We report on highly stretchable piezoelectric structures of electrospun PVDF-TrFE nanofibers. We fabricated nanofibrous PVDF-TrFE yarns via twisting their electrospun ribbons. Our results show that the twisting process not only increases the failure strain but also increases overall strength and toughness. The nanofibrous yarns achieved a remarkable energy to failure of up to 98 J/g. Through overtwisting process, we fabricated polymeric coils out of twisted yarns that stretched up to ∼740% strain. This enhancement in mechanical properties is likely induced by increased interactions between nanofibers, contributed by friction and van der Waals interactions, as well as favorable surface charge (Columbic) interactions as a result of piezoelectric effect, for which we present a theoretical model. The fabricated yarns and coils show great promise for applications in high-performance lightweight structural materials and superstretchable piezoelectric devices and flexible energy harvesting applications.

Development of tendon therapeutics has been hindered by the lack of informative adult mammalian models of regeneration. Murphy Roth's Large (MRL/MpJ) mice exhibit improved healing following acute tendon injuries, but the driver of this regenerative healing response remains unknown. The tissue‐specific attributes of this healing response, despite a shared systemic environment within the mouse, support the hypothesis of a tissue‐driven mechanism for scarless healing. Our objective was to investigate the potential of MRL/MpJ tendon extracellular matrix (ECM)‐derived coatings to regulate scar‐mediated healing. We found that deviations in the composition of key structural proteins within MRL/MpJ vs C57Bl/6 tendons occur synergistically to mediate the improvements in structure and mechanics following a 1‐mm midsubstance injury. Improvement in mechanical properties of healing MRL/MpJ vs C57Bl/6 tendons that were isolated from systemic contributions via organ culture, highlighted the innate tendon environment as the driver of scarless healing. Finally, we established that decellularized coatings derived from early‐deposited MRL/MpJ tendon provisional extracellular matrix (provisional‐ECM), can modulate canonical healing B6 tendon cell behavior by inducing morphological changes and increasing proliferation in vitro. This study supports that the unique compositional cues in MRL/MpJ provisional‐ECM have the therapeutic capability to motivate canonically healing cells toward improved behavior; enhancing our ability to develop effective therapeutics.

Despite previous studies that showed enhanced cpTi corrosion activity for fluoride-containing compositions (NIB and ZP), there was no significant difference in cytotoxicity between cement alone and cemented-cpTi. In general, the MC3T3-E1 preosteoblast cells were more sensitive than HGF cells to cement composition. Ultimately, cement composition played a significant role in maintaining host cell compatibility. Results of this work help illustrate the impact of different cement formulations on host cell health and emphasize the need for understanding material properties when selecting certain formulations of dental cements, which can ultimately influence the survival of dental implant systems.

Tissue decellularization has demonstrated widespread applications across numerous organ systems for tissue engineering and regenerative medicine applications. Decellularized tissues are expected to retain structural and/or compositional features of the natural extracellular matrix (ECM), enabling investigation of biochemical factors and cell-ECM interactions that drive tissue homeostasis, healing, and disease. However, the dense collagenous tendon matrix has limited the efficacy of traditional decellularization strategies without the aid of harsh chemical detergents and/or physical agitation that disrupt tissue integrity and denature proteins involved in regulating cell behavior. In this study, we adapted and established the advantages of a detergent-free decellularization method that relies on latrunculin B actin destabilization, alternating hypertonic-hypotonic salt and water incubations, nuclease-assisted elimination of cellular material, and protease inhibitor supplementation under aseptic conditions. Our method maintained the collagen molecular structure (i.e., minimal extent of denaturation), while adequately removing cells and preserving bulk mechanical properties. Furthermore, we demonstrated that decellularized tendon ECM-derived coatings isolated from different mouse strains, injury states (i.e., naive and acutely injured/“provisional”), and anatomical sites harness distinct biochemical cues and robustly maintain tendon cell viability in vitro . Together, our work provides a simple and scalable decellularization method to facilitate mechanistic studies that will expand our fundamental understanding of tendon ECM and cell biology. Impact statement In this study, we present a decellularization method for tendon that does not rely on any detergent or physical processing techniques. We assessed the impact of detergent-free decellularization using tissue, cellular, and molecular level analyses and validated the preservation of gross fiber architecture, collagen molecular structure, and extracellular matrix (ECM)-associated biological cues that are essential for studying physiological cell-ECM interactions. Finally, we demonstrated the applicability of this method for healthy and injured tendon environments, across mouse strains, and for different types of tendons, illustrating the utility of this approach for isolating the contributions of biochemical cues within unique tendon ECM microenvironments.

Clinical and animal studies have reported the influence of sex on the incidence and progression of tendinopathy, which results in disparate structural and biomechanical outcomes. However, there remains a paucity in our understanding of the sex-specific biological mechanisms underlying effective tendon healing. To overcome this hurdle, our group has investigated the impact of sex on tendon regeneration using the super-healer Murphy Roths Large (MRL/MpJ) mouse strain. Despite a shared scarless healing capacity, we have shown that MRL/MpJ patellar tendons exhibit sexually dimorphic regulation of gene expression for pathways involved in fibrosis, cell migration, and extracellular matrix (ECM) remodeling following an acute midsubstance injury. Moreover, we previously found decreased matrix metalloproteinase-2 (MMP-2) activity in female MRL/MpJ tendons after injury. Thus, we hypothesized that MRL/MpJ scarless tendon healing is mediated by sex-specific and temporally distinct orchestration of cell-ECM interactions. Accordingly, the present study comparatively evaluated MRL/MpJ tendon cells under two-dimensional (glass) and three-dimensional (nanofiber scaffolds) culture platforms to examine cell behavior under biochemical and biophysical cues associated with tendon homeostasis and healing. Female MRL/MpJ cells showed reduced 2D migration and spreading area accompanied with enhanced mechanosensing, 2D ECM alignment, and fibronectin-dependent cell proliferation. Interestingly, female MRL/MpJ cells cultured on 3D isotropic scaffolds showed diminished ECM deposition and alignment. Regardless of culture condition and sex, MRL/MpJ cells outperformed B6 cells and elicited a universal regenerative cellular phenotype. These results illustrate the utility of these in vitro systems for elucidating regenerative tendon cell biology, which will facilitate the long-term development of more equitable therapeutics.