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International Journal of Bioprinting Biomimetic scaffolds for tendon healing

1. Introduction Regarding the materials used in extrusion-based 3D
bioprinting, hydrogels are postulated as good candidates
The global prevalence of musculoskeletal disorders is on for the regeneration of partial tendon tears. These 3D
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the rise, representing a substantial burden for healthcare networks are formed by biopolymers capable of retaining
systems. They compromise more than 150 diverse diseases a large amount of water in their structure. Besides, they
1,2
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that affect joints, bones, muscles, and connective tissues. are highly biocompatible, reducing the risk of adverse
3,4
Included among them are tendon injuries, which can be responses once implanted in the body. Nonetheless, until
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affected by different pathologies. One of these pathologies now, the hydrogels developed for 3D bioprinting applied
is tendon rupture, which can be classified into partial to tissue regeneration suffer from several limitations. On
tears (depending on the area of the tendon that is affected: the one hand, the mechanical properties of these hydrogels
minor 25%, moderate or severe 75%) and complete tears. do not meet the minimum requirements for being used
5
Although much emphasis is placed on complete injuries, it in 3D bioprinting. This can be attributed to the very low
is of paramount importance to recall that partial injuries viscosities they exhibit in some cases, and the limitations
are very common and are equally limiting and painful for in obtaining good shape fidelity or reproducibility in other
patients. The current principal treatment for tendon partial cases. 20,21 On the other hand, under most circumstances,
ruptures consists of surgery and rehabilitation for severe the composition of the hydrogel, although biocompatible,
cases, and immobilization and repose for minor cases. is sparingly biomimetic, as it is usually composed of
6
In a very significant number of cases, regeneration results only one or two molecules/macromolecules, with their
in fibrotic tissue with poor mechanical properties, which concentrations being highly different from those in the
hampers its function and limits patients’ life quality. ECM. These factors lead to reduced effectiveness of
7,8
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With the advent of tissue engineering, an enormous field of the scaffolds. Consequently, the development of a 3D
possibilities has opened up to address this medical problem hydrogel-based structure, with controlled structural and
by utilizing different complex approaches. Nevertheless, mechanical properties, that allows improving tendon
9,10
the strategies carried out to date in tissue engineering tissue regeneration through complex and biomimetic
are still too technically simple and mainly based on the approaches, remains a hurdle to be overcome.
study of various elements independently. In this sense,
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despite the significant progress, the successful fabrication Growth factors are frequently used in the regeneration
of composite structures that combine different elements of damaged tissues. 23,24 They have generally been dosed
and allow the regeneration of partial damages in complex directly through injections at the injured site, 25,26 generating
tissues, such as tendons, remains a considerable challenge. excellent outcomes, despite some shortcomings such as the
non-specific diffusion of molecules to other locations in the
To address this issue, extrusion three-dimensional organism and the rapid degradation. 27,28 Multiple growth
(3D) bioprinting emerged as a promising and powerful factors have been utilized in the case of tendon being the
technique for the development of highly complex scaffolds target tissue; for instance, transforming growth factor-beta
and tissue constructs suitable for the regeneration of (TGF-β), platelet-derived growth factor (PDGF), vascular
partial tendon ruptures. This technology makes it endothelial growth factor (VEGF), basic fibroblast growth
12
possible to combine semisolid, hydrogel-like materials, factor (bFGF or FGF-2), insulin-like growth factor-1 (IGF-
cells, and molecules with different designs, morphologies, 1), and connective tissue growth factor (CTGF) are some
and dimensions. 13,14 According to the ASTM standards and of the previously tested growth factors. 29-33 Among them,
the physicochemical properties of the materials to be used VEGF and PDGF should be highlighted. First, VEGF
(semisolid, hydrogel-like), the air-flow material extrusion favors the formation of new blood vessels, allowing a
3D bioprinting is the most convenient for the purposes greater amount of nutrients and oxygen to reach the cells
of this study. Although this technique is being used to (necessary considering that collagen synthesis is an oxygen-
15
develop scaffolds and tissue constructs for total tendon dependent process). 34,35 Meanwhile, PDGF promotes cell
ruptures (mainly using synthetic materials), it can also be proliferation and migration, favoring the migration of
36
adjusted for addressing partial ruptures. In this study, the stem cells to the damaged tendon and the proliferation of
16
objective is not to provide complete mechanical support tenocytes and tenoblasts. Given their proven effectiveness,
but to promote rapid regeneration of extracellular matrix the incorporation of these molecules into 3D-bioprinted
(ECM) to recover the lost functionality of the tendon structures seems reasonable, giving rise to much more
tissue. Potential strategies to achieve this purpose include complex approaches that allow better regeneration of
the modification of the components that are used during partial tendon injuries. Furthermore, this would reduce
3D bioprinting, such as the type of materials and/or the use the diffusion limitation of the factors since they would be
of growth factors. kept at the exact location where they are needed (where the
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Volume 10 Issue 3 (2024) 443 doi: 10.36922/ijb.2632