9 Background: Foot and ankle unloading is essential in various clinical contexts, including 10 ulcers, tendon ruptures, and fractures. Choosing the right assistive device is crucial for func- 11 tionality and recovery. Yet, research on the impact of devices beyond crutches, particularly 12 ankle-foot orthoses (AFOs) designed to unload the ankle and foot, is limited. This study 13 investigates the effects of three types of devices - forearm crutches, knee crutch, and AFO 14 - on biomechanical, metabolic, and subjective parameters during walking with unilateral 15 ankle-foot unloading. 16 Methods: Twenty healthy participants walked at a self-selected speed in four conditions: 17 unassisted able-bodied gait, and using three unloading devices, namely forearm crutches, 18 iWalk knee crutch, and ZeroG AFO. Comprehensive measurements, including motion capture, 19 force plates, and metabolic system, were used to assess various spatiotemporal, kinematic, 20 kinetic, and metabolic parameters. Additionally, participants provided subjective feedback 21 through questionnaires. The conditions were compared using a within-subject crossover study 22 design with repeated measures ANOVA. 23 Results: Significant differences were found between the three devices and able-bodied gait. 24 Among the devices, ZeroG exhibited significantly faster walking speed and lower metabolic 25 cost. For the weight-bearing leg, ZeroG exhibited the shortest stance phase, lowest braking 26 forces, and hip and knee angles most similar to normal gait. However, ankle plantarflexion 27 after push-off using ZeroG was most different from normal gait. IWalk and crutches caused 28 significantly larger center-of-mass mediolateral and vertical fluctuations, respectively. Par- 29 ticipants rated the ZeroG as the most stable, but more participants complained it caused 30 excessive pressure and pain. Crutches were rated with the highest perceived exertion and 31 lowest comfort, whereas no significant differences between ZeroG and iWalk were found for 32 these parameters. 33 Conclusions: Significant differences among the devices were identified across all measure- 34 ments, aligning with previous studies for crutches and iWalk. ZeroG demonstrated favorable 35 performance in most aspects, highlighting the potential of AFOs in enhancing gait rehabil- 36 itation when unloading is necessary. However, poor comfort and atypical sound-side ankle 37 kinematics were evident with ZeroG. These findings can assist clinicians in making educated 38 decisions about prescribing ankle-foot unloading devices and guide the design of improved 39 devices that overcome the limitations of existing solutions. 40 1 Keywords: Ankle-foot orthosis (AFO), crutches, gait analysis, gait rehabilitation, hands- 41 free crutch, joint kinematics, knee crutch, metabolic cost, non-weight-bearing. 42 1 Background 43 Numerous medical conditions affect the foot and ankle, including diabetic foot ulcers, Charcot 44 neuroarthropathy, Achilles tendon ruptures, foot and ankle fractures and sprains, and surgical 45 procedures such as ankle replacement or fusion. These conditions often require the patients to un- 46 load the affected leg for prolonged durations. For example, previous studies have reported periods 47 of approximately 4-8 weeks for ankle fractures [1], up to 24 weeks for Charcot osteoarthropathy 48 [2], and up to 38 weeks for diabetic ulcers [3]. Consequently, ambulatory assistive devices are com- 49 monly prescribed to facilitate ambulation while avoiding undesired weight-bearing of the affected 50 leg [4]. 51 Currently, crutches constitute the standard care for enabling patients to walk without loading 52 their ankle or foot [5] (Fig. 1a). Compared to wheelchairs, crutches allow greater mobility and 53 functionality, which are beneficial to patient health and rehabilitation outcomes [6]. However, 54 studies have shown that crutch gait tends to be slower and less energetically efficient than normal 55 gait [5, 7–10], and limits the use of the upper extremities [11]. Compared to normal gait, crutches 56 alter the walking pattern, joint kinematics, and ground reaction force (GRF) patterns [8, 12–14]. 57 The unloading and immobilization of the affected leg may cause muscle atrophy and bone density 58 decrease in the unloaded leg [15–18]. For example, significant reductions in thigh and calf muscle 59 tissue cross-sectional area were found after four weeks of non-weight-bearing in patients with foot 60 fractures [15], and bone density significantly decreased after six weeks of non-weight-bearing and 61 continued to decrease even after 6 and 13 weeks of full weight-bearing [18]. Furthermore, crutch 62 usage may lead to increased loading on the weight-bearing leg and upper extremities, which could 63 be detrimental to some patients, particularly in prolonged use {[12, 19–22]. Specifically, one- 64 leg swing-through crutch gait has been cautioned against for patients with diseased bones and 65 joints in the lower limb, due to the increased GRFs on the weight-bearing leg [12, 19]. Moreover, 66 the reaction forces transmitted to the arms could be harmful to patients with unsound upper 67 extremities and may be linked to secondary conditions such as hematoma formation, Ulnar nerve 68 compression neuropathy, and Ulnar stress fractures [12, 20–22]. 69 Recently, alternative devices have been proposed for unloading the foot and ankle while walking. 70 One such device is the iWalk knee crutch (iWALKFree, Inc., Long Beach, CA, USA), which enables 71 hands-free gait with a non-weight-bearing status of the lower leg. Its structure consists of a single 72 L-shaped crutch, onto which the user’s shank and thigh are secured via straps. During walking, 73 the knee is maintained at a flexed 90-degree angle, and the foot and ankle are unloaded (Fig. 1b). 74 Previous research has demonstrated that walking with iWalk is associated with reduced upper 75 limb discomfort and superior patient-perceived exertion and preference compared to traditional 76 axillary crutches [23]. Furthermore, a previous study has found that walking with iWalk causes 77 only slight changes in the biomechanical gait patterns examined in the unaffected limb, compared 78 with normal gait [24]. 79 Another type of device that may provide ankle-foot unloading, is an ankle-foot orthosis (AFO). 80 Particularly, an AFO can be designed such that the GRFs are transferred to the shank via a 81 brace tightened around it while maintaining complete unloading of the affected foot. While most 82 AFOs are custom-designed and fitted to patients in specialized clinics, the ZeroG AFO (Certified 83 Orthopedics, Inc., Fort Collins, CO, USA) claims to be the only prefabricated brace that offers 84 complete unloading of the foot and ankle [25] (Fig. 1c). Extensive research exists on AFOs that 85 2 provide ankle support for conditions such as muscle weakness, motor control deficits, spasticity, 86 and instability [26–29]. Moreover, the effects of braces and casts that provide partial offloading on 87 plantar pressure have been studied[30, 31]. However, to our knowledge, biomechanical analyses of 88 unloading AFOs, such as the ZeroG, have not been published. Nevertheless, we anticipate that 89 unloading AFOs may be advantageous over crutches for several reasons. First, similarly to the knee 90 crutch, they allow for increased mobility of the upper extremities. Second, they allow mobility and 91 loading of the proximal affected leg (above the injured distal part), which may promote a more 92 symmetric and natural walking pattern and lower metabolic cost. Finally, as discussed above, they 93 have the potential to mitigate adverse effects on the proximal bones, joints, and muscles. 94 This study aims to investigate the biomechanical, metabolic, and subjective outcomes of walk- 95 ing with three different ankle-foot unloading devices compared to unassisted normal gait (NG). 96 Using a within-subject crossover study design with repeated measures, we compared each partic- 97 ipant’s NG with their gait using three devices: forearm crutches (CR), iWalk (IW), and ZeroG 98 (ZG), as shown in 1). The experiments consisted of 20 healthy participants walking at self-selected 99 speed at each of the four conditions. The three-dimensional kinematics of the joints and the center 100 of mass (CoM), the GRFs, and metabolic cost were measured, and the participants provided sub- 101 jective ratings for stability, perceived exertion, comfort, pressure, and pain through questionnaires. 102 The comparison of joint kinematics and GRF focused on the weight-bearing limb since it allows for 103 direct comparison between the conditions, and because increased GRFs and atypical kinematics of 104 the weight-bearing leg can cause overstrain and secondary injuries, as previous studies have shown 105 in the case of crutches. 106 We hypothesize that all devices will significantly alter gait parameters compared to normal gait. 107 However, we expect the ZeroG to result in smaller gait alterations because it permits mobility and 108 loading of the unloaded leg’s knee and hip joints. Additionally, we anticipate that crutches would 109 lead to increased GRF peaks and metabolic cost, similar to previous studies, and that iWalk would 110 cause increased CoM mediolateral fluctuations because the locked knee requires hip circumduction 111 to swing the device forward. 112 {The findings from this study could help elucidate the quantitative effects of each device on 113 different biomechanical parameters. This knowledge could be valuable for clinicians in prescribing 114 the most suitable device for each patient’s individual condition, in order to improve their func- 115 tionality during recovery and minimize the risk of adverse effects associated with the device. This 116 knowledge could be particularly important in cases that require prolonged periods of ankle-foot 117 unloading, as the accumulated impact can become more pronounced. Furthermore, the insights 118 gained from this study could inform the design of improved devices that overcome the limitations 119 of existing devices. 120 2 Methods 121 2.1 Devices 122 Three devices for unilateral foot-ankle unloading were selected for this study: 123 1. Forearm crutches (CR), also known as Canadian crutches. We used the model Access Com- 124 fort (FDI FRANCE M ´EDICAL, Fitilieu, France), weight: 0.48 kg (Fig. 1a). 125 2. iWalk (IW), version 2.0 (iWALKFree, Inc., Long Beach, CA, USA), weight: 2.09 kg (Fig. 1b). 126 3. ZeroG (ZG) AFO (Certified Orthopedics, Inc., Fort Collins, CO, USA), size medium calf 127 lacer and AFO base, weight: 1.49 kg (Fig. 1c).A gel liner (ComfortZone ™Ultra Cushion, 128 Silipos Holding LLC., NY, USA) was worn to add cushioning between the calf lacer and the 129 3 Figure 1: The ankle-foot unloading devices examined in this study: (a) Forearm crutches (CR), (b) iWalk 2.0 (IW), (c) Zero-G Ankle Foot Orthosis (ZG). All the devices were used such that only one foot is weight-bearing and the other one is completely unloaded. shank. A shoe leveler (EVENup, Oped Medical, Inc., Buford, GA, USA) was added under 130 the shoe of the weight-bearing foot to equate the length of both legs, as recommended by 131 the manufacturer. During our preliminary testings, we encountered difficulties preventing 132 contact between the forefoot and the AFO base, especially during late stance. To address this 133 issue, we added a wide strap to the calf lacer, which helped provide support to the forefoot 134 and prevent plantarflexion. This ensured that unloading was maintained throughout the gait 135 cycle. 136 2.2 Study population 137 Twenty healthy participants were recruited (9 males and 11 females, age: 27.2 ±5.5 years, height: 138 167.1 ±6.9 cm, mass: 65.3 ±8.9 kg). All participants were free from current injury or any 139 condition that might affect typical walking patterns. Moreover, all participants were within the 140 sizing range suitable for the medium-size ZeroG, per the manufacturer’s fitting instructions. The 141 study was approved by the Institutional Review Board at Technion (#108-2020). Before their 142 inclusion and following a detailed explanation of the study requirements, participants provided 143 written informed consent. 144 2.3 Experimental Protocol 145 Participants visited the Mechanical Engineering Faculty at the Technion on two consecutive days. 146 On the first visit, a certified physical therapist fitted the devices on the non-dominant leg. Leg 147 dominance was determined by asking participants which leg they would use to kick a ball. Par- 148 ticipants were instructed to completely unload their non-dominant leg when walking (i.e., lifting 149 their non-dominant leg completely off the floor using CR, and ensuring the plantar foot surface 150 is unloaded when using ZG). After familiarization with each device, the participants performed 151 a six-minute walking test (6MWT) at a self-selected speed along an indoor 50 m corridor. First, 152 they walked without any device (NG condition) and then with each device in random order. The 153 Oxygen consumption (VO 2) was measured using a wearable metabolic system (K5, COSMED, 154 Rome, Italy), and the distance walked at each 6MWT was recorded for calculating the mean 155 4 walking speed. After each condition, the participants were given a ten-minute rest period, during 156 which they filled out a questionnaire, rating their perceived exertion, stability, and comfort, on a 157 0-10 scale. Additionally, they were asked to indicate any pain or pressure regions caused by the 158 devices (using a body chart) and rate them on a 0-10 scale. On the second visit, the participants 159 arrived at the Technion BRML laboratory, where a 16-camera three-dimensional motion capture 160 system (Vicon Motion Systems Ltd, Oxford, UK) was used to collect kinematic data at 120Hz. 161 Participants were fitted with 39 reflective markers according to the Plug-In-Gait Full body model. 162 Walking trials consisted of walking at a self-selected speed along a 10m straight walkway equipped 163 with two floor-embedded force plates (OR6-7-1000, AMTI Inc., Watertown, MA, USA), recording 164 the GRF at 960Hz. For each condition, 10-20 gait cycles (GCs) were recorded, and the conditions 165 were conducted in the same random order as in the first visit. 166 2.4 Data processing 167 The metabolic cost for each condition was calculated by normalizing the mean VO 2by the par- 168 ticipant’s body mass. The data were subsequently normalized by the walking speed (calculated 169 from the walking distance during the 6MWT), which reflects its efficiency, i.e., the aerobic demand 170 per unit of distance walked [32]. The marker trajectories and the GRF data were processed using 171 Nexus 2.9.3 software (Vicon Motion Systems Ltd, Oxford, UK) to extract the hip, knee, and ankle 172 sagittal plane joint angles, body center of mass (CoM) trajectories, and the initial contact (IC) 173 and toe-off (TO) gait events. GCs in which the participant stepped on the edges of the force 174 plate were excluded from the analysis. The raw signals of the joint angles and GRF were filtered 175 using a low-pass Butterworth filter, using a 4th-order filter with a cut-off frequency of 6Hz and 176 a 2nd-order filter with a cut-off frequency of 10Hz, respectively. For each trial, the GC of the 177 weight-bearing leg was defined between two consecutive ICs, and the stance phase duration was 178 defined from IC to TO. Consequently, all GCs were temporally aligned and interpolated between 179 0-100%. Moreover, the GRFs were normalized by each participant’s body weight. Furthermore, 180 the minimum and maximum local peaks of the joint angles and the anterior-posterior and vertical 181 components of the GRF were identified. Note that the analysis of joint angles and GRF focused 182 on the weight-bearing leg to allow direct comparison between the devices since the unloaded leg is 183 supported differently in each condition (free to move and completely unloaded using CR, loaded 184 from the knee upwards with a fixed knee flexion using IW, and loaded from the shank upwards 185 with the knee free to articulate using ZG). 186 2.5 Statistical analysis 187 The statistical analysis was carried out using SAS 9.4 (SAS Institute Inc., Cary, NC). Normality 188 tests were conducted using the Kolmogorov-Smirnoff test for the following parameters: GRF peaks, 189 CoM range of fluctuation, joint angles peaks, walking speed, metabolic cost, stance phase duration, 190 and subjective parameters. To analyze the intra-subject differences, a one-way Analysis of Variance 191 (ANOVA) model with repeated measures was applied. Significant differences between pairs were 192 determined using the studentized maximum modulus multiple comparison adjustment method, 193 also known as Hochberg’s GT2 [33], which is utilized to evaluate significant differences between 194 group means in the context of multiple pairwise comparisons. To address the violation of the 195 normality assumption of ANOVA, the variables that exhibited a non-normal distribution were 196 corrected by applying a monotonically ranked transformation. If the distribution remained non- 197 normal after the transformation, a Friedman test was performed, a post-hoc analysis was carried 198 5 out using Wilcoxon signed-rank tests, and a Bonferroni correction was applied. A significance level 199 ofp <0.05 was considered statistically significant. 200 3 Results 201 All the parameters followed a normal distribution except for hip angle peaks, CoM in both di- 202 rections, the first peak of vertical GRF, and the perceived exertion. Only the latter remained 203 non-normal after the transformation. All the results of the statistical analysis are provided in the 204 supplementary file S1. 205 3.1 Spatiotemporal, metabolic, and subjective parameters 206 The results of the average walking speed and the metabolic cost measured during the 6MWT are 207 presented in Fig. 2a and Fig. 2b, respectively. All the devices caused a significant ( p <0.0001) 208 reduction in walking speed compared to NG (1.19 m/s). Among the devices, walking with the ZG 209 (0.78 m/s) was significantly faster than walking with CR and IW (0.47 and 0.52 m/s, respectively). 210 All the devices exhibited significantly greater metabolic cost than NG. Among the devices, ZG 211 resulted in significantly lower metabolic cost than IW ( p= 0.0006) and CR ( p <0.0001). The 212 stance phase durations are shown in Fig. 2c. All devices resulted in significantly longer stance 213 phase duration relative to NG (62%GC, p <0.0001), with ZG (68%GC) significantly shorter than 214 CR (76%GC, p= 0.0005) and IW (72%GC, p= 0.0011). 215 The subjective participant ratings are presented in Fig. 2(d-f). The perceived exertion using 216 CR was significantly higher than both IW ( p= 0.0004) and ZG ( p <0.0001), which showed similar 217 ratings ( p <0.0001). CR was also rated significantly less comfortable than IW( p= 0.002), with 218 nonsignificant differences between the other pairs. ZG was rated significantly more stable than IW 219 (p= 0.017) and CR ( p= 0.042), which showed nonsignificant differences. 220 3.2 Joint kinematics 221 The results of the weight-bearing leg’s hip, knee, and ankle sagittal plane angles are shown in 222 Fig. 3, Fig. 4, and Fig. 5, respectively. In each figure, panel (a) depicts the angles over a GC, 223 panels (b) and (d) present selected peak values, and panels (c) and (e) the corresponding %GC in 224 which they occurred. The full statistical results are provided in the supplementary file S1. 225 Compared to NG, the first peak of the hip angle, corresponding to the maximum hip flexion 226 at the beginning of the stance phase, was significantly higher for IW and nonsignificantly different 227 for the other conditions. While this peak occurred right at IC for NG, all the devices significantly 228 delayed its timing. The second peak, which typically corresponds to the maximum hip extension 229 during late stance, was most significantly altered using CR, resulting in the absence of hip exten- 230 sion. Moreover, IW and ZG also caused a significant reduction and delay in hip extension, with 231 the most extended delay obtained for CR, followed by IW and ZG. 232 The first peak of the knee angle, which corresponds to the maximum flexion during stance, 233 exhibited a significant increase using CR compared to all other conditions. Conversely, using IW 234 and ZG resulted in no significant differences from NG. The peak occurred significantly earlier 235 using CR and IW, whereas ZG exhibited no significant difference relative to NG. The second peak, 236 corresponding to the maximum knee flexion during swing, significantly decreased with all devices. 237 However, ZG showed a significantly smaller reduction than CR and IW. All the devices resulted 238 in significantly delayed timing relative to NG, with the longest delay obtained for CR, followed by 239 IW and ZG. 240 6 NG CR IW ZG0.511.5[m/s](a) Walking speed NG CR IW ZG0.050.10.150.2 [(ml /min/kg)/(m)](b) Metabolic cost NG CR IW ZG606570758085[%GC ](c) Stance Phase CR IW ZG0246810(d) Comfort CR IW ZG246810(e) Perceived Exertion CR IW ZG246810(f) Stability Figure 2: Summary statistics of the scalar parameters examined. The black horizontal lines indicate nonsignificant differences between paired conditions. (a) Walking speed during the 6MWT, (b) metabolic cost, (c) stance phase duration during the second-visit walking trials, (d) rated comfort, (e) rated perceived exertion, and (f) rated stability. The ankle angle first peak, corresponding to the maximum ankle dorsiflexion during late stance, 241 showed no significant differences between the conditions. However, all the devices exhibited a delay 242 in the peak, compared to NG. The second peak, corresponding to the maximum plantarflexion after 243 push-off, significantly decreased using ZG and was significantly delayed by all the devices compared 244 to NG. 245 3.3 Center of mass 246 The mediolateral and vertical trajectories of the CoM are illustrated in Fig. 6. In the mediolateral 247 direction, IW and CR exhibited significantly larger and lower CoM fluctuation ranges than all 248 other conditions, respectively. The vertical CoM fluctuation range was similar for NG, IW, and 249 ZG, whereas CR exhibited significantly larger fluctuations than all the other conditions. 250 3.4 Ground reaction forces 251 Fig. 7 summarizes the results of the vertical and anterior-posterior GRFs of the weight-bearing 252 leg over the stance phase. The first peak of the vertical GRF, occurring during weight acceptance, 253 significantly increased using CR, compared to all other conditions. Moreover, it occurred signif- 254 icantly earlier using all devices than in NG, with the CR causing the most significant difference, 255 followed by IW and ZG, the latter being closest to NG. The second peak of the vertical GRF, 256 occurring during push-off, was significantly reduced using all the devices, with no significant dif- 257 ferences among them. Moreover, for all the devices, the second peak occurred significantly earlier 258 than in NG despite a larger variance caused by the flatter peaks. The magnitude of the first peak 259 7 NG CR IW ZG204060[deg](b) 1st Peak angle NG CR IW ZG051015[%GC ](c) 1st Peak %GC NG CR IW ZG-20020[deg](d) 2nd Peak angle NG CR IW ZG50607080[%GC ](e) 2nd Peak %GC Figure 3: Sagittal plane hip angles of the weight-bearing leg. (a) Hip flexion-extension angles over a GC. The solid lines represent the medians, the shaded areas represent the range of all GCs, and the dashed vertical lines represent the mean of the TO events. (b)-(e) Summary statistics of the 1stpeak of hip flexion angle (b) and timing (c), and the 2ndpeak of hip extension angles (d) and its timing (e). The black horizontal lines indicate nonsignificant differences. NG CR IW ZG0204060[deg](b) 1st Peak angle NG CR IW ZG101520[%GC ](c) 1st Peak %GC NG CR IW ZG406080[deg](d) 2nd Peak angle NG CR IW ZG758085[%GC ](e) 2nd Peak %GC Figure 4: Sagittal plane knee angles of the weight-bearing leg. (a) Knee flexion-extension angles over a GC. The solid lines represent the medians, the shaded areas represent the range of all GCs, and the dashed vertical lines represent the mean of the TO events. (b)-(e) Summary statistics of the 1stknee flexion peak (b) and its timing (c), and the 2ndknee flexion peak (d) and its timing (e). The black horizontal lines indicate nonsignificant differences. of the anterior-posterior GRF, corresponding to the braking force during weight acceptance, most 260 significantly increased using CR and showed no significant difference between ZG and NG. This 261 peak occurred significantly earlier using all devices, with the most significant difference for CR, 262 followed by IW and ZG. The second peak, corresponding to the propulsion force during late stance, 263 was less affected by the devices, although significant reductions in force and timing were exhibited 264 for ZG. 265 8 NG CR IW ZG102030[deg](b) 1st Peak angle NG CR IW ZG50607080[%GC ](c) 1st Peak %GC NG CR IW ZG-30-20-10010[deg](d) 2nd Peak angle NG CR IW ZG708090[%GC ](e) 2nd Peak %GC Figure 5: Sagittal plane ankle angle of the weight-bearing leg. (a) Ankle dorsiflexion-plantarflexion angles over a GC. The solid lines represent the medians, the shaded areas represent the range of all GCs, and the dashed vertical lines represent the mean of the TO events. (b)-(e) Summary statistics of the 1stankle dorsiflexion peak (b) and its timing (c), and the 2ndankle plantarflexion peak (d) and its timing (e). The black horizontal lines indicate nonsignificant differences. 3.5 Pressure and pain feedback 266 The regions of pressure and pain reported by the participants are summarized in Table 1. The 267 most frequently mentioned regions were the hands for CR and the shank for ZG and IW. 268 4 Discussion 269 This study examined the effects of three different devices for unilateral foot/ankle unloading on 270 biomechanical, physiological, and subjective parameters measured during walking. Several studies 271 have previously examined the effects of axillary or forearm crutches and hands-free knee crutch, 272 such as IW. However, to the best of our knowledge, this is the first study to conduct a broad 273 scope of comprehensive biomechanical analysis, metabolic cost, and subjective evaluation of an 274 unloading AFO compared to other devices. Overall, the ZG AFO showed favorable results across 275 most parameters but performed poorly in terms of comfort. 276 4.1 Spatiotemporal, metabolic, and subjective parameters 277 Among the devices, the self-selected walking speed was significantly higher using ZG, but all 278 the devices exhibited significantly slower walking speed than NG (Fig. 2a). Similarly, previous 279 studies reported significantly slower walking using IW compared to NG [24, 34] and significantly 280 faster walking with IW compared to CR [35]. Contrary to our findings, other studies found that 281 participants walked slower with IW than with CR. However, they used axillary crutches [23, 34]. 282 We selected forearm crutches based on their overall superior performance over axillary crutches 283 reported in terms of walking speed, metabolic cost, and pressure on the upper extremities [5]. 284 Since the post-hoc results showed significant differences in self-selected walking speed between 285 the conditions, we conducted an additional statistical analysis with walking speed as a covariate 286 variable, to evaluate the effect of walking speed on the other variables. The results of this analysis 287 9 NG CR IW ZG20406080100[mm](b) Fluctuation Range NG CR IW ZG23456[%Height](d) Fluctuation Range Figure 6: Mediolateral and vertical components of the CoM. (a) Mediolateral CoM trajectories over the GC, with positive values indicating the direction of the loadbearing leg. (b) Summary statistics of the range of fluctuation of the mediolateral CoM. (c) Vertical CoM trajectories over the CG, normalized by the participants’ height. (d) Summary statistics of the vertical CoM range of fluctuation. In (a) and (c), the solid lines represent the median for each condition, the shaded domains represent the range of all cycles, and the dashed vertical lines represent the mean of the TO events. In (b) and (d), black horizontal lines indicate nonsignificant differences. are included in the supplementary file S1. Nevertheless, it is crucial to recognize that patients will 288 naturally adopt a self-selected walking speed in real-life clinical scenarios. Therefore, evaluating 289 parameter values without controlling for walking speed offers insights into the loads and motion 290 that patients genuinely experience and provides a relevant and practical perspective. 291 We found the highest metabolic cost while using CR, followed by IW, ZG, and NG, with 292 statistically significant differences between all pairs (Fig. 2b). The CR and IW results are consistent 293 with previous research [34, 35]. Moreover, these results correspond well with the participants’ rated 294 perceived exertion, which was significantly higher for CR, albeit comparable between IW and ZG. 295 These differences in perceived exertion ratings between CR and IW are consistent with previous 296 studies [23, 34]. The higher walking speed and lower metabolic cost of ZG support our hypothesis 297 that the ZG would lead to a more natural gait pattern, resulting in a faster and more energetically 298 efficient gait. 299 The significantly longer stance phase durations of the weight-bearing leg, observed using IW 300 and CR (Fig. 2c) are consistent with the difference in walking speed [36], and with previous research 301 [5, 24]. The participants may have increased the stance duration of their weight-bearing leg to 302 compensate for their lack of stability, as indicated by their stability ratings. The ZG exhibited 303 significantly higher stability rating and shorter stance phase than the other devices. Using CR and 304 IW, participants shortened the swing phase of the weight-bearing leg, subsequently shortening the 305 10 0 10 20 30 40 50 60 70 80 90 100 Stance phase (%)-50-30-1001030507090110130150 [%BW](a) NG CR IW ZGGRF- Vertical GRF- Anterior-Posterior NG CR IW ZG100120140160180(b) 1st Peak %BW NG CR IW ZG10152025(c) 1st Peak %SP NG CR IW ZG90100110120130(d) 2nd Peak %BW NG CR IW ZG-50-40-30-20-100(f) 1st Peak %BW NG CR IW ZG101520(g) 1st Peak %SP NG CR IW ZG7580859095(h) 2nd Peak %BW NG CR IW ZG1015202530(i) 2nd Peak %SPNG CR IW ZG406080100(e) 2nd Peak %SPVertical APFigure 7: Vertical and anterior-posterior (AP) components of the GRF normalized by body weight (BW). (a) The trajectories of the vertical and AP trajectories over the stance phase. The solid lines represent the medians and the shaded areas represent the range of all cycles. (b)-(i) Summary statistics of the different GRF peaks: (b) 1stpeak of vertical GRF, (c) timing of 1stvertical GRF, (d) 2ndpeak of vertical GRF, (e) timing of the 2ndpeak of vertical GRF, (f) 1stpeak of AP GRF, (g) timing of 1stpeak of AP GRF, (h) 2ndpeak of AP GRF, (i) timing of 2ndpeak of AP GRF. The black horizontal lines indicate nonsignificant differences. duration spent on the IW in single support and on the CR with no leg-ground contact, which are 306 unstable configurations. 307 11 Table 1: The ratings of pressure and pain locations on the unloaded leg indicated by the participants for each device. DeviceRated pressure Rated pain Region Number of participantsIntensity, Mean±SDRegion Number of participantsIntensity, Mean±SD CRHands 13 Hands 4 Forearm 3 Forearm 1 IWThigh 2 Thigh 2 Shank 7 Shank 3 ZGShank 19 Shank 12 Foot 6 Foot 6 4.2 Joint kinematics 308 All the devices altered the sagittal plane joint kinematics of the weight-bearing leg compared to 309 NG. However, the ZG resulted in a walking pattern that was overall more similar to NG in most 310 parameters. Particularly, hip extension (Fig. 3) at push-off was significantly reduced using IW (in 311 agreement with previous research [24]), contributing to a shorter stride length and reduced walking 312 speed. This is likely attributed to the challenge of swinging forward the leg fitted with the IW, 313 given its relatively heavy mass and the limitation to knee flexion, making ground clearance a more 314 challenging task. Using CR, the absence of hip extension was likely due to the forward inclination 315 of the upper body, assisted by the CR [8]. The hip angles using ZG were most similar to NG, 316 and the significant differences observed in the peak angles became nonsignificant once accounting 317 for walking speed as a covariate (see supplementary file S1). This suggests that the enabled knee 318 mobility on the affected side contributed to a more natural walking pattern on the weight-bearing 319 side. The significant delay in hip extension observed for all the devices is consistent with their 320 longer stance phase. 321 Similarly, the knee flexion angles of the weight-bearing leg were less affected by ZG than CR 322 and IW (Fig. 4). Particularly, CR caused a significantly larger knee flexion peak during stance, 323 in agreement with previously reported results [8], whereas IW and ZG did not alter this peak 324 significantly. However, after accounting for walking speed, the differences between NG-IW and 325 NG-ZG became significant (see supplementary file S1), which is consistent with previous findings 326 associating slower walking speed with reduced peak knee flexion during stance [37, 38]. The second 327 knee flexion peak, occurring during swing, was significantly lower using CR and IW (in agreement 328 with previous findings [24]), consistently with the shorter swing period and instability reported 329 with these devices. The use of ZG also reduced the peak of swing knee flexion, but significantly less 330 than the other devices. As with the hip angle, the delay observed in the second peak is consistent 331 with the delayed TO using the devices. 332 The effects of the devices on the weight-bearing ankle angles were less pronounced than the 333 other joints (Fig. 5). The dorsiflexion angle during stance was nonsignificantly altered by all 334 devices, and its delay was mainly due to the extended stance phase. Conversely, the push-off 335 12 plantarflexion was significantly reduced by the ZG, but not by the other devices. However, this 336 variable exhibited large variability, and when accounting for walking speed as a covariate, this 337 significance reversed. The reduced push-off plantarflexion could be related to the shoe leveler 338 worn on the weight-bearing leg during the ZG condition for equating the leg lengths. This may 339 have caused the participants to hesitate to fully plantarflex their ankle, since the shoe leveler 340 can slightly slip relative to the shoe. This difference can also explain the reduced push-off GRF 341 using the ZeroG. Additionally, the ZG AFO has a locked ankle joint and a relatively long and 342 flat sole, which might impair the initial roll-over motion of the affected leg occurring in parallel to 343 the weight-bearing leg’s plantarflexion peak. Conversely, the IW has a short and rounded contact 344 with the ground, which may have assisted in obtaining a more natural contralateral ankle push-off 345 movement. 346 4.3 Center of mass 347 Several significant differences have been identified in the patterns of the CoM (Fig. 6). The 348 increased mediolateral CoM fluctuation observed with the IW may have resulted from the inability 349 to flex the knee using IW, which required the participants to abduct their hips during swing 350 (circumduction) to achieve proper ground clearance. This movement, together with the relatively 351 large weight of the IW, required shifting of the CoM towards the unaffected leg, as evident in 352 6). In contrast, CR exhibited the smallest mediolateral CoM fluctuation, which indicates that the 353 participants used the CR’s contact with the ground to propel their body forward in a straighter 354 line. Although smaller mediolateral COM fluctuations may be attributed to improved balance, 355 the participants rated CR as the most unstable. 356 Regarding vertical CoM, CR resulted in a significantly larger fluctuation range than ZG and 357 IW, which exhibited fluctuations similar to NG. Note that the absolute values of IW and ZG are 358 higher. For IW, this could be attributed to the lack of knee flexion, and for ZG this is a result 359 of the added height of the device and the shoe leveler. Nevertheless, despite the higher CoMs, 360 their fluctuation ranges remained similar to NG. Minimizing CoM vertical fluctuation is commonly 361 thought to be related to minimized mechanical work and metabolic cost [39, 40], supporting our 362 findings. However, it is noted that the opposite hypothesis also prevails, but it refers to able-bodied 363 gait [41]. 364 4.4 Ground reaction forces 365 Several notable effects on the GRF patterns have been observed (Fig. 7). CR resulted in signif- 366 icantly higher braking GRFs in both vertical and posterior directions, consistent with previous 367 findings [12, 19]. This can be explained by the weight-bearing foot contacting the ground after a 368 short swing-through phase whereby the body accelerates forward, supported only by the crutches. 369 The abrupt brake of this acceleration likely led to the elevated GRF values and rates of change 370 (slope) seen for CR. These elevated peak forces and loading rates are even more prominent, con- 371 sidering that the walking speed was slower than in NG, for all devices. Since increased walking 372 speed is associated with increased GRFs [37, 42], these differences would likely increase if com- 373 pared at the same walking speed. This assumption is also supported by the statistical analysis 374 that includes walking speed as a covariate variable (see supplementary file S1). Increased braking 375 forces might be detrimental to the weight-bearing leg, particularly for patients with comorbidities. 376 In contrast, the lower GRF braking peaks obtained using ZG and IW may be beneficial in limiting 377 the risk of injury to the weight-bearing leg. The significant reduction in propulsive GRFs during 378 push-off (second peak) for ZG and IW could also be explained by the slower walking speed, as also 379 13 indicated by the nonsignificant differences from NG, when walking speed is taken as a covariate 380 (see supplementary file S1). 381 4.5 Summary and participant feedback 382 Overall, if we consider a smaller deviation from natural unassisted gait a positive indicator, the 383 ZG performed favorably in most metrics and could be viewed as a preferable alternative to CR 384 and IW. However, the pressure and pain feedback provided by the participants reveals that it 385 inflicted the most excessive pressure and pain, particularly on the shank region where the brace 386 is tightened. This suggests that the soft calf lacer of the ZG may be inadequate for complete 387 unloading, whereby the entire GRF is transferred through the shank. Instead, a rigid brace, 388 similar to an open transtibial prosthetic socket, may provide improved results [43]. However, a 389 rigid brace must be custom-made and not prefabricated. Furthermore, keeping the forefoot from 390 contacting the AFO sole during late stance was challenging, in agreement with previously reported 391 for patellar tendon bearing braces and casts [30, 44]. To avoid any contact between the forefoot 392 and the AFO base, we had to increase the height of the heel above the AFO base and support the 393 forefoot with a strap, which contributed to the discomfort reported by a few participants. The 394 CR and IW caused discomfort to fewer participants, mainly on the hands and shank, respectively, 395 aligning with previous reports [5, 23, 35]. Moreover, it is important to note that AFOs such as 396 the ZeroG require a significantly longer time, usually a few minutes, to be put on. Therefore, in 397 situations where quick assistance is needed for a short period of time, crutches may still be the 398 preferable option. 399 4.6 Limitations 400 This study encompasses several limitations. First, our study population was exclusively comprised 401 of young, healthy individuals. While the fact that the participants did not have an injured foot may 402 not significantly impact the results, given that the foot was completely unloaded during walking, 403 it restricts the generalizability of findings to broader populations. Moreover, it is worth noting 404 that this design allowed for the comparison of each parameter to the participant’s baseline. Future 405 research should explore the effects of these devices on older individuals and patients with diverse 406 injuries and pathologies. Second, we studied only walking at self-selected speed on level ground, 407 whereas a rehabilitation process typically includes other activities of daily living, such as walking 408 on uneven and inclined surfaces, stair ascent and descent, sit-to-stand, and more. Furthermore, 409 additional biomechanical parameters, such as joint kinematics and kinetics in the transverse and 410 coronal planes, and plantar pressure, should also be examined. 411 4.7 Impact 412 Using assistive devices in situations that require unloading can provide valuable benefits across 413 diverse domains, such as enhancing mobility, supporting independence, facilitating active partic- 414 ipation in daily life, encouraging physical activity, and enhancing cardiovascular and metabolic 415 health [42]. Choosing the right device plays a key role in maintaining functionality and mitigating 416 adverse effects on the affected leg (e.g., muscle atrophy and bone density reduction in the proximal 417 leg regions that can be mobilized and loaded), as well as the weight-bearing leg and upper body 418 (e.g., nerve compression and fractures). Additionally, maintaining a more even weight distribution 419 and natural gait pattern may lead to a shorter acclimation period with the device and enhanced 420 safety and balance, although this still needs to be verified in future clinical studies. 421 14 Achieving consistent and proper adherence to offloading devices remains a challenge, particu- 422 larly in diabetic foot ulcers [45]. To optimize their impact, it is crucial to understand how these 423 devices affect biomechanics, energy consumption, and user experience. Informing healthcare pro- 424 fessionals about the different multi-factorial effects of each device can help them choose the best 425 device for a particular patient. Moreover, the insights gained from this study can lead to ad- 426 vancements in device design, overcoming the identified limitations, and resulting in improved user 427 satisfaction and clinical effectiveness, thereby maximizing their impact in real-world healthcare 428 scenarios. 429 5 Conclusion 430 In summary, this study aimed to investigate the effect of three different devices for foot-ankle 431 unloading on walking biomechanics, metabolic cost, and preference. Significant differences among 432 the devices were identified across all parameters, with results from crutches and iWalk aligning with 433 previous studies. The ZeroG demonstrated favorable performance in most aspects, highlighting 434 the potential of AFOs in enhancing gait rehabilitation when unloading is necessary. However, 435 ZeroG’s shortcomings in terms of comfort and sound-side ankle kinematics were evident. 436 These findings may offer valuable insights for researchers and clinicians, which could aid in 437 informed decision-making regarding the prescription of such devices for patients with foot-ankle 438 injuries and pathologies. Furthermore, future work may leverage these results toward the design 439 of enhanced ankle-foot unloading devices that improve rehabilitation and patient care. 440 6 List of abbreviations 441 •6MWT: 6 Minute Walk Test 442 •AFO: Ankle Foot Orthosis 443 •BW: Body Weight 444 •CoM: Center of Mass 445 •CR: Crutches 446 •IC: Initial Contact 447 •IW: iWalk 448 •NG: Normal Gait 449 •SP: Stance Phase 450 •TO: Toe Off 451 •ZG: ZeroG 452 15 7 Declarations 453 7.1 Ethics approval and consent to participate 454 The study was approved by the Institutional Review Board at Technion (#108-2020). Before their 455 inclusion and following a detailed explanation of the study requirements, participants provided 456 written informed consent. 457 7.2 Consent for publication 458 Individual participant’s data are used with informed consent. 459 7.3 Availability of data and materials 460 The datasets used and/or analysed during the current study are available from the corresponding 461 author on reasonable request. 462 7.4 Competing interests 463 The authors declare that they have no competing interests. 464 7.5 Funding 465 Not Applicable. 466 7.6 Authors’ contributions 467 Conceptualization: D.S. Data acquisition: E.S., E.I., and Y.T. Data processing: E.S., E.I., and 468 Y.T. Data interpretation: E.S., E.I., Y.T., E.K., and D.S. Manuscript draft: E.S., E.I., and 469 D.S. Manuscript revisions: E.S., E.I., Y.T., E.K., Y.E., and D.S. All authors approved the final 470 manuscript. 471 7.7 Acknowledgements 472 The authors would like to thank the study participants for their time and dedication. 473