Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans

Abstract

Although regarded as a promising treatment for type 1 diabetes, clinical islet transplantation in the portal vein is still hindered by a low transplantation outcome. Alternative transplantation sites have been proposed, but the survival of extra-hepatically transplanted islets of Langerhans critically depends on quick revascularization after engraftment. This study aims at developing a new 3D scaffold platform that can actively boost vascularization and may find an application for extra-hepatic islet transplantation. The construct consists of a 3D ring-shaped polycaprolactone (PCL) scaffold with heparinized surface to electrostatically bind vascular endothelial growth factor (VEGF), surrounding a hydrogel core for islets encapsulation. Heparin immobilization improves the amount of VEGF retained by the construct, up to 3.6 fold, compared to untreated PCL scaffolds. In a chicken chorioallanthoic membrane model, VEGF immobilized on the construct enhances angiogenesis in close proximity and on the surface of the scaffolds. After 7 days, islets encapsulated in the alginate core show functional response to glucose stimuli comparable to free-floating islets. Thus, the developed platform has the potential to support rapid vascularization and islet endocrine function.

3D Printed Polycaprolactone Carbon Nanotube Composite Scaffolds for Cardiac Tissue Engineering

“…PCL nanocomposites (nanoclays, graphene, and CNTs) can be prepared using methods such as solvent casting, freeze drying, and electrospinning . However, these existing fabrication methods are unable to produce scaffolds of desired control pore sizes.…”

Tissue‐engineering approaches in pancreatic islet transplantation

“…Moreover, with the aim of “functionalizing” these synthetic scaffolds, that is, increasing their biocompatibility, they have been coupled with bioactive agents that increase the hydrophilicity of their surfaces (Liu, Holzwarth, & Ma, ). Thus, synthetic polymers combined with different biological materials (Brady et al, ; Brubaker, Kissler, Wang, Kaufman, & Messersmith, ; Liao et al, ; Marchioli et al, ) or with ECM proteins (Llacua et al, ; Salvay et al, ) have been successfully used in preclinical islet transplantation approaches.…”

Polymeric Scaffolds for Pancreatic Tissue Engineering: A Review

“…These cells showed better proliferation, attributed to the reduced caspase-3 expression, and improved cell survival [42]. [33] Increased release of acidic degradation products [33] Inflammatory response [33] Rapid in vivo absorption [33] PLA Biocompatible and biodegradable [101] Long half-life [101] Tailorable physico-chemical properties [103] Hydrophobic nature with low biomimetic and cell adhesion properties [102] PLGA High biocompatibility [108] Non-toxic biodegradation [108] Tunable mechanical strength [109] Biodegradation rate [109] Poor protein absorbance, cell affinity, and surface characters like hydrophilicity [110] PCL Biodegradable [16] Low melting point [118] Remarkable blend compatibility, versatile mechanical properties, and viscoelastic properties [118] Hydrophobic nature, limited bio-regulatory activity, and susceptible to bacteria-mediated degradation [33] PDMS High biocompatibility [125] Excellent oxygen solubility [125] Ideal for slow release of compounds [126] Hydrophobic surface, low cell adhesion [126] PEG Low immunogenicity, tissue-like elasticity, well-defined chemistry [130] Biologically inert, does not support cell growth [129] Legend: PCL -polycaprolactone, PDMS -polydimethylsiloxane, PEG -polyethylene glycol, PGA -polyglycolic acid, PLA -polylactic acid, PLGA -polylactic-co-glycolic acid.…”

“…The embedded islets were shown to maintain their viability and functionality, responding normally to glucose stimulations, and at the same time, possessing obvious immune protection properties. The scaffold demonstrated improved revascularization; it may thus be used as potential vessel for subcutaneous islet transplantation [118].…”

“…Since islets require a much greater blood supply than any other pancreatic cell compartment [137], the choice of transplantation site becomes important to allow the transplanted construct receiving sufficient blood supply for survival. Various sites for transplantation have been examined, including the peritoneal cavity [122], hepatic portal vein [118], subcutaneous space [65], and subcapsular space of the kidney [41,49]. Some sites such as omental pouch [76] and mesentery [137] have shown promising results, but the problem of hypoxia and shortage of blood supply is yet to be resolved.…”