Electrospun meshes possessing region‐wise differences in fiber orientation, diameter, chemistry and mechanical properties for engineering bone‐ligament‐bone tissues

Abstract

Although bone-patellar tendon-bone (B-PT-B) autografts are the gold standard for repair of anterior cruciate ligament ruptures, they suffer from drawbacks such as donor site morbidity and limited supply. Engineered tissues modeled after B-PT-B autografts are promising alternatives because they have the potential to regenerate connective tissue and facilitate osseointegration. Towards the long-term goal of regenerating ligaments and their bony insertions, the objective of this study was to construct 2D meshes and 3D cylindrical composite scaffolds - possessing simultaneous region-wise differences in fiber orientation, diameter, chemistry and mechanical properties - by electrospinning two different polymers from off-set spinnerets. Using a dual drum collector, 2D meshes consisting of an aligned polycaprolactone (PCL) fiber region, randomly oriented poly(lactide-co-glycolide) (PLGA) fiber region and a transition region (comprised of both PCL and PLGA fibers) were prepared, and region-wise differences were confirmed by microscopy and tensile testing. Bone marrow stromal cells (BMSCs) cultured on these meshes exhibited random orientations and low aspect ratios on the random PLGA regions, and high aspect ratios and alignment on the aligned PCL regions. Next, meshes containing an aligned PCL region flanked by two transition regions and two randomly oriented PLGA regions were prepared and processed into 3D cylindrical composite scaffolds using an interpenetrating photo-crosslinkable polyethylene glycol diacrylate hydrogel to recapitulate the shape of B-PT-B autografts. Tensile testing indicated that cylindrical composites were mechanically robust, and eventually failed due to stress concentration in the aligned PCL region. In summary, this study demonstrates a process to fabricate electrospun meshes possessing region-wise differences in properties that can elicit region-dependent cell responses, and be readily processed into scaffolds with the shape of B-PT-B autografts.

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors

“…In addition, collagen type I produced by the fibroblasts exhibited a high degree of organization (alignment and parallelism) in the aligned fiber scaffold compared to a random distribution in the random fiber scaffold. Similarly, Satyavrata Samavedi et al[80] obtained comparable results when analyzing cell morphology, orientation and cytoskeleton bone marrow-derived mesenchymal stem cells (BMSCs) cultured on aligned PCL vs random PLGA electrospun fibers. Taken together, these results show that nanofiber organization and alignment can be modulated during fabrication to guide cell response.…”

Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces

“…[116] PLGA randomly oriented nanofibers PCL aligned nanofibers Electrospun 2D meshes and 3D cylindrical composites with controlled fiber orientation, diameter, chemistry, and mechanical properties. [120] The 3D cylindrical composite lacked mechanical strength in the aligned PCL region. [120] Figure 1: Orthopedic interface tissues include bone-cartilage, tendon-bone, and ligament-bone interfaces.…”

“…[120] The 3D cylindrical composite lacked mechanical strength in the aligned PCL region. [120] Figure 1: Orthopedic interface tissues include bone-cartilage, tendon-bone, and ligament-bone interfaces. In all these interfaces, a gradual transition in structure, chemical composition, and cell types between the two tissues are observed.…”

“…[117] Another nontraditional approach to bone-ligament regeneration involved fabrication of two-and three-dimensional electrospun scaffolds. [120] PCL and PLGA were respectively chosen for the aligned and random portions of the scaffold and the transition region contained both materials (Figure 8a,b).…”

Engineering Complex Orthopaedic Tissues Via Strategic Biomimicry

“…Inspired by these multi-tissue structures, a variety of complex scaffold designs seeking to recapitulate the native spatial and compositional inhomogeneity have been developed. 4,28,77 This review will discuss current regenerative engineering efforts in ligament-bone, 3,11,19,20,54,62,68,71,72,86,87,96–98,110,111,113–115 tendon-bone, 24,78,79,137 muscle-tendon, 57,58,60,117,118 and cartilage-bone integration, 1,5,13,15–18,25–27,30,32,33,36,37,39,41,47,49,52,53,55,56,69,74,91,95,100–104,106,119,128,133–136 focusing on biomaterial- and cell-based strategies for engineering biomimetic, functional spatial variations in composition and mechanical properties. In light of the complexity of multi-tissue regeneration, the application of strategic biomimicry across tissue-tissue junctions, or prioritizing what needs to be recapitulated from native tissues and identifying the most crucial parameters for complex scaffold design, is essential for avoiding over-engineering the scaffold system.…”