Actuated tissue engineered muscle grafts restore functional mobility after volumetric muscle loss.

Damage that affects large volumes of skeletal muscle tissue can severely impact health, mobility, and quality-of-life. Efforts to restore muscle function by implanting tissue engineered muscle grafts at the site of damage have demonstrated limited restoration of force production. Various forms of mechanical and biochemical stimulation have been shown to have a potentially beneficial impact on graft maturation, vascularization, and innervation. However, these approaches yield unpredictable and incomplete recovery of functional mobility. Here we show that targeted actuation of implanted grafts, via non-invasive transcutaneous light stimulation of optogenetic engineered muscle, restores motor function to levels similar to healthy mice 2 weeks post-injury. Furthermore, we conduct phosphoproteomic analysis of actuated engineered muscle in vivo and in vitro to show that repeated muscle contraction alters signaling pathways that play key roles in skeletal muscle contractility, adaptation to injury, neurite growth, neuromuscular synapse formation, angiogenesis, and cytoskeletal remodeling. Our study uncovers changes in phosphorylation of several proteins previously unreported in the context of muscle contraction, revealing promising mechanisms for leveraging actuated muscle grafts to restore mobility after volumetric muscle loss.

EMG-informed neuromuscular model assesses the effects of varied bodyweight support on muscles during overground walking.

Bodyweight supported walking is a common gait rehabilitation method that can be used as an experimental approach to better understand walking biomechanics. Neuromuscular modeling can provide an analytical means to gain insight into how muscles coordinate to produce walking and other movements. To better understand how muscle length and velocity affect muscle force during overground walking with bodyweight support, we used an electromyography (EMG)-informed neuromuscular model to investigate changes in muscle parameters (muscle force, activation and fiber length) at varying bodyweight support levels: 0%, 24%, 45% and 69% bodyweight. Coupled constant force springs provided a vertical support force while we collected biomechanical data (EMG, motion capture and ground reaction forces) from healthy, neurologically intact participants walking at 1.20 ± 0.06 m/s. The lateral and medial gastrocnemius demonstrated a significant decrease in muscle force (lateral: p = 0.002 and medial: p < 0.001) and activation (lateral: p = 0.007 and medial: p < 0.001) through push-off at higher levels of support. The soleus, in contrast, had no significant change in muscle activation through push-off (p = 0.652) regardless of bodyweight support level even though soleus muscle force decreased with increasing support (p < 0.001). During push-off, the soleus had shorter muscle fiber lengths and faster shortening velocities as bodyweight support levels increased. These results provide insight into how muscle force can be decoupled from effective bodyweight during bodyweight supported walking due to changes in muscle fiber dynamics. The findings contribute evidence that clinicians and biomechanists should not expect a reduction in muscle activation and force when using bodyweight support to assist gait during rehabilitation.

Preliminary Study of Vibrotactile Feedback during Home-Based Balance and Coordination Training in Individuals with Cerebellar Ataxia.

Intensive balance and coordination training is the mainstay of treatment for symptoms of impaired balance and mobility in individuals with hereditary cerebellar ataxia. In this study, we compared the effects of home-based balance and coordination training with and without vibrotactile SA for individuals with hereditary cerebellar ataxia. Ten participants (five males, five females; 47 ± 12 years) with inherited forms of cerebellar ataxia were recruited to participate in a 12-week crossover study during which they completed two six-week blocks of balance and coordination training with and without vibrotactile SA. Participants were instructed to perform balance and coordination exercises five times per week using smartphone balance trainers that provided written, graphic, and video guidance and measured trunk sway. The pre-, per-, and post-training performance were assessed using the Scale for the Assessment and Rating of Ataxia (SARA), SARAposture&gait sub-scores, Dynamic Gait Index, modified Clinical Test of Sensory Interaction in Balance, Timed Up and Go performed with and without a cup of water, and multiple kinematic measures of postural sway measured with a single inertial measurement unit placed on the participants' trunks. To explore the effects of training with and without vibrotactile SA, we compared the changes in performance achieved after participants completed each six-week block of training. Among the seven participants who completed both blocks of training, the change in the SARA scores and SARAposture&gait sub-scores following training with vibrotactile SA was not significantly different from the change achieved following training without SA (p>0.05). However, a trend toward improved SARA scores and SARAposture&gait sub-scores was observed following training with vibrotactile SA; compared to their pre-vibrotacile SA training scores, participants significantly improved their SARA scores (mean=−1.21, p=0.02) and SARAposture&gait sub-scores (mean=−1.00, p=0.01). In contrast, no significant changes in SARA scores and SARAposture&gait sub-scores were observed following the six weeks of training without SA compared to their pre-training scores immediately preceding the training block without vibrotactile SA (p>0.05). No significant changes in trunk kinematic sway parameters were observed as a result of training (p>0.05). Based on the findings from this preliminary study, balance and coordination training improved the participants' motor performance, as captured through the SARA. Vibrotactile SA may be a beneficial addition to training regimens for individuals with hereditary cerebellar ataxia, but additional research with larger sample sizes is needed to assess the significance and generalizability of these findings.