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New method for the isolation of endothelial cells from large vessels

Ataollahi F, Pingguan-Murphy B, Moradi A, Wan Abas WA, Chua KH, Abu Osman NA

Cytotherapy, 2014 Aug;16(8):1145-52.
PMID: 24831838 DOI: 10.1016/j.jcyt.2014.01.010

Numerous protocols for the isolation of bovine aortic endothelial cells have been described in the previous literature. However, these protocols prevent researchers from obtaining the pure population of endothelial cells. Thus, this study aimed to develop a new and economical method for the isolation of pure endothelial cells by introducing a new strategy to the enzymatic digestion method proposed by previous researchers.
Endothelial cell responses in terms of adhesion, proliferation, and morphology to stiffness of polydimethylsiloxane elastomer substrates

Ataollahi F, Pramanik S, Moradi A, Dalilottojari A, Pingguan-Murphy B, Wan Abas WA, et al.

J Biomed Mater Res A, 2015 Jul;103(7):2203-13.
PMID: 24733741 DOI: 10.1002/jbm.a.35186

Extracellular environments can regulate cell behavior because cells can actively sense their mechanical environments. This study evaluated the adhesion, proliferation and morphology of endothelial cells on polydimethylsiloxane (PDMS)/alumina (Al2 O3 ) composites and pure PDMS. The substrates were prepared from pure PDMS and its composites with 2.5, 5, 7.5, and 10 wt % Al2 O3 at a curing temperature of 50°C for 4 h. The substrates were then characterized by mechanical, structural, and morphological analyses. The cell adhesion, proliferation, and morphology of cultured bovine aortic endothelial (BAEC) cells on substrate materials were evaluated by using resazurin assay and 1,1'-dioctadecyl-1,3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated LDL (Dil-Ac-LDL) cell staining, respectively. The composites (PDMS/2.5, 5, 7.5, and 10 wt % Al2 O3 ) exhibited higher stiffness than the pure PDMS substrate. The results also revealed that stiffer substrates promoted endothelial cell adhesion and proliferation and also induced spread morphology in the endothelial cells compared with lesser stiff substrates. Statistical analysis showed that the effect of time on cell proliferation depended on stiffness. Therefore, this study concludes that the addition of different Al2 O3 percentages to PDMS elevated substrate stiffness which in turn increased endothelial cell adhesion and proliferation significantly and induced spindle shape morphology in endothelial cells.
Modelling the mechanical response of skin in vivo using the Bossinesq and the Michell stress functions

Wan Abas WA, Asseli MR

Biomed Mater Eng, 1994;4(7):463-71.
PMID: 7881330

Local strains acting across an area of skin loaded uniaxially in vivo are converted to stresses using the standard elastic formulae. The stress values are compared to those obtained using the classical Bossinesq and Michell stress functions. The results indicate that these functions are capable of describing the response of the skin, both in the low load and the high load regions.
Finite element analysis on longitudinal and radial functionally graded femoral prosthesis

Oshkour AA, Abu Osman NA, Davoodi MM, Yau YH, Tarlochan F, Wan Abas WA, et al.

Int J Numer Method Biomed Eng, 2013 Dec;29(12):1412-27.
PMID: 23922316 DOI: 10.1002/cnm.2583

This study focused on developing a 3D finite element model of functionally graded femoral prostheses to decrease stress shielding and to improve total hip replacement performance. The mechanical properties of the modeled functionally graded femoral prostheses were adjusted in the sagittal and transverse planes by changing the volume fraction gradient exponent. Prostheses with material changes in the sagittal and transverse planes were considered longitudinal and radial prostheses, respectively. The effects of cemented and noncemented implantation methods were also considered in this study. Strain energy and von Mises stresses were determined at the femoral proximal metaphysis and interfaces of the implanted femur components, respectively. Results demonstrated that the strain energy increased proportionally with increasing volume fraction gradient exponent, whereas the interface stresses decreased on the prostheses surfaces. A limited increase was also observed at the surfaces of the bone and cement. The periprosthetic femur with a noncemented prosthesis exhibited higher strain energy than with a cemented prosthesis. Radial prostheses implantation displayed more strain energy than longitudinal prostheses implantation in the femoral proximal part. Functionally graded materials also increased strain energy and exhibited promising potentials as substitutes of conventional materials to decrease stress shielding and to enhance total hip replacement lifespan.
Satisfaction and problems experienced with wrist movements: comparison between a common body-powered prosthesis and a new biomechatronics prosthesis

Abd Razak NA, Abu Osman NA, Kamyab M, Wan Abas WA, Gholizadeh H

Am J Phys Med Rehabil, 2014 May;93(5):437-44.
PMID: 24429510 DOI: 10.1097/PHM.0b013e3182a51fc2

This report compares wrist supination and pronation and flexion and extension movements with the common body-powered prosthesis and a new biomechatronics prosthesis with regard to patient satisfaction and problems experienced with the prosthesis. Fifteen subjects with traumatic transradial amputation who used both prosthetic systems participated in this study. Each subject completed two questionnaires to evaluate their satisfaction and problems experienced with the two prosthetic systems. Satisfaction and problems with the prosthetic's wrist movements were analyzed in terms of the following: supination and pronation; flexion and extension; appearance; sweating; wounds; pain; irritation; pistoning; smell; sound; durability; and the abilities to open a door, hold a cup, and pick up or place objects. This study revealed that the respondents were more satisfied with the biomechatronics wrist prosthesis with regard to supination and pronation, flexion and extension, pain, and the ability to open a door. However, satisfaction with the prosthesis showed no significant differences in terms of sweating, wounds, irritation, pistoning, smell, sound, and durability. The abilities to hold a cup and pick up or place an object were significantly better with the body-powered prosthesis. The results of the survey suggest that satisfaction and problems with wrist movements in persons with transradial amputation can be improved with a biomechatronics wrist prosthesis compared with the common body-powered prosthesis.
Fulltext Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7

Yong KW, Li Y, Liu F, Bin Gao, Lu TJ, Wan Abas WA, et al.

Sci Rep, 2016 10 05;6:33067.
PMID: 27703175 DOI: 10.1038/srep33067

Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future.
Fulltext The validity and reliability of motion analysis in patellar tendon reflex assessment

Tham LK, Abu Osman NA, Wan Abas WA, Lim KS

PLoS One, 2013;8(2):e55702.
PMID: 23409022 DOI: 10.1371/journal.pone.0055702

The deep tendon reflex assessments that are essential to the accurate diagnosis of neurological or neuromuscular disorders are conducted subjectively in clinical neurology. Our aim was to assess deep tendon reflexes objectively with a new reflex quantification method.
The effects of hypoxia and serum-free conditions on the stemness properties of human adipose-derived stem cells

Wan Safwani WK, Wong CW, Yong KW, Choi JR, Mat Adenan NA, Omar SZ, et al.

Cytotechnology, 2016 Oct;68(5):1859-72.
PMID: 26728363 DOI: 10.1007/s10616-015-9939-9

The need to have a better and safer culture condition for expansion of human mesenchymal stem cells (MSCs) is crucial particularly to prevent infection and immune rejection. This is normally associated with the use of animal-based serum in the culture media for cell expansion. The aim of this study is to investigate alternative culture conditions which may provide better and safer environment for cell growth. In the present study, human adipose-derived stem cells (ASCs) at passage 3 were subjected to treatment in 4 conditions: (1) 21 % O2 with fetal bovine serum (FBS), (2) 21 % O2 without FBS, (3) 2 % O2 with FBS and (4) 2 % O2 without FBS followed by subsequent analysis of their phenotype, viability and functionality. We observed that ASCs cultured in all conditions present no significant phenotypic changes. It was found that ASCs cultured in 2 % O2 without serum showed an increase in viability and growth to a certain extent when compared to those cultured in 21 % O2 without serum. However, ASCs cultured in 2 % O2 without serum displayed a relatively low adipogenic and osteogenic potential. On the other hand, interestingly, there was a positive enhancement in chondrogenic differentiation of ASCs cultured in 21 % O2 without serum. Our findings suggest that different culture conditions may be suitable for different indications. In summary, ASCs cultured in serum-free condition can still survive, proliferate and undergo subsequent adipogenic, osteogenic and chondrogenic differentiation. Therefore, FBS is feasible to be excluded for culture of ASCs, which avoids clinical complications.
Cryopreservation of Human Mesenchymal Stem Cells for Clinical Applications: Current Methods and Challenges

Yong KW, Wan Safwani WK, Xu F, Wan Abas WA, Choi JR, Pingguan-Murphy B

Biopreserv Biobank, 2015 Aug;13(4):231-9.
PMID: 26280501 DOI: 10.1089/bio.2014.0104

Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications.
Transtibial prosthetic suspension: less pistoning versus easy donning and doffing

Gholizadeh H, Abu Osman NA, Eshraghi A, Ali S, Sævarsson SK, Wan Abas WA, et al.

J Rehabil Res Dev, 2012;49(9):1321-30.
PMID: 23408214

Poor suspension increases slippage of the residual limb inside the socket during ambulation. The main purpose of this article is to evaluate the pistoning at the prosthetic liner-socket interface during gait and assess patients' satisfaction with two different liners. Two prostheses with seal-in and locking liners were fabricated for each of the 10 subjects with transtibial amputation. The Vicon motion system was used to measure the pistoning during gait. The subjects were also asked to complete a Prosthesis Evaluation Questionnaire. The results revealed higher pistoning inside the socket during gait with the locking liner than with the seal-in liner (p < 0.05). The overall satisfaction with the locking liner was higher (p < 0.05) because of the relative ease with which the patients could don and doff the device. As such, pistoning may not be the main factor that determines patients' overall satisfaction with the prosthesis and other factors may also contribute to comfort and satisfaction with prostheses. The article also verifies the feasibility of the Vicon motion system for measuring pistoning during gait.
The effect of Dermo and Seal-In X5 prosthetic liners on pressure distributions and reported satisfaction during ramp ambulation in persons with transtibial limb loss

Ali S, Osman NA, Razak A, Hussain S, Wan Abas WA

Eur J Phys Rehabil Med, 2015 Feb;51(1):31-7.
PMID: 24963603

Lower limb amputee's are greatly affected in dealing with the environmental barriers such as ramps and stairs and reported high interface pressure between the residual limb and socket/liner. Interface pressure between the residual limb and socket/liner can affect the satisfaction and use of the prosthesis. Until now, little attention has been paid to interface pressure between socket and stump during ramp negotiation and its effect on amputee's satisfaction.
Fulltext Review of the socket design and interface pressure measurement for transtibial prosthesis

Pirouzi G, Abu Osman NA, Eshraghi A, Ali S, Gholizadeh H, Wan Abas WA

ScientificWorldJournal, 2014;2014:849073.
PMID: 25197716 DOI: 10.1155/2014/849073

Socket is an important part of every prosthetic limb as an interface between the residual limb and prosthetic components. Biomechanics of socket-residual limb interface, especially the pressure and force distribution, have effect on patient satisfaction and function. This paper aimed to review and evaluate studies conducted in the last decades on the design of socket, in-socket interface pressure measurement, and socket biomechanics. Literature was searched to find related keywords with transtibial amputation, socket-residual limb interface, socket measurement, socket design, modeling, computational modeling, and suspension system. In accordance with the selection criteria, 19 articles were selected for further analysis. It was revealed that pressure and stress have been studied in the last decaeds, but quantitative evaluations remain inapplicable in clinical settings. This study also illustrates prevailing systems, which may facilitate improvements in socket design for improved quality of life for individuals ambulating with transtibial prosthesis. It is hoped that the review will better facilitate the understanding and determine the clinical relevance of quantitative evaluations.
Fulltext Balance and risk of fall in individuals with bilateral mild and moderate knee osteoarthritis

Khalaj N, Abu Osman NA, Mokhtar AH, Mehdikhani M, Wan Abas WA

PLoS One, 2014;9(3):e92270.
PMID: 24642715 DOI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39584

Balance is essential for mobility and performing activities of daily living. People with knee osteoarthritis display impairment in knee joint proprioception. Thus, the aim of this study was to evaluate balance and risk of fall in individuals with bilateral mild and moderate knee osteoarthritis. Sixty subjects aged between 50 and 70 years volunteered in this study. They were categorized into three groups which were healthy (n = 20), mild (n = 20) and moderate (n = 20) bilateral knee osteoarthritis groups. Dynamic and static balance and risk of fall were assessed using Biodex Stability System. In addition, Timed Up and Go test was used as a clinical test for balance. Results of this study illustrated that there were significant differences in balance (dynamic and static) and risk of fall between three groups. In addition, the main (most significant) difference was found to be between healthy group and moderate group. Furthermore, on clinical scoring of balance, the "Timed Up and Go" test, all three groups showed significant difference. In conclusion, bilateral knee osteoarthritis impaired the balance and increased the risk of fall, particularly in people with moderate knee osteoarthritis.
Fulltext Gait biomechanics of individuals with transtibial amputation: effect of suspension system

Eshraghi A, Abu Osman NA, Karimi M, Gholizadeh H, Soodmand E, Wan Abas WA

PLoS One, 2014;9(5):e96988.
PMID: 24865351 DOI: 10.1371/journal.pone.0096988

Prosthetic suspension system is an important component of lower limb prostheses. Suspension efficiency can be best evaluated during one of the vital activities of daily living, i.e. walking. A new magnetic prosthetic suspension system has been developed, but its effects on gait biomechanics have not been studied. This study aimed to explore the effect of suspension type on kinetic and kinematic gait parameters during level walking with the new suspension system as well as two other commonly used systems (the Seal-In and pin/lock). Thirteen persons with transtibial amputation participated in this study. A Vicon motion system (six cameras, two force platforms) was utilized to obtain gait kinetic and kinematic variables, as well as pistoning within the prosthetic socket. The gait deviation index was also calculated based on the kinematic data. The findings indicated significant difference in the pistoning values among the three suspension systems. The Seal-In system resulted in the least pistoning compared with the other two systems. Several kinetic and kinematic variables were also affected by the suspension type. The ground reaction force data showed that lower load was applied to the limb joints with the magnetic suspension system compared with the pin/lock suspension. The gait deviation index showed significant deviation from the normal with all the systems, but the systems did not differ significantly. Main significant effects of the suspension type were seen in the GRF (vertical and fore-aft), knee and ankle angles. The new magnetic suspension system showed comparable effects in the remaining kinetic and kinematic gait parameters to the other studied systems. This study may have implications on the selection of suspension systems for transtibial prostheses. Trial registration: Iranian Registry of Clinical Trials IRCT2013061813706N1.
Fulltext The effects of prosthetic foot type and visual alteration on postural steadiness in below-knee amputees

Arifin N, Abu Osman NA, Ali S, Wan Abas WA

Biomed Eng Online, 2014;13(1):23.
PMID: 24597518 DOI: 10.1186/1475-925X-13-23

Achieving independent upright posture has known to be one of the main goals in rehabilitation following lower limb amputation. The purpose of this study was to compare postural steadiness of below knee amputees with visual alterations while wearing three different prosthetic feet.
Effect of exercise and gait retraining on knee adduction moment in people with knee osteoarthritis

Khalaj N, Abu Osman NA, Mokhtar AH, Mehdikhani M, Wan Abas WA

Proc Inst Mech Eng H, 2014 Feb;228(2):190-9.
PMID: 24458100 DOI: 10.1177/0954411914521155

The knee adduction moment represents the medial knee joint load, and greater value is associated with higher load. In people with knee osteoarthritis, it is important to apply proper treatment with the least side effects to reduce knee adduction moment and, consequently, reduce medial knee joint load. This reduction may slow the progression of knee osteoarthritis. The research team performed a literature search of electronic databases. The search keywords were as follows: knee osteoarthritis, knee adduction moment, exercise program, exercise therapy, gait retraining, gait modification and knee joint loading. In total, 12 studies were selected, according to the selection criteria. Findings from previous studies illustrated that exercise and gait retraining programs could alter knee adduction moment in people with knee osteoarthritis. These treatments are noninvasive and nonpharmacological which so far have no or few side effects, as well as being low cost. The results of this review revealed that gait retraining programs were helpful in reducing the knee adduction moment. In contrast, not all the exercise programs were beneficial in reducing knee adduction moment. Future studies are needed to indicate best clinical exercise and gait retraining programs, which are most effective in reducing knee adduction moment in people with knee osteoarthritis.
Study design: systematic review
Fulltext Evaluation of new suspension system for limb prosthetics

Gholizadeh H, Abu Osman NA, Eshraghi A, Ali S, Arifin N, Wan Abas WA

Biomed Eng Online, 2014;13:1.
PMID: 24410918 DOI: 10.1186/1475-925X-13-1

Good prosthetic suspension system secures the residual limb inside the prosthetic socket and enables easy donning and doffing. This study aimed to introduce, evaluate and compare a newly designed prosthetic suspension system (HOLO) with the current suspension systems (suction, pin/lock and magnetic systems).
Fulltext Influence of age on patellar tendon reflex response

Chandrasekhar A, Abu Osman NA, Tham LK, Lim KS, Wan Abas WA

PLoS One, 2013;8(11):e80799.
PMID: 24260483 DOI: 10.1371/journal.pone.0080799

BACKGROUND: A clinical parameter commonly used to assess the neurological status of an individual is the tendon reflex response. However, the clinical method of evaluation often leads to subjective conclusions that may differ between examiners. Moreover, attempts to quantify the reflex response, especially in older age groups, have produced inconsistent results. This study aims to examine the influence of age on the magnitude of the patellar tendon reflex response.
METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted using the motion analysis technique with the reflex responses measured in terms of knee angles. Forty healthy subjects were selected and categorized into three different age groups. Patellar reflexes were elicited from both the left and right patellar tendons of each subject at three different tapping angles and using the Jendrassik maneuver. The findings suggested that age has a significant effect on the magnitude of the reflex response. An angle of 45° may be the ideal tapping angle at which the reflex can be elicited to detect age-related differences in reflex response. The reflex responses were also not influenced by gender and were observed to be fairly symmetrical.
CONCLUSIONS/SIGNIFICANCE: Neurologically normal individuals will experience an age-dependent decline in patellar reflex response.
Fulltext Balance control in lower extremity amputees during quiet standing: a systematic review

Ku PX, Abu Osman NA, Wan Abas WA

Gait Posture, 2014 Feb;39(2):672-82.
PMID: 24331296 DOI: 10.1016/j.gaitpost.2013.07.006

Postural control has been widely evaluated for the normal population and different groups over the past 20 years. Numerous studies have investigated postural control in quiet standing posture among amputees. However, a comprehensive analysis is lacking on the possible contributing factors to balance. The present systematic review highlights the current findings on variables that contribute to balance instability for lower extremity amputees. The search strategy was performed on PubMed, Web of Science, Medline, Scopus, and CINAHL and then followed by additional manual searching via reference lists in the reviewed articles. The quality of the articles was evaluated using a methodological quality assessment tool. This review included and evaluated a total of 23 full-text articles. Despite the inconsistencies in the methodological design of the studies, all articles scored above the acceptable level in terms of quality. A majority of the studies revealed that lower extremity amputees have increased postural sway in the standing posture. Asymmetry in body weight, which is mainly distributed in the non-amputated leg, was described. Aside from the centre of pressure in postural control, sensory inputs may be a related topic for investigation in view of evidence on their contribution, particularly visual input. Other balance-related factors, such as stump length and patients' confidence level, were also neglected. Further research requires examination on the potential factors that affect postural control as the information of standing postural is still limited.
Fulltext Interface pressure in transtibial socket during ascent and descent on stairs and its effect on patient satisfaction

Ali S, Abu Osman NA, Eshraghi A, Gholizadeh H, Abd Razak NA, Wan Abas WA

Clin Biomech (Bristol, Avon), 2013 Nov-Dec;28(9-10):994-9.
PMID: 24161521 DOI: 10.1016/j.clinbiomech.2013.09.004

Transtibial amputees encounter stairs and steps during their daily activities. The excessive pressure between residual limb/socket may reduce the walking capability of transtibial prosthetic users during ascent and descent on stairs. The purposes of the research were to evaluate the interface pressure between Dermo (shuttle lock) and Seal-In X5 (prosthetic valve) interface systems during stair ascent and descent, and to determine their satisfaction effects on users.

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