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1.  Comparison of Cellular Architecture, Axonal Growth, and Blood Vessel Formation Through Cell-Loaded Polymer Scaffolds in the Transected Rat Spinal Cord 
Tissue Engineering. Part A  2014;20(21-22):2985-2997.
The use of multichannel polymer scaffolds in a complete spinal cord transection injury serves as a deconstructed model that allows for control of individual variables and direct observation of their effects on regeneration. In this study, scaffolds fabricated from positively charged oligo[poly(ethylene glycol)fumarate] (OPF+) hydrogel were implanted into rat spinal cords following T9 complete transection. OPF+ scaffold channels were loaded with either syngeneic Schwann cells or mesenchymal stem cells derived from enhanced green fluorescent protein transgenic rats (eGFP-MSCs). Control scaffolds contained extracellular matrix only. The capacity of each scaffold type to influence the architecture of regenerated tissue after 4 weeks was examined by detailed immunohistochemistry and stereology. Astrocytosis was observed in a circumferential peripheral channel compartment. A structurally separate channel core contained scattered astrocytes, eGFP-MSCs, blood vessels, and regenerating axons. Cells double-staining with glial fibrillary acid protein (GFAP) and S-100 antibodies populated each scaffold type, demonstrating migration of an immature cell phenotype into the scaffold from the animal. eGFP-MSCs were distributed in close association with blood vessels. Axon regeneration was augmented by Schwann cell implantation, while eGFP-MSCs did not support axon growth. Methods of unbiased stereology provided physiologic estimates of blood vessel volume, length and surface area, mean vessel diameter, and cross-sectional area in each scaffold type. Schwann cell scaffolds had high numbers of small, densely packed vessels within the channels. eGFP-MSC scaffolds contained fewer, larger vessels. There was a positive linear correlation between axon counts and vessel length density, surface density, and volume fraction. Increased axon number also correlated with decreasing vessel diameter, implicating the importance of blood flow rate. Radial diffusion distances in vessels significantly correlated to axon number as a hyperbolic function, showing a need to engineer high numbers of small vessels in parallel to improving axonal densities. In conclusion, Schwann cells and eGFP-MSCs influenced the regenerating microenvironment with lasting effect on axonal and blood vessel growth. OPF+ scaffolds in a complete transection model allowed for a detailed comparative, histologic analysis of the cellular architecture in response to each cell type and provided insight into physiologic characteristics that may support axon regeneration.
PMCID: PMC4229864  PMID: 24854680
2.  Assembly of Protein-Based Hollow Spheres Encapsulating a Therapeutic Factor 
ACS Chemical Neuroscience  2013;4(9):1297-1304.
Neurotrophins, as important regulators of neural development, function, and survival, have a therapeutic potential to repair damaged neurons. However, a controlled delivery of therapeutic molecules to injured tissue remains one of the greatest challenges facing the translation of novel drug therapeutics field. This study presents the development of an innovative protein–protein delivery technology of nerve growth factor (NGF) by an electrostatically assembled protein-based (collagen) reservoir system that can be directly injected into the injury site and provide long-term release of the therapeutic. A protein-based biomimetic hollow reservoir system was fabricated using a template method. The capability of neurotrophins to localize in these reservoir systems was confirmed by confocal images of fluorescently labeled collagen and NGF. In addition, high loading efficiency of the reservoir system was proven using ELISA. By comparing release profile from microspheres with varying cross-linking, highly cross-linked collagen spheres were chosen as they have the slowest release rate. Finally, biological activity of released NGF was assessed using rat pheochromocytoma (PC12) cell line and primary rat dorsal root ganglion (DRG) cell bioassay where cell treatment with NGF-loaded reservoirs induced significant neuronal outgrowth, similar to that seen in NGF treated controls. Data presented here highlights the potential of a high capacity reservoir-growth factor technology as a promising therapeutic treatment for neuroregenerative applications and other neurodegenerative diseases.
PMCID: PMC3778428  PMID: 23763540
Biomaterials; spheres; neural tissue engineering; neural regeneration; capsules; neurotrophins; nerve growth factor; drug delivery; dorsal root ganglia
3.  Design and evaluation of theory-informed technology to augment a wellness motivation intervention 
Integrating mobile technology into health promotion strategies has the potential to support healthy behaviors. A new theory-informed app was designed to augment an intervention promoting wellness motivation in older adults with fall risk and low levels of physical activity. The app content was evaluated for clarity, homogeneity, and validity of motivational messages; both the app and device were evaluated for acceptability and usability. The initial evaluation included nine adults (mean age, 75); four of whom also assessed the app’s sensing abilities in the field. As part of an intervention feasibility study, 14 older adults (mean age, 84) also provided a follow-up evaluation of app usability. Evaluation participants assessed the app as valid, usable, acceptable, and able to sense most reported free-living activities, and provided feedback for improving the app. Design processes illustrate methodologic and interpretive efforts to operationalize motivational content in a theory-informed app promoting change in physical activity behavior.
PMCID: PMC3958597  PMID: 24653780
Mobile health; Technology-supporting behavior change; Design; Persuasive technology; iOS accelerometer; Self-monitoring; Older adults; Physical activity; Health behavior intervention; Wellness motivation intervention; Behavior change technologies
4.  External Validity of Physical Activity Interventions for Community-Dwelling Older Adults with Fall Risk: A Quantitative Systematic Literature Review 
Journal of advanced nursing  2012;68(10):2140-2154.
To appraise the external validity of physical activity interventions designed to reduce falls among community-dwelling older adults, using the reach, efficacy/effectiveness, adoption, implementation, and maintenance framework.
Falls are a globally common, significant, and preventable problem. The efficacy of physical activity interventions to reduce falls among older adults is well established. Translation of this research into practice is slow as evidenced by persistently low proportions of older adults who engage in physical activities and the rising incidence of falls.
Data Sources
Four electronic databases were searched for relevant studies published between 2000 and 2010. Studies that examined the effects of physical activity interventions designed to reduce falls among community dwelling older adults were included in this review (n = 46).
Review Methods
This was a quantitative systematic review with narrative synthesis. The reach, efficacy/effectiveness, adoption, implementation, and maintenance framework guided the identification, appraisal, and synthesis of indicators representing study validity.
The majority of studies in this review described indicators representing internal validity. Details about indicators representing external validity were reported infrequently, limiting the generalizability of fall-preventive physical activity interventions in diverse cultures and social contexts over time.
To foster translational research in real world settings, additional programmatic intervention research is needed that: (a) targets diverse populations; (b) incorporates theories of behavioural change; (c) describes and operationalizes critical content that enables replication and translation; (d) tests innovative measures of fall risk and physical activity; and (e) evaluates feasibility and acceptability.
PMCID: PMC3463998  PMID: 22416905
falls; fall prevention; physical activity interventions; older adults; systematic review; nursing
5.  Wellness in Older Adults: A Concept Analysis 
Nursing Forum  2012;47(1):39-51.
PMCID: PMC3326391  PMID: 22309381
6.  Practice Development Section Paper 1 Older People’s Perspectives on Fall Risk and Fall Prevention Programs: A Literature Review 
Despite evidence supporting fall prevention methods, fall-related injury and death rates continue to rise. Understanding older people’s views on fall risk and prevention will help nurses and other health professionals in the design of fall prevention strategies that will broaden their scope, reach, and adoption. This literature review synthesized 19 qualitative and quantitative studies examining older people’s perspectives about fall risk and prevention using a social ecological framework. Three themes emerged about fall risk; fearing vulnerability, maintaining autonomy and independence, and interpreting risk. Four themes emerged about fall prevention programs; influence of participant and program characteristics, need for personal relevance and preference, maintaining autonomy and independence, and increased support for and access to programs. Implications for practice include individual, interpersonal, organizational and community level considerations for improving fall prevention efforts.
PMCID: PMC3268078  PMID: 22078019
Falls; Health Promotion; Person-Centred Practice
7.  ReadySteady: App for Accelerometer-based Activity Monitoring and Wellness-Motivation Feedback System for Older Adults 
Increased physical activity and exercise have been found to reduce falls and decrease mortality and age-related morbidity in older adults. However, a large percentage of this population fail to achieve the necessary levels of activity needed to support health living. In this work, we present a mobile app developed on the iOS platform that monitors activity levels using accelerometry. The data captured by the sensor is utilized to provide real-time motivational feedback to enable reinforcement of positive behaviors in older adults. Pilot experiments (conducted with younger adults) performed to assess validity of activity measurement showed that system accurately measures sedentary, light, moderate and vigorous activities in a controlled lab setting. Pilot tests (conducted with older adults) in the user setting showed that while the app is adept at capturing gross body activity (such as sitting, walking and jogging), additional sensors may be required to capture activities involving the extremities.
PMCID: PMC3540520  PMID: 23304368
8.  Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds☆ 
This review highlights current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury. The concept of developing 3-dimensional polymer scaffolds for placement into a spinal cord transection model has recently been more extensively explored as a solution for restoring neurologic function after injury. Given the patient morbidity associated with respiratory compromise, the discrete tracts in the spinal cord conveying innervation for breathing represent an important and achievable therapeutic target. The aim is to derive new neuronal tissue from the surrounding, healthy cord that will be guided by the polymer implant through the injured area to make functional reconnections. A variety of naturally derived and synthetic biomaterial polymers have been developed for placement in the injured spinal cord. Axonal growth is supported by inherent properties of the selected polymer, the architecture of the scaffold, permissive microstructures such as pores, grooves or polymer fibres, and surface modifications to provide improved adherence and growth directionality. Structural support of axonal regeneration is combined with integrated polymeric and cellular delivery systems for therapeutic drugs and for neurotrophic molecules to regionalize growth of specific nerve populations.
PMCID: PMC2981799  PMID: 19737633
Spinal cord injury; Axonal regeneration; Polymer scaffold; Tissue engineering; Neurotrophins

Results 1-8 (8)