title: New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells.
abstract: The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair.
authors: LUNAM Université, Micro et Nanomédecines Biomimétiques-MINT, F-49933 Angers, France.
authors: Marie
authors: M
authors: Morille
authors: Tran
authors: T
authors: Van-Thanh
authors: Xavier
authors: X
authors: Garric
authors: Jérôme
authors: J
authors: Cayon
authors: Jean
authors: J
authors: Coudane
authors: Danièle
authors: D
authors: Noël
authors: Marie-Claire
authors: MC
authors: Venier-Julienne
authors: Claudia N
authors: CN
authors: Montero-Menei
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009113:Muramidase / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D053782:Transforming Growth Factor beta3; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase; D009113:Muramidase