TY - JOUR
T1 - L-DOPA as a small molecule surrogate to promote angiogenesis and prevent dexamethasone-induced ischemia
AU - Price, Claire F.
AU - Burgess, Diane J.
AU - Kastellorizios, Michail
N1 - Funding Information:
This research has been funded by a University of Connecticut Office of Undergraduate Research Supply Award and the US Army Medical Research and Materiel Command, Telemedicine & Advanced Technology Research Center , award W81XWH-09-1-0711 .
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/8/10
Y1 - 2016/8/10
N2 - The foreign body response to implantable biosensors has been successfully countered through the use of corticosteroids, such as dexamethasone. However, while controlling inflammation, dexamethasone also decreases angiogenesis, which may lead to delayed analyte readings. The concurrent application of VEGF with dexamethasone increases angiogenesis, but VEGF has physical stability issues and is not cost-effective. The use of l-DOPA, a small molecule drug shown to up-regulate VEGF in the Parkinsonian brain, can potentially resolve these issues by substituting for VEGF. In this work, l-DOPA was used for the first time as a pro-angiogenic agent to counteract dexamethasone-induced ischemia. Angiogenesis was modeled using the CAM assay and changes in blood vessel formation were recorded with both manual and digital techniques. As expected, dexamethasone reduced blood vessel formation in the CAM. Application of l-DOPA, on the other hand, increased blood vessel formation when dexamethasone and l-DOPA were administered simultaneously. This novel finding suggests the utility of l-DOPA in the field of implantable medical devices, such as biosensors, as well as tissue engineering applications where both a vascularized tissue environment and control of tissue response is desired.
AB - The foreign body response to implantable biosensors has been successfully countered through the use of corticosteroids, such as dexamethasone. However, while controlling inflammation, dexamethasone also decreases angiogenesis, which may lead to delayed analyte readings. The concurrent application of VEGF with dexamethasone increases angiogenesis, but VEGF has physical stability issues and is not cost-effective. The use of l-DOPA, a small molecule drug shown to up-regulate VEGF in the Parkinsonian brain, can potentially resolve these issues by substituting for VEGF. In this work, l-DOPA was used for the first time as a pro-angiogenic agent to counteract dexamethasone-induced ischemia. Angiogenesis was modeled using the CAM assay and changes in blood vessel formation were recorded with both manual and digital techniques. As expected, dexamethasone reduced blood vessel formation in the CAM. Application of l-DOPA, on the other hand, increased blood vessel formation when dexamethasone and l-DOPA were administered simultaneously. This novel finding suggests the utility of l-DOPA in the field of implantable medical devices, such as biosensors, as well as tissue engineering applications where both a vascularized tissue environment and control of tissue response is desired.
KW - Angiogenesis
KW - Biosensors
KW - CAM assay
KW - Dexamethasone
KW - l-DOPA
UR - http://www.scopus.com/inward/record.url?scp=84974701549&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.05.065
DO - 10.1016/j.jconrel.2016.05.065
M3 - Article
C2 - 27261334
AN - SCOPUS:84974701549
SN - 0168-3659
VL - 235
SP - 176
EP - 181
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -