Opposite edges of the film were rolled to meet each other, forming a hollow tube through heat sealing, which underwent controlled thermal drawing longitudinally to create pores and surface structures elongated along the longitudinal axis ( Fig. To form the shell portion, a bioresorbable poly(ε-caprolactone) (PCL) film first underwent laser perforation to create round through-holes. For instance, an orthopedic surgeon will favor the use of a rigid steel bone plate to stabilize a complex fracture site over a biomaterial that promises complete bioresorbability and excellent host-tissue regeneration but does not offer the mechanical robustness and strength of a steel plate. Currently, most medical implants prioritize bulk material properties over microstructural intricacies because, clinically, implant safety and feasibility of application are of paramount concern. This need is particularly relevant for solutions involving the repair of force-transmitting tissues such as tendons and ligaments, where the biomechanical demands of these solutions impose the fundamental criterion of high mechanical robustness, which most experimental scaffolds fail to meet. At present, there exists an unmet need of enabling the translation of microarchitectural principles into actual clinical applications. Other attempts to biofunctionalize existing materials with topological features face problems of insufficient porosity in the base material, thus preventing cell migration and blood supply. Engineering of highly precise and well-defined microarchitecture onto a biomaterial is often complex and tedious, and the scaffolds with these features are susceptible to surface and material disintegration during physical manipulation. Despite these advances, clinical translation of these well-established principles persists as a significant challenge. To date, many studies have featured the use of various topographical geometries and arrangements to achieve specific cell responses ( 15). Altering parameters such as feature arrangement and fiber alignment has shown to have profound effects on cell shape ( 12), growth characteristics ( 13), migration ( 14), and even cell fate ( 15). Among the key principles are designing substrates with various topographies in the range of tens to hundreds of nanometers ( 10, 11) to engage focal adhesions or in the range of a few tenths of a micrometer ( 6, 9) to direct individual cells. Hence, recapitulating the structure-function relationship of tissues has been a goal for tissue engineering, and multiple studies have emphasized the importance of designing biomaterials with specific microarchitectural structures to direct tissue organization and cell alignment ( 1, 6– 9). These complex yet well-defined macro/microarchitectural attributes give rise to the unique functions of these tissues ( 3– 5). For most specialized tissues, it is the structural anisotropy and hierarchical organization of the ECM that form the stage for their functions, ranging from the soft (neuron), to moderately stiff (skin, heart, blood vessel, and muscles), to stiff (ligament, tendon, and bone) tissues ( 1, 2). Living cells reside within an intricate milieu of soluble biomolecules, cell-cell interactions, and extracellular matrices (ECM). When implanted in an in vivo micropig model, a neotissue that formed over the scaffold resembled native tendon tissue in composition and structure. Moreover, highly aligned intracellular cytoskeletal network and high nuclear alignment efficiencies were observed, suggesting that microstructural anisotropy might play the epigenetic role of mechanotransduction. When tenocytes were cultured in vitro on the scaffold, phenotypic markers of tenogenesis such as type-I collagen, decorin, and tenascin were significantly expressed over nonanisotropic controls. The scaffold was composed of two distinct portions, which enabled high porosity while retaining tendon-like mechanical properties. We report a polymeric three-dimensional scaffold with tendon-like mechanical properties and controlled anisotropic microstructures. Furthermore, compromises to biomechanical robustness during fabrication often limit the scaffold’s relevance in translational medicine. Attempts to exploit the interplay between cells and their immediate environment have rarely featured macroscale, three-dimensional constructs required for clinical applications. Structural and hierarchical anisotropy underlies the structure-function relationship of most living tissues.

Protein scaffold roc curves