Appropriate macrophage response to an implanted biomaterial is crucial for successful tissue healing outcomes. In this work we investigated how intrinsic topological cues from electrospun biomaterials and extrinsic mechanical loads cooperate to guide macrophage activation and macrophage-tendon fibroblast cross-talk. We performed a series of in vitro and in vivo experiments using aligned or randomly oriented polycaprolactone nanofiber substrates in both mechanically loaded and unloaded conditions. Across all experiments a disorganized biomaterial fiber topography was alone sufficient to promote a pro-inflammatory signature in macrophages, tendon fibroblasts, and tendon tissue. Extrinsic mechanical loading was found to strongly regulate the character of this signature by reducing pro-inflammatory markers both in vitro and in vivo. We observed that macrophages generally displayed a stronger response to biophysical cues than tendon fibroblasts, with dominant effects of cross-talk between these cell types observed in mechanical co-culture models. Collectively our data suggest that macrophages play a potentially important role as mechanosensory cells in tendon repair, and provide insight into how biological response might be therapeutically modulated by rational biomaterial designs that address the biomechanical niche of recruited cells.

Introduction: Quantifying muscle strength is critical in clinical and research settings. A rapid and objective method is ideal. The primary objective of this study was to examine the reliability of a novel device, the rapid objective quantification― tibialis anterior (ROQ‐TA), which quantifies the dorsiflexion force of the tibialis anterior, and to assess its validity against isokinetic dynamometry (IKD). Methods: Ankle dorsiflexion of 20 healthy subjects was assessed by 3 modalities, ROQ‐TA, manual muscle testing, and isokinetic dynamometry, over 2 testing sessions. Results: The intraclass correlation coefficient [ICC(2,1)] for reliability was 0.872 (0.677–0.949) for the ROQ‐TA and 0.892 (0.728–0.957) for IKD. For validity, the ICC(2,1) values for the ROQ‐TA and IKD were in good agreement, with 0.672 (0.17–0.87) in the first testing session and 0.769 (0.42–0.91) in the second session. Discussion: The ROQ‐TA is a valid and reliable device to test ankle dorsiflexion force in a healthy population. Muscle Nerve, 2018

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