Injectable xyloglucan hydrogels incorporating spheroids of adipose stem cells for bone and cartilage regeneration

• Published in: Materials Science & Engineering C Vol. 131; p. 112545
• Main Authors: Muscolino, Emanuela, Di Stefano, Anna Barbara, Trapani, Marco, Sabatino, Maria Antonietta, Giacomazza, Daniela, Moschella, Francesco, Cordova, Adriana, Toia, Francesca, Dispenza, Clelia
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01.12.2021; Elsevier BV
• Subjects: Biomedical materials; Bone growth; Cartilage; Cell differentiation; Cell proliferation; Cell spreading; Cell viability; Chondroblastic differentiation; Chondrocytes; Chondrogenesis; Differentiation; Dispersions; Gene expression; Hydrogels; Injectable hydrogels; Injection; Materials science; Mechanical properties; Mesenchyme; Osteogenesis; Osteogenic differentiation; Polymers; Regeneration; Regeneration (physiology); Spheroids; Spheroids of adipose stem cells; Stem cells; Xyloglucan; Spheroids of adipose stem cells; Xyloglucan; Injectable hydrogels; Osteogenic differentiation; Chondroblastic differentiation
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2021.112545

Cartilage or bone regeneration approaches based on the direct injection of mesenchymal stem cells (MSCs) at the lesion site encounter several challenges, related to uncontrolled cell spreading and differentiation, reduced cell viability and poor engrafting. This work presents a simple and versatile strategy based on the synergic combination of in-situ forming hydrogels and spheroids of adipose stem cells (SASCs) with great potential for minimally invasive regenerative interventions aimed to threat bone and cartilage defects. Aqueous dispersions of partially degalactosylated xyloglucan (dXG) are mixed with SASCs derived from liposuction and either a chondroinductive or an osteoinductive medium. The dispersions rapidly set into hydrogels when temperature is brought to 37 °C. The physico-chemical and mechanical properties of the hydrogels are controlled by polymer concentration. The hydrogels, during 21 day incubation at 37 °C, undergo significant structural rearrangements that support cell proliferation and spreading. In formulations containing 1%w dXG cell viability increases up to 300% for SASCs-derived osteoblasts and up to 1000% for SASCs-derived chondrocytes if compared with control 2D cultures. The successful differentiation into the target cells is supported by the expression of lineage-specific genes. Cell-cell and cell-matrix interactions are also investigated. All formulations resulted injectable, and the incorporated cells are fully viable after injection. [Display omitted] •Partially degalactosilated xyloglucan (dXG) dispersed in inductive media rapidly set into gels at 37°C•The physical networks undergo significant reorganization during incubation for 21 days•Gels provide control of stem cell differentiation towards a single cell lineage•1%w dXG gels show 300% viability for osteocytes and 1000% in chondrocytes after 21 days.•Cells mixed with the gels and injected through small gauge syringe needles retain viability