MULTIMATERIAL AND MULTISCALE SCAFFOLD FOR TENDON/LIGAMENT REGENERATION

Jun 30, 2022, 12:10 PM
10m
Room: S3 B

Room: S3 B

Speaker

Micalizzi, Simone (Research Center E. Piaggio and Dpt. of Information Engineering, University of Pisa )

Description

Tendon/ligament injuries are a relevant clinical problem in modern society. Although these tissues can selfheal when a lesion occurs, the complete functional recovery is difficult to achieve due to their low cellularity and vascularity. Moreover, reconstruction strategies have a non-negligible failure rate [1]. Failures often occur at the enthesis, the tendon/ligament-bone insertion [2]. This junction is a heterotypic tissue characterized by a graded structure from soft (ligament) to hard (bone) tissues with a heterogeneous distribution of cell types, matrix components and architecture [3]. In this work, a multimaterial and multiscale approach was developed, to fabricate scaffolds mimicking the complexity of these tissues, exploiting the combination of electrospinning and 3D printing technologies. Firstly, commercial, medical grade, and bioresorbable polymers both natural (porcine gelatin and gelatin methacryloyl(GelMA)) and synthetic (poly(l-lactic acid)(PLLA), poly(lactic-co-glycolic acid)(PLGA), polycaprolactone (PCL)) were systematically investigated to select the most valuable candidate. On supports made by solvent casting, we analyzed cell viability, proliferation, and gene expression of bone marrowderived mesenchymal stem cells (BM-MSCs). Among the tested materials, PLGA and PCL displayed the best ability to promote the proliferation of BM-MSCs. Further studies highlighted the ability of PLGA and PCL to promote, respectively, the tenogenic and osteogenic differentiation of BM-MSCs. Subsequently, a scaffold fabrication protocol was developed. For the region that interacts with bone, PCL grid-shaped scaffolds were 3D printed by fused deposition modelling (FDM) technology [4]. The ability of
these constructs to promote the BM-MSCs osteogenic differentiation was validated by confocal microscopy imaging. The tendon-like aligned fiber network was replicated by electrospinning PLGA fibers collected on a rotating drum collector. Electrospun structures were mechanically tested, and the fiber alignment was evaluated as function of drum revolutions per minute. Viability and proliferation tests highlighted the possibility to use these electrospun structures as scaffold for tendon/ligament engineering. The enthesis was replicated by directly extruding PCL onto PLGA electrospun films. A fine tuning of the extrusion parameters allowed the PCL deposition onto the electrospun PLGA mates without affecting the fibers integrity, as highlighted by scanning electron microscopy analysis. Scaffolds presenting the three different regions were, then, fabricated and the strength of the interface between 3D printed and electrospun structures was evaluated performing tensile tests. Finally, following this fabrication protocol bidimensional and 3D-dimensional anterior cruciate ligament (ACL) scaffolds, presenting the osteotendinous junction, were fabricated.

References
[1] Jason T. Shearn et al., Musculoskelet Neuronal Interact. 2011 Jun; 11(2): 163–173.
[2] Zhao S. et al., Colloids Surf., B Biointerfaces (2017): 157, 407.
[3] Hammoudi T M. et al., Biomaterials for Tissue Engineering Applications, Springer pp 307–41.
[4] G.Criscenti et al., Biofabrication, vol. 8, no. 1, p. 15009, 2016

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