Abstract
Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.
Highlights
Musculoskeletal conditions have been considered the most prevalent occupational diseases and lead to costs in medical care and social assistance with an estimated economic burden of 37 billion euros to European national health systems [1,2]
RePsuorltosus composite supports were obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the 3p.r1e.sPernecpearoaftiPoLnGofAt,haenPdoroosutseoCcoomnpdousictteivSeupapgoernttSs,cai.fefo.,ldβ-TCP and strontium folate (SrFO)
The HAMA hydrogel was capable of swelling under hydration conditions, but it reached the collapse of the structure in a dry environment (Figure 3A)
Summary
Musculoskeletal conditions have been considered the most prevalent occupational diseases and lead to costs in medical care and social assistance with an estimated economic burden of 37 billion euros to European national health systems [1,2]. Current treatments for damaged articular cartilage do not represent a cure for the pathology because they only delay its progress, or they involve the creation of new defects with the possibility of increasing morbidity of the donor tissue as an adaptive immune response, as well as the creation of a focus of infections [5]. To avoid these adverse effects, regenerative therapies based on tissue engineering are becoming the most favourable and promising alternative for the regeneration of the osteochondral tissue. These new therapies combine the administration of cells, signalling molecules, and polymeric scaffolds [6]
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