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Pravastatin regulates host foreign-body reaction to polyetheretherketone implants via miR-29ab1-mediated SLIT3 upregulation

Author:
Liao, Yun, Ouyang, Liping, Ci, Lei, Chen, Baohui, Lv, Dan, Li, Qin, Sun, Yingxiao, Fei, Jian, Bao, Shisan, Liu, Xuanyong, Li, Ling
Source:
Biomaterials 2019 v.203 pp. 12-22
ISSN:
0142-9612
Subject:
angiogenesis, biocompatible materials, drugs, encapsulation, knockout mutants, mass transfer, medical equipment, mice, pravastatin
Abstract:
Host rejection to biomaterials can induce uncontrolled foreign-body reactions (FBR), resulting in a dense fibrous encapsulation that blocks mass transport and/or communication between the host and the implant. Adequate angiogenesis between the body and the implant has been implicated as a key regulator for overcoming FBR. Thus, approaches for stimulating neovascularization and/or suppressing FBR are under investigation. In this study, pravastatin (Pra) was loaded onto a 3D network surface of sulfonated polyetheretherketone (SP) to achieve superior local drug effects. The SP loaded with Pra (SP-Pra) promoted angiogenesis and mitigated FBR via miR-29 dependent SLIT3 upregulation in wild-type (WT) mice. miR-29a and miR-29b1 were significantly downregulated in the SP-Pra capsule compared to levels in the SP capsule, while SLIT3 and neovascularization were substantially upregulated in WT mice. However, the above effects presented in the WT mice were not detected in miR-29ab1 knockout mice which was generated by the CRISPR/Cas9 approach. Overall, the results suggest that miR-29 plays a critical role in reducing FBR to these implants by targeting SLIT3. Suppression of FBR by SP-Pra implants offers the potential to improve the performance of current medical devices.
Agid:
6333216