Magnetic Nanoparticles for Efficient Delivery of Growth Factors: Stimulation of Peripheral Nerve Regeneration.
The only clinically approved alternative to autografts for treating large peripheral nerve injuries is the use of synthetic nerve guidance conduits (NGCs), which provide physical guidance to the regenerating stump and limit scar tissue infiltration at the injury site. Several lines of evidence suggest that a potential future strategy is to combine NGCs with cellular or molecular therapies to deliver growth factors that sustain the regeneration process. However, growth factors are expensive and have a very short half-life; thus, the combination approach has not been successful. In the present paper, we proposed the immobilization of growth factors (GFs) on magnetic nanoparticles (MNPs) for the time- and space-controlled release of GFs inside the NGC. We tested the particles in a rat model of a peripheral nerve lesion. Our results revealed that the injection of a cocktail of MNPs functionalized with nerve growth factor (NGF) and with vascular endothelial growth factor (VEGF) strongly accelerate the regeneration process and the recovery of motor function compared to that obtained using the free factors. Additionally, we found that injecting MNPs in the NGC is safe and does not impair the regeneration process, and the MNPs remain in the conduit for weeks.
Department of Biology, Università di Pisa, S.S. 12 Abetone e Brennero 4, 56127, Pisa, Italy.
Martina
M
Giannaccini
Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Mariano Esquillor, 50018, Zaragoza, Spain.
M Pilar
MP
Calatayud
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Andrea
A
Poggetti
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Silvia
S
Corbianco
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Michela
M
Novelli
Institute of Life Science, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy.
Melania
M
Paoli
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Pietro
P
Battistini
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Maura
M
Castagna
Department of Biology, Università di Pisa, S.S. 12 Abetone e Brennero 4, 56127, Pisa, Italy.
Luciana
L
Dente
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Paolo
P
Parchi
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Michele
M
Lisanti
Department of Translational Research and of New Surgical and Medical Technologies, Università di Pisa, Via Savi 8, 56126, Pisa, Italy.
Gabriella
G
Cavallini
Institute for Health Research Aragon IIS, Faculty of Medicine, C/Domingo Mirals/n, 50009, Zaragoza, Spain.
Concepción
C
Junquera
Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Mariano Esquillor, 50018, Zaragoza, Spain.
Gerardo F
GF
Goya
Department of Biology, Università di Pisa, S.S. 12 Abetone e Brennero 4, 56127, Pisa, Italy.|Institute of Life Science, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy.
Vittoria
V
Raffa
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D020932:Nerve Growth Factor / Q000737:chemistry / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D016716:PC12 Cells; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology
D058185:Magnetite Nanoparticles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020932:Nerve Growth Factor
delivery of growth factors; functional recovery; nanoparticle; nerve injury; nerve regeneration