Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: from fabrication to preclinical validation.
Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane angiogenesis model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine.
Mondalek
Fadee G
FG
Department of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, Oklahoma 73019, USA.
Ashley
Richard A
RA
Roth
Christopher C
CC
Kibar
Yusuf
Y
Shakir
Nabeel
N
Ihnat
Michael A
MA
Fung
Kar-Ming
KM
Grady
Brian P
BP
Kropp
Bradley P
BP
Lin
Hsueh-Kung
HK
D000818:Animals; D002642:Chick Embryo; D004285:Dogs; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012038:Regeneration / Q000502:physiology; D013552:Swine; D001743:Urinary Bladder / Q000473:pathology / Q000502:physiology
D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid