A cell‐free approach with a supporting biomaterial in the form of dispersed microspheres induces hyaline cartilage formation in a rabbit knee model

Abstract

The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for the differentiation of the mesenchymal stem cells that migrate from the bone marrow. The possible inflammatory response to these biomaterials was previously studied by means of the culture of RAW264.7 macrophages. The microspheres were implanted in a 3 mm‐diameter defect in the trochlea of the femoral condyle of New Zealand rabbits, covering them with a poly(l‐lactic acid) (PLLA) membrane manufactured by electrospinning. Experimental groups included a group where exclusively PLLA microspheres were implanted, another group where a mixture of 50/50 microspheres of PLLA (hydrophobic and rigid) and others of chitosan (a hydrogel) were used, and a third group used as a control where no material was used and only the membrane was covering the defect. The histological characteristics of the regenerated tissue have been evaluated 3 months after the operation. We found that during the regeneration process the microspheres, and the membrane covering them, are displaced by the neoformed tissue in the regeneration space toward the subchondral bone region, leaving room for the formation of a tissue with the characteristics of hyaline cartilage.

Design and characterization of microspheres for a 3D mesenchymal stem cell culture

“…In a nutshell, microspheres are a promising cell culture tool with great potential in fields such as tissue engineering and cell therapy. Recently, our groups reported the development of a system for cartilage regeneration based on microspheres chitosan/poly(L-lactic acid) which create an adequate biomechanical environment for the differentiation of the MSCs migrating to the region of cartilage defect, after injuring subchondral bone in a rabbit knee model [Zurriaga Carda et al, 2019]. Three months after surgery, the histological characteristics of the regenerated tissue were found to be those of hyaline cartilage.…”

Mesenchymal Stem Cells Cultured in a 3D Microgel Environment Containing Platelet-Rich Plasma Significantly Modify Their Chondrogenesis-Related miRNA Expression

“…On the other hand, it allows mesenchymal cells to easily migrate from the subchondral bone if the implantation of the support material is combined with an injury to the subchondral bone with techniques such as microfracture. This strategy allowed the formation of a tissue with all the characteristics of hyaline cartilage in a rabbit knee model [23].…”

Stability of Biomimetically Functionalised Alginate Microspheres as 3D Support in Cell Cultures

“…The cells are seeded into the space between the microspheres, whose surface can be functionalised to provide cell adhesion sequences [ 14 , 15 , 16 ], while the microspheres themselves can support the release of growth factors during culture [ 17 , 18 ]. The same strategy can be used for in vivo tissue regeneration [ 19 ].…”