Spinal cord injury (SCI) is a devastating health problem for tens of thousands of military personnel, Veterans and civilians annually. Many persons with SCI must use a wheelchair for their entire life. A new scientific breakthrough called "lumbosacral epidural stimulation" or "ES" can help people with SCI to stand, step and even walk again. At present, for ES to work, people must train with a specialized treadmill that requires several other qualified personnel to train them, which makes it hard for many people with SCI to benefit from this technology. On the other hand, there are wearable "robot suits" that can be used with ES, which would make it easier to use. Our research team has already used this "ES Robot Suit" for 3 months in one person with tetraplegia and showed remarkable improvements in motor control. Furthermore, the investigators are aiming to enhance overground motor recovery by adding 6 months of resistance training (RT). The addition of RT will likely to enhance muscle quality as indicated by increasing lean mass, peak torque and increase sensory flux to the central nervous system. Other additional benefits may include improvement in cardiovascular profile and bladder functions. The specific objectives of the current proposal are to compare the impact of EAW+ES following improving lower extremity muscle quality compared to those who will only undergo EAW+ ES without conducting RT on motor recovery, cardio-metabolic health and bladder control in persons with complete SCI. At the conclusion of the current proposal, the work will be readily available for translation into clinical setting to serve Veterans and Civilian survivors with SCI.

Spinal cord epidural stimulation (ES) is a neuromodulation modality that can facilitate standing, stepping and walking with and without assistive devices in individuals with SCI, however; ES must be accompanied with locomotor training that at present requires a labor-intensive commitment from multiple well-trained personnel using specialized treadmill equipment. Exoskeletal assisted walking (EAW) on the other hand can be safely and efficiently used for ambulation after SCI in combination with ES without the use of other specialized equipment and multiple personnel. The investigators demonstrated that 12-weeks of EAW+ ES resulted in volitional stepping, with improved temporal and rhythmic electromyography (EMG) patterns and speed and with a reduction in EAW assistance to 35%. Unfortunately, EAW+ES does not appear to effectively restore lean mass below the level of injury, which impacts proprioceptive feedback to the spinal locomotor centers. Thus, in addition the investigators have demonstrated that 16-weeks of electrically-evoked resistance training (RT) resulted in robust muscle hypertrophy of the paralyzed knee and hip extensor muscle groups. Therefore, this proposal leverages these research programs by addressing two major gaps; 1) the use of combination EAW+ES as an activity-dependent plasticity tool for restoration of over ground locomotion and 2) enhancement of muscle quality using RT to provide afferent leverage for neuromodulation techniques.

Specific Aims:

1. To determine the impact of 12 months of EAW+ES+RT on 10-meter over ground walking-speed, number of EAW unassisted steps and EMG patterning compared to 12-months of EAW+ delayed-ES +no-RT (control group).
2. To determine the impact of 12-months of EAW+ES+RT on blood pressure, total and regional body composition, oxygen uptake as well as anabolic and inflammatory biomarkers compared to the control group.
3. To determine the impact of 12-months of EAW+ES+RT on parameters of bladder filling and emptying as measured by urodynamic studies compared to the control group.

Inclusion Criteria:

1. All participants will be between 18-60 years old, male or female, with traumatic motor complete SCI and level of injury of T10 and above, as determined by EMG testing and International Standards for Neurological Classification of SCI (ISNCSCI) exam.
2. Participants' knee extensors must respond to standard surface NMES procedures (frequency: 30 Hz; pulse duration:450 μs and amplitude of the current:200 mA) to ensure intact neural circuitry below the level of SCI.
3. All participants will undergo ISNCSCI examination for neurological level and function and only those with American Spinal Injury Classification (AIS A and B; i.e. motor deficit below the level of injury) will be included.

Exclusion Criteria:

1. Diagnosis of neurological injury other than SCI, including cauda equina or distal conus injuries resulting in limb or sacral areflexia;
2. Unhealed fracture in either lower or upper extremities;
3. Severe scoliosis, hip knee range of motion (ROM) or flexion knee contractures preventing positioning in an exoskeleton or plantarflexion contracture greater than 20 degrees.
4. Untreated or uncontrolled hypertension defined as high resting blood pressure greater than 140/90 mmHg and severe orthostatic hypotension (drop greater than 20 mmHg compared to resting supine blood pressure) or incapable to maintain a sitting or EAW standing posture;
5. Other medical conditions including cardiovascular disease, uncontrolled type II DM, uncontrolled hypertension, and those on insulin, pressures sores stage 3 or greater, or symptomatic urinary tract infection;
6. Unable to fit in the device for any reason;
7. Taking anti-coagulants or anti-platelet agents, including aspirin if unable to be off this medication for medical reasons;
8. Implanted pacemakers and/or implanted defibrillator devices;
9. DXA T-Score less than -2.5. Scans done will include total body, dual hips and knees. Total hip BMD T-scores < -3.5 and knee BMD scores of less than 0.6 g/cm2 68-71;
10. Functional upper and lower extremity ROM, strength, spasticity and skin integrity will also have assessed prior to enrollment in the program. The Modified Ashworth Scale will be used to ensure safety of the participants prior to engagement in the rehabilitation program. Participants with severe spasticity or limited ROM will be excluded from the trial. This is based on the Ekso® manufacturer's recommendations72;
11. Untreatable severe spasticity judged to be contraindicated by the site Physician;
12. Pressure ulcer of the trunk, pelvic area, or lower extremities of grade 3 or more;
13. Psychopathology documentation in the medical record or history that may conflict with study objectives;
14. Any condition that, in the judgment of the principal investigator or medical provider, precludes safe participation in the study and/or increases the risk of infection.