikhail45,Ataullakhanov Fazly I45

Affiliation:

1. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China

2. University of Science and Technology of China , Hefei, Anhui 230026, China

3. Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function, Soochow University , Suzhou 215123, China

4. Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology , Moscow 117198, Russia

5. Faculty of Physics, Lomonosov Moscow State University , Moscow 119991, Russia

Abstract

AbstractInflammation manipulation and extracellular matrix (ECM) remodeling for healthy tissue regeneration are critical requirements for tissue engineering scaffolds. To this end, the bioactive polycaprolactone (PCL)-based scaffolds are fabricated to release aprotinin and thymosin β4 (Tβ4) in a programmable manner. The core part of the fiber is composed of hyaluronic acid and Tβ4, and the shell is PCL, which is further coated with heparin/gelatin/aprotinin to enhance biocompatibility. The in vitro assay demonstrates that the controlled release of aprotinin prevents initial excessive inflammation. The subsequent release of Tβ4 after 3 days induces the transition of macrophages from M1 into M2 polarization. The manipulation of inflammatory response further controls the expression of transforming growth factor-β and fibroblast activation, which oversee the quantity and quality of ECM remodeling. In addition, the gradual degradation of the scaffold allows cells to proliferate within the platform. In vivo implant evaluation convinces that PCL-based scaffolds possess the high capability to control the inflammatory response and restore the ECM to normal conditions. Hence, our work paves a new way to develop tissue engineering scaffolds for inflammation manipulation and ECM remodeling with peptide-mediated reactions.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Biomaterials

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