Modifying the strength and strain concentration profile within collagen scaffolds using customizable arrays of poly-lactic acid fibers

Abstract

The tendon-to-bone junction is a highly specialized tissue which dissipates stress concentrations between mechanically dissimilar tendon and bone. Upon injury, the local heterogeneities across this insertion are not regenerated, leading to poor functional outcomes such as formation of scar tissue at the insertion and re-failure rates exceeding 90%. Although current tissue engineering methods are moving towards the development of spatially-graded biomaterials to begin to address these injuries, significant opportunities remain to engineer the often complex local mechanical behavior of such biomaterials to enhance their bioactivity. Here, we describe the use of three-dimensional printing techniques to create customizable arrays of poly-lactic acid (PLA) fibers that can be incorporated into a collagen scaffold under development for tendon bone junction repair. Notably, we use additive manufacturing concepts to generate arrays of spatially-graded fibers from biodegradable PLA that are incorporated into collagen scaffolds to create a collagen-PLA composite. We demonstrate the ability to tune the mechanical performance of the fiber-scaffold composite at the bulk scale. We also demonstrate the incorporation of spatially-heterogeneous fiber designs to establish non-uniform local mechanical performance of the composite biomaterial under tensile load, a critical element in the design of multi-compartment biomaterials for tendon-to-bone regeneration applications. Together, this work highlights the capacity to use multi-scale composite biomaterials to control local and bulk mechanical properties, and provides key insights into design elements under consideration for mechanically competent, multi-tissue regeneration platforms.

Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds

“…While promising, these initial findings suggested the need to improve the structural mechanic of the materials. By incorporating structural reinforcement elements, the scaffold can be made mechanically more robust for in vivo applications (Mozdzen et al, 2016;Mozdzen et al, 2017). As a result, there is a specific need to identify culture conditions to enhance tenogenic differentiation and promote extracellular matrix remodelling, in order to ensure the scaffold would remain structurally competent and fully integrate into a wound repair site.…”

Do There Exist Innovative Perspectives in Tissue Engineering-Based Ligament Reconstruction?

“…5 Through this, various biomaterials have been selected and applied for ligament tissue engineering such as synthetic such as poly lactic acid (PLA) or polyurethan, as well as natural polymers such as collagen or silk and composites of both. 6,7 Decellularized ECMs from allogenic or xenogenic donor-derived ligaments or tendons provide nearly natural tissue composition and biomechanics and therefore, present a promising approach for ligament tissue engineering. 8,9 In addition, the ECMs promote differentiation of precursor cells.…”

“…10,11 Scaffolds for ligament tissue engineering can be produced by various techniques such as braiding, embroidering, 3D printing, electrospinning, electro hydrodynamic jet printing and combinations of them. 6,10,[12][13][14][15] Aligned, interwoven and multilayered composite structures most likely reflect the natural aligned ligament ultrastructure and biomechanics. 10 Subsequently, an extensive biomaterial testing is necessary starting with the pure material to evaluate crucial parameters such as hydrophobicity/hydrophilicity, degradation, permeability, porosity, interconnectivity, surface texture and biomechanics.…”

“…Later, in combination with a model cell line and then, with the respective ligamentogenic primary cell types, cellular parameters should be assessed such as cytocompatibility, cell adherence, distribution, morphology, cytoskeletal architecture, gene and protein expression profiles including established ligament and fibroblast markers such as scleraxis, tenomodulin and tenascin C. 16 Unfortunately, many synthetic polymers such as PLA or natural polymers such as silk with promising mechanical properties allow only limited cell adherence and growth. 6,7 Therefore, functionalization of synthetic polymers is demanded. 12,13,17 Biomaterial functionalization should increase cell adherence, survival, spreading and migration, proliferation or differentiation and at least ligamentogenesis.…”

“…In the case of tendons and ligaments collagen, prepared in various formulations (such as hydrogels, coatings, foams, sponges, films) led to promising results. 6,19 Other functionalization strategies included the integration of motifs for fibronectin 16 or RGD peptides into the scaffolds to improve integrin receptor-mediated cell adherence or the addition other functional groups. 16,20 Several approaches used the slow release of stimulatory growth factors (GFs) attached to the scaffolds.…”