Bioactive engineered scaffolds based on PCL-PEG-PCL and tumor cell-derived exosomes to minimize the foreign body reaction

Zehong Xiang; Xinghua Guan; Zhifang Ma; Qiang Shi; Mikhail Panteleev; Fazly I Ataullakhanov

doi:10.1016/j.bbiosy.2022.100055

Bioactive engineered scaffolds based on PCL-PEG-PCL and tumor cell-derived exosomes to minimize the foreign body reaction

Biomater Biosyst. 2022 Jun 14:7:100055. doi: 10.1016/j.bbiosy.2022.100055. eCollection 2022 Aug.

Authors

Zehong Xiang^{1

2}, Xinghua Guan^{1

2}, Zhifang Ma¹, Qiang Shi^{1

2

3}, Mikhail Panteleev^{4

5}, Fazly I Ataullakhanov^{4

5}

Affiliations

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 Natl Res Ctr Pediat Hematol Oncol, 1 Samory Mashela St, Moscow, 117198, Russia.
⁵ Faculty of Physics, Lomonosov Moscow State University, Leninskie Gory, 1, build. 2, GSP-1, Moscow 119991, Russia.

Abstract

Long-term presence of M1 macrophages causes serious foreign body reaction (FBR), which is the main reason for the failure of biological scaffold integration. Inducing M2 polarization of macrophages near scaffolds to reduce foreign body response has been widely researched. In this work, inspired by the special capability of tumor exosomes in macrophages M2 polarization, we integrate tumor-derived exosomes into biological scaffolds to minimize the FBR. In brief, breast cancer cell-derived exosomes are loaded into polycaprolactone-b-polyethylene glycol-b-polycaprolactone (PCL-PEG-PCL) fiber scaffold through physical adsorption and entrapment to constructed bioactive engineered scaffold. In cellular experiments, we demonstrate bioactive engineered scaffold based on PCL-PEG-PCL and exosomes can promote the transformation of macrophages from M1 to M2 through the PI3K/Akt signaling pathway. In addition, the exosomes release gradually from scaffolds and act on the macrophages around the scaffolds to reduce FBR in a subcutaneous implant mouse model. Compared with PCL-PEG-PCL scaffolds without exosomes, bioactive engineered scaffolds reduce significantly inflammation and fibrosis of tissues around the scaffolds. Therefore, cancer cell-derived exosomes show the potential for constructing engineered scaffolds in inhibiting the excessive inflammation and facilitating tissue formation.

Keywords: Engineered scaffolds; Exosomes; Inflammation; Macrophages; Polarization.