Surfaces Decorated with Enantiomorphically Pure Polymer Nanohelices via Hierarchical Chirality Transfer across Multiple Length Scales.

Mesoscale chiral materials are prepared by lithographic methods, assembly of chiral building blocks, and through syntheses in the presence of polarized light. Typically, these processes result in micrometer-sized structures, require complex top-down manipulation, or rely on tedious asymmetric separation. Chemical vapor deposition (CVD) polymerization of chiral precursors into supported films of liquid crystals (LCs) are discovered to result in superhierarchical arrangements of enantiomorphically pure nanofibers. Depending on the molecular chirality of the 1-hydroxyethyl [2.2]paracyclophane precursor, extended arrays of enantiomorphic nanohelices are formed from achiral nematic templates. Arrays of chiral nanohelices extend over hundreds of micrometers and consistently display enantiomorphic micropatterns. The pitch of individual nanohelices depends on the enantiomeric excess and the purity of the chiral precursor, consistent with the theoretical model of a doubly twisted LC director configuration. During CVD of chiral precursors into cholesteric LC films, aspects of molecular and mesoscale asymmetry combine constructively to form regularly twisted nanohelices. Enantiomorphic surfaces permit the tailoring of a wide range of functional properties, such as the asymmetric induction of weak chiral systems.

Templated nanofiber synthesis via chemical vapor polymerization into liquid crystalline films.

Extrusion, electrospinning, and microdrawing are widely used to create fibrous polymer mats, but these approaches offer limited access to oriented arrays of nanometer-scale fibers with controlled size, shape, and lateral organization. We show that chemical vapor polymerization can be performed on surfaces coated with thin films of liquid crystals to synthesize organized assemblies of end-attached polymer nanofibers. The process uses low concentrations of radical monomers formed initially in the vapor phase and then diffused into the liquid-crystal template. This minimizes monomer-induced changes to the liquid-crystal phase and enables access to nanofiber arrays with complex yet precisely defined structures and compositions. The nanofiber arrays permit tailoring of a wide range of functional properties, including adhesion that depends on nanofiber chirality.

Development and Evaluation of a Kinect-based Rapid Movement Therapy Training Platform for Balance Rehabilitation.

With the growing aging and overall population, the demand for healthcare professionals and their burden increases by time. Effective balance recovery reaction is required to prevent falls. The aim of this project is to provide low-cost portable balance training system that trains the two important components of effective balance recovery reaction: faster movement completion time (MT) and larger range of motion (ROM). This is done by a Kinect-based interactive rapid movement therapy training platform for reaching and stepping actions. The platform provides real-time feedback to the patient, generates a report for healthcare professionals to monitor the patient's progress, and can be utilized in patient's home or community centers. A pilot study to test the platform was conducted on seventeen stroke patients and it has shown significant improvement in both MT (faster) and ROM (larger).

Micropatterned Scaffolds with Immobilized Growth Factor Genes Regenerate Bone and Periodontal Ligament-Like Tissues.

Periodontal disease destroys supporting structures of teeth. However, tissue engineering strategies offer potential to enhance regeneration. Here, the strategies of patterned topography, spatiotemporally controlled growth factor gene delivery, and cell-based therapy to repair bone-periodontal ligament (PDL) interfaces are combined. Micropatterned scaffolds are fabricated for the ligament regions using polycaprolactone (PCL)/polylactic-co-glycolic acid and combined with amorphous PCL scaffolds for the bone region. Scaffolds are modified using chemical vapor deposition, followed by spatially controlled immobilization of vectors encoding either platelet-derived growth factor-BB or bone morphogenetic protein-7, respectively. The scaffolds are seeded with human cells and delivered to large alveolar bone defects in athymic rats. The effects of dual and single gene delivery with and without micropatterning are assessed after 3, 6, and 9 weeks. Gene delivery results in greater bone formation at three weeks. Micropatterning results in regenerated ligamentous tissues similar to native PDL. The combination results in more mature expression of collagen III and periostin, and with elastic moduli of regenerated tissues that are statistically indistinguishable from those of native tissue, while controls are less stiff than native tissues. Thus, controlled scaffold microtopography combined with localized growth factor gene delivery improves the regeneration of periodontal bone-PDL interfaces.

Backbone-Degradable Polymers Prepared by Chemical Vapor Deposition.

Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has limited wider applicability in many areas, such as biomedical devices or regenerative medicine. Herein, we demonstrate, for the first time, a backbone-degradable polymer directly synthesized via CVD. The CVD co-polymerization of [2.2]para-cyclophanes with cyclic ketene acetals, specifically 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), results in well-defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry. The degradation kinetics are dependent on the ratio of ketene acetals to [2.2]para-cyclophanes as well as the hydrophobicity of the films. These coatings address an unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability.

Multigrowth Factor Delivery via Immobilization of Gene Therapy Vectors.

Molecules can be immobilized onto biomaterials by a chemical vapor deposition (CVD) coating strategy. Pentafluorophenolester groups react with amine side chains on antibodies, which can selectively immobilize adenoviral vectors for gene delivery of growth factors. These vectors can produce functional proteins within defined regions of biomaterials to produce customizable structures for targeted tissue regeneration.

Acquiring visual information for locomotion by older adults: a systematic review.

Developments in technology have facilitated quantitative examination of gaze behavior in relation to locomotion. The objective of this systematic review is to provide a critical evaluation of available evidence and to explore the role of gaze behavior among older adults during different forms of locomotion. Database searches were conducted to identify research papers that met the inclusion criteria of (1) study variables that included direct measurement of gaze and at least one form of locomotion, (2) participants who were older adults aged 60 years and above, and (3) reporting original research. Twenty-five papers related to walking on a straight path and turning (n=4), stair navigation (n=3), target negotiation and obstacle circumvention (n=13) and perturbation-evoked sudden loss of balance (n=5) were identified for the final quality assessment. The reviewed articles were found to have acceptable quality, with scores ranging from 47.06% to 94.12%. Overall, the current literature suggests that differences in gaze behavior during locomotion appear to change in late adulthood, especially with respect to transfer of gaze to and from a target, saccade-step latency, fixation durations on targets and viewing patterns. These changes appear to be particularly pronounced for older adults with high risk of falling and impaired executive functioning.

Footwear width and balance-recovery reactions: A new approach to improving lateral stability in older adults.

BACKGROUND: Age-related difficulty in controlling lateral stability is of crucial importance because lateral falls increase risk of debilitating hip-fracture injury. This study examined whether a small increase in footwear sole width can improve ability of older adults to regain lateral stability subsequent to balance perturbation. METHODS: The study involved sixteen healthy, ambulatory, community-dwelling older adults (aged 65-78). Widened base-of-support (WBOS) footwear was simulated by affixing polystyrene-foam blocks (20mm wide) on the medial and lateral sides of rubber overshoes; unaltered overshoes were worn in normal (NBOS) trials. Balance perturbations were applied using a motion platform. RESULTS: Gait, mobility and agility tests revealed no adverse effects of wearing the WBOS footwear. Lateral-perturbation tests showed that the WBOS footwear improved ability to stabilize the body without stepping (p=0.002). Depending on the perturbation magnitude, the frequency of stepping was reduced by up to 25% (64% of NBOS trials vs 39% of WBOS trials). In addition, the WBOS footwear appeared to improve ability to maintain lateral stability during forward-step reactions, as evidenced by reduced incidence of additional lateral steps (p=0.04) after stepping over an obstacle in response to a forward-fall perturbation. CONCLUSIONS: A small increase in sole width can improve certain aspects of lateral stability in older adults, without compromising mobility and agility. This finding supports the viability of WBOS footwear as an intervention to improve balance. Further research is needed to test populations with more severe balance impairments, examine user compliance, and determine if WBOS footwear actually reduces falling risk in daily life.

Evaluation of the Microsoft Kinect as a clinical assessment tool of body sway.

Total body center of mass (TBCM) is a useful kinematic measurement of body sway. However, expensive equipment and high technical requirement limit the use of motion capture systems in large-scale clinical settings. Center of pressure (CP) measurement obtained from force plates cannot accurately represent TBCM during large body sway movement. Microsoft Kinect is a rapidly developing, inexpensive, and portable posturographic device, which provides objective and quantitative measurement of TBCM sway. The purpose of this study was to evaluate Kinect as a clinical assessment tool for TBCM sway measurement. The performance of the Kinect system was compared with a Vicon motion capture system and a force plate. Ten healthy male subjects performed four upright quiet standing tasks: (1) eyes open (EOn), (2) eyes closed (ECn), (3) eyes open standing on foam (EOf), and (4) eyes closed standing on foam (ECf). Our results revealed that the Kinect system produced highly correlated measurement of TBCM sway (mean RMSE=4.38 mm; mean CORR=0.94 in Kinect-Vicon comparison), as well as comparable intra-session reliability to Vicon. However, the Kinect device consistently overestimated the 95% CL of sway by about 3mm. This offset could be due to the limited accuracy, resolution, and sensitivity of the Kinect sensors. The Kinect device was more accurate in the medial-lateral than in the anterior-posterior direction, and performed better than the force plate in more challenging balance tasks, such as (ECf) with larger TBCM sway. Overall, Kinect is a cost-effective alternative to a motion capture and force plate system for clinical assessment of TBCM sway.

Do aging and dual-tasking impair the capacity to store and retrieve visuospatial information needed to guide perturbation-evoked reach-to-grasp reactions?

A recent study involving young adults showed that rapid perturbation-evoked reach-to-grasp balance-recovery reactions can be guided successfully with visuospatial-information (VSI) retained in memory despite: 1) a reduction in endpoint accuracy due to recall-delay (time between visual occlusion and perturbation-onset, PO) and 2) slowing of the reaction when performing a concurrent cognitive task during the recall-delay interval. The present study aimed to determine whether this capacity is compromised by effects of aging. Ten healthy older adults were tested with the previous protocol and compared with the previously-tested young adults. Reactions to recover balance by grasping a small handhold were evoked by unpredictable antero-posterior platform-translation (barriers deterred stepping reactions), while using liquid-crystal goggles to occlude vision post-PO and for varying recall-delay times (0-10 s) prior to PO (the handhold was moved unpredictably to one of four locations 2 s prior to vision-occlusion). Subjects also performed a spatial- or non-spatial-memory cognitive task during the delay-time in a subset of trials. Results showed that older adults had slower reactions than the young across all experimental conditions. Both age groups showed similar reduction in medio-lateral end-point accuracy when recall-delay was longest (10 s), but differed in the effect of recall delay on vertical hand elevation. For both age groups, engaging in either the non-spatial or spatial-memory task had similar (slowing) effects on the arm reactions; however, the older adults also showed a dual-task interference effect (poorer cognitive-task performance) that was specific to the spatial-memory task. This provides new evidence that spatial working memory plays a role in the control of perturbation-evoked balance-recovery reactions. The delays in completing the reaction that occurred when performing either cognitive task suggest that such dual-task situations in daily life could increase risk of falling in seniors, particularly when combined with the general age-related slowing that was observed across all experimental conditions.

Effects of spatial-memory decay and dual-task interference on perturbation-evoked reach-to-grasp reactions in the absence of online visual feedback.

Recent findings suggest that rapid perturbation-evoked reach-to-grasp balance-recovery reactions can be (and often are) guided by visuospatial information stored in working memory. To further our understanding, the present study examined the influence of memory-decay and concurrent cognitive-task performance on the speed, accuracy and effectiveness of these reactions by using liquid-crystal goggles to initiate occlusion of vision at various "recall-delay" times prior to perturbation-onset, in ten healthy young-adults. A small handhold was moved unpredictably to one of four locations 2s prior to vision-occlusion; reactions to recover balance by grasping the handhold were evoked by unpredictable antero-posterior platform-translation perturbations. Recall-delay time (0s/2s/5s/10s) was randomized, and subjects performed a spatial- or non-spatial-memory task during the delay-time in a subset of trials. Consistent with studies of volitional reach-to-grasp, recall-delay led to some reduction in endpoint accuracy; however, unlike those studies, the present results showed no evidence that recall-delay led to slowing of the arm movement. Both spatial and non-spatial cognitive tasks had similar effects (slowing of movement initiation and execution), suggesting these effects were related to generic attentional demands rather than competition for specific resources related to spatial working memory. Further work is needed to determine effects of age-related impairments in visuospatial memory and attentional capacity.

Does aging impair the capacity to use stored visuospatial information or online visual control to guide reach-to-grasp reactions evoked by unpredictable balance perturbation?

BACKGROUND: Rapid reach-to-grasp reactions are a prevalent response to sudden loss of balance and play an important role in preventing falls. A previous study indicated that young adults are able to guide functionally effective grasping reactions using visuospatial information (VSI) stored in working memory. The present study addressed whether healthy older adults are also able to use "stored" VSI in this manner or are more dependent on "online" visual control. METHODS: Liquid-crystal goggles were used to force reliance on either stored or online VSI while reaching to grasp a small handhold in response to unpredictable platform perturbations. A motor-driven device varied the handhold location unpredictably for each trial. Twelve healthy older adults (65-79 years) were compared with 12 young adults (19-29 years) tested in a previous study. RESULTS: Reach-to-grasp reactions were slower and more variable in older adults, regardless of the nature of the available VSI. When forced to rely on stored VSI, both age groups showed a reduction in reach accuracy; however, a tendency to undershoot the handhold was exacerbated in the older adults. Forced reliance on online VSI led to similar delays in both age groups; however, the older adults were more likely to reach with the "wrong" limb (contralateral to the handhold) and/or raise both arms initially (possibly to "buy" more time for final limb selection). CONCLUSION: Situations that force the central nervous system to rely on either stored or online VSI tend to exacerbate age-related reductions in speed and accuracy of reach-to-grasp balance-recovery reactions. Further work is needed to determine if this increases risk of falling in daily life.

Reaching to recover balance in unpredictable circumstances: is online visual control of the reach-to-grasp reaction necessary or sufficient?

Reaching to grasp an object for support is a common and functionally important response to sudden balance perturbation. The need to react very rapidly (to prevent falling) imposes temporal constraints on acquisition and processing of the visuospatial information (VSI) needed to guide the reaching movement. Previous results suggested that the CNS may deal with these constraints by using VSI stored in memory proactively, prior to perturbation onset; however, the extent to which online visual control is necessary or sufficient to guide these reactions has not been established. This study examined the speed, accuracy, and effectiveness of perturbation-evoked reach-to-grasp reactions when forced to rely entirely on either online- or stored-VSI by using liquid-crystal goggles to occlude vision either before or after perturbation onset. The reactions were evoked, in twelve healthy young adults, via sudden unpredictable antero-posterior platform translation (barriers deterred stepping reactions). Prior to perturbation onset, a small cylindrical handhold was positioned unpredictably (by a motor-driven device) at one of four locations in front of the subject. Results indicated that equilibrium could be recovered successfully by grasping the handhold using either online-VSI or stored-VSI to guide the arm reaction; however, both sources of VSI were required for optimal performance. Reach initiation and arm movement were slowed when dependent on online-VSI, whereas reach accuracy and grip formation were impaired when dependent on stored-VSI. Comparison with normal-VSI trials suggests that both sources of VSI are utilized when grasping a small handhold for support under normal visual conditions, with stored-VSI predominating during initiation/transport and online-VSI contributing primarily to final target acquisition/prehension.

The use of peripheral vision to guide perturbation-evoked reach-to-grasp balance-recovery reactions.

For a reach-to-grasp reaction to prevent a fall, it must be executed very rapidly, but with sufficient accuracy to achieve a functional grip. Recent findings suggest that the CNS may avoid potential time delays associated with saccade-guided arm movements by instead relying on peripheral vision (PV). However, studies of volitional arm movements have shown that reaching is slower and/or less accurate when guided by PV, rather than central vision (CV). The present study investigated how the CNS resolves speed-accuracy trade-offs when forced to use PV to guide perturbation-evoked reach-to-grasp balance-recovery reactions. These reactions were evoked, in 12 healthy young adults, via sudden unpredictable antero-posterior platform translation (barriers deterred stepping reactions). In PV trials, subjects were required to look straight-ahead at a visual target while a small cylindrical handhold (length 25%> hand-width) moved intermittently and unpredictably along a transverse axis before stopping at a visual angle of 20°, 30°, or 40°. The perturbation was then delivered after a random delay. In CV trials, subjects fixated on the handhold throughout the trial. A concurrent visuo-cognitive task was performed in 50% of PV trials but had little impact on reach-to-grasp timing or accuracy. Forced reliance on PV did not significantly affect response initiation times, but did lead to longer movement times, longer time-after-peak-velocity and less direct trajectories (compared to CV trials) at the larger visual angles. Despite these effects, forced reliance on PV did not compromise ability to achieve a functional grasp and recover equilibrium, for the moderately large perturbations and healthy young adults tested in this initial study.

The moveable handhold: a new paradigm to study visual contributions to the control of balance-recovery reactions.

Balance-recovery reactions that involve rapid step or reach-to-grasp movements are prevalent and functionally important responses to instability. Successful use of these reactions to recover balance in daily life requires a capacity to modulate the reaction to deal with the continual variation in environmental constraints that occurs as the person moves, i.e. location of objects that can obstruct limb movements or serve as handholds to grasp. The most direct approach to study this involves applying balance perturbations as subjects move within a visually complex environment; however, this approach does not allow precise control over kinematic variables or visual inputs, and is susceptible to strong learning effects. We have therefore developed an alternate approach, wherein the subject is stationary and the relative motion between subject and constraints that normally occurs as a result of ambulation is instead introduced via movement of the surrounding obstacles or handholds. We previously developed a motor-driven "obstacle-mover" to manipulate constraints on step reactions, and now describe an analogous approach to study reach-to-grasp reactions, using a motor-driven "handhold-mover". We anticipate that this paradigm will provide new opportunities to probe CNS control of upright stance, by providing a sensitive indicator of limitations in the neuromusculoskeletal systems. It can also be used to test perturbation-evoked reactions in seated subjects, thereby allowing testing or training of persons who are unable to stand and use of techniques (e.g. TMS, EEG) that can be difficult to perform in free-standing subjects.

Preventing falls in older adults: new interventions to promote more effective change-in-support balance reactions.

"Change-in-support" (CIS) balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls; however, age-related deficits in the neuro-musculoskeletal systems may impede ability to execute these reactions effectively. This review describes four new interventions aimed at reducing fall risk in older adults by promoting more effective CIS reactions: (1) balance training, (2) balance-enhancing footwear, (3) safer mobility aids, and (4) handrail cueing systems. The training program uses unpredictable support-surface perturbations to counter specific CIS control problems associated with aging and fall risk. Pilot testing has demonstrated that the program is well-tolerated by balance-impaired older adults, and a randomized controlled trial is now in progress. The balance-enhancing footwear insole improves control of stepping reactions by compensating for age-related loss of plantar cutaneous sensation. In a clinical trial, subjects wore the insole for 12 weeks with no serious problems and no habituation of the balance-enhancing benefits. The mobility-aid intervention involves changes to the design of pickup walkers so as to reduce impediments to lateral stepping. Finally, work is underway to investigate the effectiveness of handrail cueing in attracting attention to the rail and ensuring that the brain registers its location, thereby facilitating more rapid and accurate grasping.