Processing of Continuous Non‐Crosslinked Collagen Fibers for Microtissue Formation at the Muscle‐Tendon Interface

Abstract

One of the main components of the extracellular matrix (ECM) in natural tissues is collagen. Therefore, there has been a strong focus on processing of collagen for biomaterials application in tissue engineering such as in anisotropic tissues like muscles and tendons. To achieve native-like mechanical properties of the in vitro processed collagen, various crosslinking methods have been tested, but the used crosslinkers often do not yield sufficient mechanical properties or induce considerable inflammatory reactions. Here, good mechanical stability of collagen fibers is achieved by self-assembly during wet-spinning without the need of additional crosslinkers. The produced endless collagen fibers show fibril alignment within the fiber with a typical D-band pattern and a periodicity of approximately 67 nm, which is unique for fibril-forming collagens. Furthermore, the collagen fibers are processed into hierarchical assemblies using textile-engineering techniques. The woven assemblies are shown to be excellent substrates for the formation of muscle microtissue with long, aligned, and contractile myofibers. Such constructs are highly important at the muscle-tendon-junction (MTJ) and therefore myoblasts and fibroblasts are co-cultured to develop an MTJ-model.

One‐Step Bioprinting of Multi‐Channel Hydrogel Filaments Using Chaotic Advection: Fabrication of Pre‐Vascularized Muscle‐Like Tissues

“…[78,79] Cell lengths can be further increased to 500-600 μm by applying physical stimuli, such as uniaxial patterning, uniaxial stretching, or electric pulses. [79][80][81][82] In our experiments, no physical stimuli were required to induce similar cell lengths. We also quantified the number of nuclei per multinucleated cell in our actin/DAPI staining micrographs using image analysis.…”

Graphene Oxide–Protein-Based Scaffolds for Tissue Engineering: Recent Advances and Applications

“…Direct inter-chain hydrogen bonds connect these chains, limiting rotation and ensuring the stability of the triple-helix collagen [43]. Because collagen is the most abundant structural protein in vertebrates and plays important roles in controlling cell functions such as cell adhesion, proliferation, and differentiation, collagen-based biomaterials have been extensively used to prepare porous scaffolds for engineering tissue [44]. Furthermore, collagen type I-based biomaterials and fiber processing techniques have been employed to mimic the natural microstructure of various tissues; thus, porous collagen scaffolds are being used in the tissue engineering of cartilage, meniscus, bone, ligament, nerve, skin, and related structures [45,46].…”

A bioprinted complex tissue model for myotendinous junction with biochemical and biophysical cues

“…Generally, the approach to heal an MTJ defect has involved the use of sutures, but this method has a high recurrence rate and induces the formation of fibrous scar tissue in the defective region 8–10 . To overcome this problem, MTJ regeneration using tissue engineering strategies has been pursued as an alternative and, in particular, research using functional biomaterials with structurally and biochemically biomimetic properties in the tissues of muscles and tendons and their interfaces have been the subject of several studies 11–14 . Although significant progress has been made in MTJ regeneration through the use of biomaterials and printing technologies, engineered biomaterials showing the unique physical/biological characteristics of MTJ are still required to obtain a perfect junction structure.…”

“… 8 , 9 , 10 To overcome this problem, MTJ regeneration using tissue engineering strategies has been pursued as an alternative and, in particular, research using functional biomaterials with structurally and biochemically biomimetic properties in the tissues of muscles and tendons and their interfaces have been the subject of several studies. 11 , 12 , 13 , 14 Although significant progress has been made in MTJ regeneration through the use of biomaterials and printing technologies, engineered biomaterials showing the unique physical/biological characteristics of MTJ are still required to obtain a perfect junction structure. Furthermore, most of the research has been focused on biomaterials and processing techniques to regenerate muscle and tendon tissues, although the MTJ function is a critical component in force transmission through the muscle–tendon, much less research has been conducted on the regeneration of the muscle and tendon interface.…”