Functional supramolecular bioactivated electrospun mesh improves tissue ingrowth in experimental abdominal wall reconstruction in rats

被引:33
作者
da Cunha, Marina Gabriela M. C. Mori [1 ,2 ]
Arts, Boris [3 ,4 ]
Hympanova, Lucie [1 ,2 ,5 ]
Rynkevic, Rita [1 ,2 ,6 ]
Mackova, Katerina [1 ,2 ,5 ]
Bosman, Anton W. [7 ]
Dankers, Patricia Y. W. [3 ,4 ]
Deprest, Jan [1 ,2 ,8 ]
机构
[1] Katholieke Univ Leuven, Ctr Surg Technol, Grp Biomed Sci, Leuven, Belgium
[2] Katholieke Univ Leuven, Dept Dev & Regenerat Woman & Child, Grp Biomed Sci, Leuven, Belgium
[3] Eindhoven Univ Technol, Inst Complex Mol Syst, POB 513, NL-5600 MB Eindhoven, Netherlands
[4] Eindhoven Univ Technol, Dept Biomed Engn, Lab Chem Biol, POB 513, NL-5600 MB Eindhoven, Netherlands
[5] Charles Univ Prague, Fac Med 3, Inst Care Mother & Child, Prague, Czech Republic
[6] Univ Porto, Fac Engn, INEGI, Porto, Portugal
[7] SupraPolix BV, Eindhoven, Netherlands
[8] Univ Hosp KU Leuven, Pelv Floor Unit, Leuven, Belgium
关键词
Immunomodulation; Supramolecular biomaterial; Neovascularization; Electrospun mesh; Pelvic floor; physiological compliance; PELVIC ORGAN PROLAPSE; MUSCLE REGENERATION; FIBROBLASTS; CELLS; SCAFFOLDS; HERNIA; ANGIOGENESIS; MYOGENESIS;
D O I
10.1016/j.actbio.2020.01.041
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Therefore, we aimed to develop a functionalized electrospun mesh that promotes tissue ingrowth and provides adequate mechanical strength and compliance during degradation. We describe the in vivo function of a new supramolecular bioactivated polycarbonate (PC) material based on fourfold hydrogen bonding ureidopyrimidinone (UPy) units (UPy-PC). The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Morphometric analysis of the musculofascial content during wound healing showed that cRGD functionalization promotes myogenesis with inhibition of collagen deposition at 14 days. It also prevents muscle atrophy at 90 days and exerts an immunomodulatory effect on infiltrating macrophages at 14 days and foreign body giant cell formation at 14 and 90 days. Additionally, the bioactivated material promotes neovascularization and connective tissue ingrowth. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in the rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. Our results provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP. Statement of Significance Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Ureidopyrimidinone-polycarbonate is a elastomeric and biodegradable electrospun mesh, which could mimic physiological compliance. The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. These data provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:82 / 91
页数:10
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