TY  - JOUR
A1  - Ouhaddi, Yassine
A1  - Charbonnier, Baptiste
A1  - Porge, Juliette
A1  - Zhang, Yu-Ling
A1  - Garcia, Isadora
A1  - Gbureck, Uwe
A1  - Grover, Liam
A1  - Gilardino, Mirko
A1  - Harvey, Edward
A1  - Makhoul, Nicholas
A1  - Barralet, Jake
T1  - Development of neovasculature in axially vascularized calcium phosphate cement scaffolds
JF  - Journal of Functional Biomaterials
N2  - Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical proof of concept for biomaterial-induced luminal sprouting of large-diameter vessels. In this study, we investigated if sprouting was a general response to surgical injury or placement of an inorganic construct around the vessel. Cylindrical biocement scaffolds of differing chemistries were placed around the femoral vein. A contrast agent was used to visualize vessel ingrowth into the scaffolds. Cell populations in the scaffold were mapped using immunohistochemistry. Calcium phosphate scaffolds induced 2.7–3 times greater volume of blood vessels than calcium sulphate or magnesium phosphate scaffolds. Macrophage and vSMC populations were identified that changed spatially and temporally within the scaffold during implantation. NLRP3 inflammasome activation peaked at weeks 2 and 4 and then declined; however, IL-1β expression was sustained over the course of the experiment. IL-8, a promoter of angiogenesis, was also detected, and together, these responses suggest a role of sterile inflammation. Unexpectedly, the effect was distinct from an injury response as a result of surgical placement and also was not simply a foreign body reaction as a result of placing a rigid bioceramic next to a vein, since, while the materials tested had similar microstructures, only the calcium phosphates tested elicited an angiogenic response. This finding then reveals a potential path towards a new strategy for creating better pro-regenerative biomaterials.
KW  - angiogenesis
KW  - axial vascularization
KW  - bioceramic
KW  - bioinorganic
KW  - calcium phosphate
KW  - NLRP3
KW  - inflammation
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304026
SN  - 2079-4983
VL  - 14
IS  - 2
ER  -