title: Multifunctional hydrogel-based scaffold for improving the functionality of encapsulated therapeutic cells and reducing inflammatory response.
abstract: Since the introduction of cell immunoisolation as an alternative to protect transplanted cells from host immune attack, much effort has been made to develop this technology into a realistic clinical proposal. Several promising approaches have been investigated to resolve the biotechnological and biosafety challenges related to cell microencapsulation. Here, a multifunctional hydrogel-based scaffold consisting of cell-loaded alginate-poly-l-lysine-alginate (APA) microcapsules and dexamethasone (DXM)-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres embedded in alginate hydrogel is developed and evaluated. Initially, the feasibility of using an alginate hydrogel for enclosing APA microcapsules was studied in a xenogeneic approach. In addition, the performance of the local release of DXM was addressed. The in vitro studies confirmed the correct adaptation of the enclosed cells to the scaffolds in terms of metabolic activity and viability. The posterior implantation of the hydrogel-based scaffolds containing cell-loaded microcapsules revealed that the hematocrit levels were maintained high and constant, and the pericapsular overgrowth was reduced in the DXM-treated rats for at least 2months. This multifunctional scaffold might have a synergistic effect: (1) providing a physical support for APA microcapsules, facilitating administration, ensuring retention and recuperation and preventing dissemination; and (2) reducing post-transplantation inflammation and foreign body reaction, thus prolonging the lifetime of the implant by the continuous and localized release of DXM.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Argia
authors.initials: A
authors.lastname: Acarregui
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Enara
authors.initials: E
authors.lastname: Herrán
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.affiliation: CIBER-BBN-Bioscaff Cartílago, INIBIC-Hospital Universitario A Coruña, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Blanco
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain. Electronic address: rosa.hernandez@ehu.es.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernandez
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D002214:Capsules / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D017690:Cell Transplantation; D018914:Cells, Immobilized / Q000378:metabolism / Q000637:transplantation; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D003907:Dexamethasone / Q000737:chemistry / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000464:Alginates; D000893:Anti-Inflammatory Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D020100:Hydrogels; C051546:alginate-polylysine-alginate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone
keywords: Alginate Hydrogel-based scaffolds; Cell encapsulation; Dexamethasone; Poly(lactic-co-glycolic) acid; Xenotransplantation