Potential of Graphene–Polymer Composites for Ligament and Tendon Repair: A Review

Abstract

Tendon/ligament injuries are debilitating conditions that affect the life quality of a great percentage of the adult population. Several challenges still have to be addressed regarding the repair of these tissues, as current treatments show limited success. The use of biocompatible and biodegradable polymeric scaffolds potentially helps accomplish a complete and long‐term functional repair but, unfortunately, these materials lack adequate mechanical properties to be used in such demanding applications. Graphene is a subject of interest for tissue‐repair applications due to its electrical conductivity and mechanical properties. If incorporated adequately, it may significantly improve the physical properties of the composite, even at small loadings. Furthermore, graphene presents a biocompatible surface that may enhance cell adhesion, proliferation and differentiation and demonstrates promising outcomes in several in vitro and in vivo biological applications. Therefore, herein, the potential of graphene materials for the reinforcement of biodegradable polymers of interest for tendon/ligament repair is explored. The effect of graphene on relevant features such as mechanical properties, biodegradability, and biocompatibility is revised, to understand the feasibility of these composites to fulfill the requirements associated with these tissues and conclude how their applicability is extended to this field.

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites

“…The release of bFGF stimulated cell proliferation and the gene expression of tendon/ligament-specific ECM proteins increased the collagen production and, hence, the mechanical properties of the scaffold [ 50 ]. Despite the significant advancements in the tendon/ligament TE, the current solutions have not yet reached the clinic or even the pre-clinic due to some drawbacks in the application including poor mechanical strength and quick degradability or insufficient biological activity [ 7 ]. Another remaining problem is the lack of reproducibility and ability to precisely control the pore size and interconnectivity, as well as the scaffolds’ structure and mechanical properties [ 47 ].…”

“…The obtained images illustrate a homogenous dispersion of EGs after 3D printing. When well dispersed, the large surface area of EGs maximizes the interfacial area, which results in an enhanced load transfer ability [ 7 ]. The smoothness of the external surface can also be observed, the composite scaffolds showing a slightly rougher surface due to the EG nanoparticles.…”

“…For all formulations, the storage modulus slightly increased while the tan δ decreased with increasing frequency, as commonly observed in viscoelastic materials [ 54 , 55 ]. This viscoelastic characteristic was extremely important since native tendons and ligaments also exhibited viscoelastic behavior [ 7 ]. No significant differences were found for the damping ability between the PLA and composite scaffolds.…”

“…A biodegradable scaffold should preserve at least half of its structural and mechanical integrity for a minimum of 3–6 months (for tendon/ligament recovery) and then should degrade gradually [ 7 ]. Approximately 6 weeks after the initial injury, remodeling begins and will eventually yield a slightly disorganized ECM [ 10 ].…”

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites

“…The release of bFGF stimulated cell proliferation and the gene expression of tendon/ligament-specific ECM proteins increased the collagen production and, hence, the mechanical properties of the scaffold [ 50 ]. Despite the significant advancements in the tendon/ligament TE, the current solutions have not yet reached the clinic or even the pre-clinic due to some drawbacks in the application including poor mechanical strength and quick degradability or insufficient biological activity [ 7 ]. Another remaining problem is the lack of reproducibility and ability to precisely control the pore size and interconnectivity, as well as the scaffolds’ structure and mechanical properties [ 47 ].…”

“…The obtained images illustrate a homogenous dispersion of EGs after 3D printing. When well dispersed, the large surface area of EGs maximizes the interfacial area, which results in an enhanced load transfer ability [ 7 ]. The smoothness of the external surface can also be observed, the composite scaffolds showing a slightly rougher surface due to the EG nanoparticles.…”

“…For all formulations, the storage modulus slightly increased while the tan δ decreased with increasing frequency, as commonly observed in viscoelastic materials [ 54 , 55 ]. This viscoelastic characteristic was extremely important since native tendons and ligaments also exhibited viscoelastic behavior [ 7 ]. No significant differences were found for the damping ability between the PLA and composite scaffolds.…”

“…A biodegradable scaffold should preserve at least half of its structural and mechanical integrity for a minimum of 3–6 months (for tendon/ligament recovery) and then should degrade gradually [ 7 ]. Approximately 6 weeks after the initial injury, remodeling begins and will eventually yield a slightly disorganized ECM [ 10 ].…”

Engineering Ligament Scaffolds Based on PLA/Graphite Nanoplatelet Composites by 3D Printing or Braiding

“…The ACL is formed by two anatomical bands (anteromedial (AMB) and posterolateral (PLB) bands). Tensile tests of porcine ACL bundles, similar to human ACL, showed that the stiffness of Several studies have reported the mechanical improvement of PLA reinforced with graphene-based materials under static loading [42]. The mechanical response of knee ligaments, namely ACL, posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL) under static loading is also well documented [13,27].…”

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites

“…The release of bFGF stimulated cell proliferation and the gene expression of tendon/ligament-specific ECM proteins increased the collagen production and, hence, the mechanical properties of the scaffold [ 50 ]. Despite the significant advancements in the tendon/ligament TE, the current solutions have not yet reached the clinic or even the pre-clinic due to some drawbacks in the application including poor mechanical strength and quick degradability or insufficient biological activity [ 7 ]. Another remaining problem is the lack of reproducibility and ability to precisely control the pore size and interconnectivity, as well as the scaffolds’ structure and mechanical properties [ 47 ].…”

“…The obtained images illustrate a homogenous dispersion of EGs after 3D printing. When well dispersed, the large surface area of EGs maximizes the interfacial area, which results in an enhanced load transfer ability [ 7 ]. The smoothness of the external surface can also be observed, the composite scaffolds showing a slightly rougher surface due to the EG nanoparticles.…”

“…For all formulations, the storage modulus slightly increased while the tan δ decreased with increasing frequency, as commonly observed in viscoelastic materials [ 54 , 55 ]. This viscoelastic characteristic was extremely important since native tendons and ligaments also exhibited viscoelastic behavior [ 7 ]. No significant differences were found for the damping ability between the PLA and composite scaffolds.…”

“…A biodegradable scaffold should preserve at least half of its structural and mechanical integrity for a minimum of 3–6 months (for tendon/ligament recovery) and then should degrade gradually [ 7 ]. Approximately 6 weeks after the initial injury, remodeling begins and will eventually yield a slightly disorganized ECM [ 10 ].…”

Engineering Ligament Scaffolds Based on PLA/Graphite Nanoplatelet Composites by 3D Printing or Braiding

“…The ACL is formed by two anatomical bands (anteromedial (AMB) and posterolateral (PLB) bands). Tensile tests of porcine ACL bundles, similar to human ACL, showed that the stiffness of Several studies have reported the mechanical improvement of PLA reinforced with graphene-based materials under static loading [42]. The mechanical response of knee ligaments, namely ACL, posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL) under static loading is also well documented [13,27].…”

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites

“…The release of bFGF stimulated cell proliferation and the gene expression of tendon/ligament-specific ECM proteins increased the collagen production and, hence, the mechanical properties of the scaffold [ 50 ]. Despite the significant advancements in the tendon/ligament TE, the current solutions have not yet reached the clinic or even the pre-clinic due to some drawbacks in the application including poor mechanical strength and quick degradability or insufficient biological activity [ 7 ]. Another remaining problem is the lack of reproducibility and ability to precisely control the pore size and interconnectivity, as well as the scaffolds’ structure and mechanical properties [ 47 ].…”

“…The obtained images illustrate a homogenous dispersion of EGs after 3D printing. When well dispersed, the large surface area of EGs maximizes the interfacial area, which results in an enhanced load transfer ability [ 7 ]. The smoothness of the external surface can also be observed, the composite scaffolds showing a slightly rougher surface due to the EG nanoparticles.…”

“…For all formulations, the storage modulus slightly increased while the tan δ decreased with increasing frequency, as commonly observed in viscoelastic materials [ 54 , 55 ]. This viscoelastic characteristic was extremely important since native tendons and ligaments also exhibited viscoelastic behavior [ 7 ]. No significant differences were found for the damping ability between the PLA and composite scaffolds.…”

“…A biodegradable scaffold should preserve at least half of its structural and mechanical integrity for a minimum of 3–6 months (for tendon/ligament recovery) and then should degrade gradually [ 7 ]. Approximately 6 weeks after the initial injury, remodeling begins and will eventually yield a slightly disorganized ECM [ 10 ].…”

Engineering Ligament Scaffolds Based on PLA/Graphite Nanoplatelet Composites by 3D Printing or Braiding

“…The ACL is formed by two anatomical bands (anteromedial (AMB) and posterolateral (PLB) bands). Tensile tests of porcine ACL bundles, similar to human ACL, showed that the stiffness of Several studies have reported the mechanical improvement of PLA reinforced with graphene-based materials under static loading [42]. The mechanical response of knee ligaments, namely ACL, posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL) under static loading is also well documented [13,27].…”