3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration

被引：161

作者：

Freeman, Fiona E. ^{[1
,2
]}

Pitacco, Pierluca ^{[1
,2
]}

van Dommelen, Lieke H. A. ^{[3
]}

Nulty, Jessica ^{[1
,2
]}

Browe, David C. ^{[1
,2
]}

Shin, Jung-Youn ^{[4
,5
]}

Alsberg, Eben ^{[4
,5
,6
,7
,8
,9
]}

Kelly, Daniel J. ^{[1
,2
,10
,11
,12
]}

机构：

[1] Trinity Coll Dublin, Trinity Ctr Biomed Engn, Trinity Biomed Sci Inst, Dublin, Ireland

[2] Trinity Coll Dublin, Sch Engn, Dept Mech & Mfg Engn, Dublin, Ireland

[3] Eindhoven Univ Technol, Dept Biomed Engn, Orthopaed Biomech, POB 513, NL-5600 MB Eindhoven, Netherlands

[4] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA

[5] Case Western Reserve Univ, Dept Orthopaed Surg, Cleveland, OH 44106 USA

[6] Univ Illinois, Dept Biomed Engn, Chicago, IL 60607 USA

[7] Univ Illinois, Dept Pharmacol, Chicago, IL 60607 USA

[8] Univ Illinois, Dept Orthopaed, Chicago, IL 60607 USA

[9] Univ Illinois, Dept Mech & Ind Engn, Chicago, IL 60607 USA

[10] Royal Coll Surgeons Ireland, Dept Anat, Dublin, Ireland

[11] Royal Coll Surgeons Ireland, Adv Mat & Bioengn Res Ctr AMBER, Dublin, Ireland

[12] Trinity Coll Dublin, Dublin, Ireland

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 33期

基金：

欧洲研究理事会;

关键词：

BONE MORPHOGENETIC PROTEIN-2; ENDOTHELIAL-CELLS; FUNCTIONAL REPAIR; FACTOR DELIVERY; VEGF; ANGIOGENESIS; RELEASE; BMP-2; OSTEOGENESIS; SYSTEM;

D O I：

10.1126/sciadv.abb5093

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.

引用

页数：15

共 48 条

[41] Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion [J].