title: Orthopedic bioactive implants: Hydrogel enrichment of macroporous titanium for the delivery of mesenchymal stem cells and strontium.
abstract: Insufficient implant stability is an important determinant in the failure of cementless prostheses. To improve osseointegration, we aim at generating a bioactive implant combining a macroporous titanium (TT) with a biocompatible hydrogel to encapsulate osteo-inductive factors and osteoprogenitor cells. Amidation and cross-linking degree of an amidated carboxymethylcellulose hydrogel (CMCA) were characterized by FT-IR spectrometry and mechanical testing. Bone marrow mesenchymal stem cells (BMSCs) from osteoarthritic patients were cultured on CMCA hydrogels, TT, and TT loaded with CMCA (TT + CMCA) with an optimized concentration of SrCl2 to evaluate cell viability and osteo-differentiation. Amidation and cross-linking degree were homogeneous among independent CMCA batches. SrCl2 at 5 μg/mL significantly improved BMSCs osteo-differentiation increasing calcified matrix (P < 0.01), type I collagen expression (P < 0.05) and alkaline phosphatase activity. TT + CMCA samples better retained cells into the TT mesh, significantly improving cell seeding efficiency with respect to TT (P < 0.05). BMSCs on TT + CMCA underwent a more efficient osteo-differentiation with higher alkaline phosphatase (P < 0.05) and calcium levels compared to cells on TT. Based on these in vitro results, we envision the association of TT with strontium-enriched CMCA and BMSCs as a promising strategy to generate bioactive implants promoting bone neoformation at the implant site.
authors.affiliation: Cell and Tissue Engineering Laboratory, Gruppo Ospedaliero San Donato Foundation, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lopa
authors.forename: David
authors.initials: D
authors.lastname: Mercuri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Colombini
authors.forename: Gennyfer
authors.initials: G
authors.lastname: De Conti
authors.forename: Francesco
authors.initials: F
authors.lastname: Segatti
authors.forename: Luigi
authors.initials: L
authors.lastname: Zagra
authors.forename: Matteo
authors.initials: M
authors.lastname: Moretti
mesh_terms: D000577:Amides / Q000737:chemistry; D001672:Biocompatible Materials / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D009985:Orthopedics; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D019736:Prostheses and Implants; D015203:Reproducibility of Results; D013324:Strontium / Q000494:pharmacology*; D014025:Titanium / Q000494:pharmacology*
chemical_list: D000577:Amides; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D014025:Titanium; D002266:Carboxymethylcellulose Sodium; D013324:Strontium
keywords: hydrogel; mesenchymal stem cells; osseointegration; strontium; titanium implant