Page 304 - IJB-9-5

International Journal of Bioprinting

RESEARCH ARTICLE
Multimaterial and multiscale scaffold for

engineering enthesis organ

Simone Micalizzi , Lara Russo , Chiara Giacomelli , Francesca Montemurro ,
1†
2†
2
1
Carmelo de Maria , Martina Nencioni , Laura Marchetti ,
2
2
1
Maria Letizia Trincavelli , Giovanni Vozzi 1*
2
1 Research Centre E. Piaggio and Department of Information Engineering, University of Pisa,
Largo L. Lazzarino 1, 56126 Pisa, Italy
2 Department of Pharmacy, University of Pisa, Pisa 56127, Italy
(This article belongs to the Special Issue: Bioprinting-based strategies for regenerative medicine, drug develop-
ment and food technology applications)
Abstract
Tendon and ligament injuries are relevant clinical problems in modern society, and the
current medical approaches do not guarantee complete recovery of the physiological
functionalities. Moreover, they present a non-negligible failure rate after surgery.
Failures often occur at the enthesis, which is the area of tendons and ligaments
insertion to bones. This area is highly anisotropic and composed of four distinct
zones: tendon or ligament, non-mineralized fibrocartilage, mineralized fibrocartilage,
and bone. The organization of these regions provides a gradient in mechanical
properties, biochemical composition, cellular phenotype, and extracellular matrix
organization. Tissue engineering represents an alternative to traditional medical
† These authors contributed equally approaches. This work presents a novel biofabrication approach for engineering the
to this work.
enthesis. Gradient-based scaffolds were fabricated by exploiting the combination of
*Corresponding author: electrospinning and three-dimensional (3D) bioprinting technologies. Studies were
Giovanni Vozzi
(giovanni.vozzi@unipi.it) conducted to evaluate scaffold biocompatibility by seeding bone marrow-derived
mesenchymal stem cells (BM-MSCs). Then, the scaffold’s ability to promote cellular
Citation: Micalizzi S, Russo L,
Giacomelli C, et al., 2023, adhesion, growth, proliferation, and differentiation in both tenogenic and osteogenic
Multimaterial and multiscale scaffold phenotypes was evaluated. Fabricated scaffolds were also morphologically and
for engineering enthesis organ. mechanically characterized, showing optimal properties comparable to literature
Int J Bioprint, 9(5): 763.
https://doi.org/10.18063/ijb.763 data. The versatility and potentiality of this novel biofabrication approach were
demonstrated by fabricating clinical-size 3D enthesis scaffolds. The mechanical
Received: February 19, 2023 characterization highlighted their behavior during a tensile test was comparable to
Accepted: April 24, 2023
Published Online: May 29, 2023 tendons and ligaments in vivo.
Copyright: © 2023 Author(s).
This is an Open Access article Keywords: Enthesis; Multiscale and multimaterial 3D bioprinting; Electrospinning;
distributed under the terms of the
Creative Commons Attribution Gradient scaffold; Human mesenchymal stem cells
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited. 1. Introduction
Publisher’s Note: Whioce
Publishing remains neutral with The musculoskeletal system plays a key role in maintaining the stability of the human body,
regard to jurisdictional claims in providing shape and support during locomotion. It is composed of two main systems: (i)
published maps and institutional
affiliations. the muscular system, including muscles attached to bones through tendons, and (ii) the

Volume 9 Issue 5 (2023) 296 https://doi.org/10.18063/ijb.763