Autologous bone marrow clot as an alternative to autograft for bone defect healing.

OBJECTIVES: Long bone defects often require surgical intervention for functional restoration. The 'gold standard' treatment is autologous bone graft (ABG), usually from the patient's iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done. METHODS: We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses. RESULTS: Comparable results were obtained with autologous BMA clot and ABG, except for the quantification of new bone by micro-CT. Significantly more bone was found in the ABG-treated ulnar defects than in those treated with autologous BMA clot. This is possibly due to the remnants of necrotic autograft fragments that persisted within the healing defects at week 12 post-surgery. CONCLUSION: As similar treatment outcomes were achieved by the two strategies, the preferred treatment would be one that is associated with a lower risk of complications. Hence, these results demonstrate that coagulated BMA can be considered as an alternative autogenous therapy for long bone healing.Cite this article: Z. X. H. Lim, B. Rai, T. C. Tan, A. K. Ramruttun, J. H. Hui, V. Nurcombe, S. H. Teoh, S. M. Cool. Autologous bone marrow clot as an alternative to autograft for bone defect healing. Bone Joint Res 2019;8:107-117. DOI: 10.1302/2046-3758.83.BJR-2018-0096.R1.

pSTAT3 and MYC in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

INTRODUCTION: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin's lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway. MATERIALS AND METHODS: 51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement. RESULTS: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression. CONCLUSION: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.

A global meta-analysis of the economic values of provisioning and cultural ecosystem services.

Despite a growing demand to integrate ecosystem services into sustainability decision-making, our understanding of the global distribution of the economic value of ES is scarce. We extracted information from provisioning and cultural ecosystem services (PCES) from The Economics of Ecosystems and Biodiversity (TEEB) database using a meta-analytical approach. We then employed geostatistical methods to analyze the relationship between economic values and environmental and socio-economic predictors. Here we show that anthropogenic related factors such as accessibility, spatially explicit gross domestic product and ecosystem services scarcity explain global trends of PCES economic values. We observe higher PCES values in agricultural areas of strong human presence such as the British Isles, Southwest of Brazil and India and lower values in less disturbed natural areas. These findings highlight the decisive role that human systems play in the economic realization of PCES and caution that single-criterion sustainability and conservation policies aimed at maximizing the economic returns of PCES may not overlap with wild nature.

Patients' blood pressure control and doctors' adherence to hypertension clinical practice guideline in managing patients at health clinics in Kuala Muda district, Kedah.

BACKGROUND: blood pressure (bP) control among Malaysian is poor and doctor's adherence to clinical practice guideline (cPG) has been a well-known factor that may improve it. this study was designed to evaluate patients' bP control, doctors' adherence to the latest hypertension cPG and their association. Factors associated with bP control and cPG adherence was also examined. METHODS: A cross-sectional study was conducted in Kuala Muda district's health clinics. 331 medical records were selected using stratified random sampling and standard proforma was used for data collection. the latest edition of the Malaysian cPG on hypertension was employed to define related variables. RESULTS: A total of 160 patients (48.3%) had controlled bP and it was significantly associated with patients' age (adjusted Odds ratio, aOr= 1.03, 95% cI: 1.004, 1.05, p= 0.016) and systolic bP at presentation (aOr= 0.95, 95% cI: 0.93, 0.96, p< 0.001). About 60.7% of the medical records showed doctor's good level of cPG adherence. this adherence has significant association with presence of chronic kidney disease (aOr= 0.51, 95% cI: 0.31, 0.85, p= 0.007) and cardiovascular disease (aOr= 2.68, 95% cI: 1.04, 6.95, p= 0.030) in the patients and physicians' treatment intensification (aOr= 2.00, 95% cI: 1.26, 3.19, p= 0.009). However, no association was found between bP control and cPG adherence. CONCLUSION: Hypertension control in this study was poor and the prevalence of physicians with good level of cPG adherence was slightly above average. these findings are important for relevant stakeholders to strategise an action plan to improve hypertension management outcome.

Angry patient with fibromyalgia: Diagnosis and management in primary care.

I report a case of 40-year-old lady who presented with symptoms and signs suggestive of fibromyalgia but was disregarded by attending doctor. She was infuriated and lodged a complaint to Family Medicine Specialist (FMS) whereby further assessment confirmed the diagnosis of fibromyalgia and subsequently treated in primary care setting.

Subablative Er:YAG laser effect on enamel demineralization.

OBJECTIVES: To characterize the cariostatic potential of a low-energy Er:YAG laser treatment. METHODS: Twelve sound premolars were selected. Two 2 × 1 mm windows were created on each tooth and randomly assigned to L(1) and L(2) groups. Three sites in each window were chosen with the middle site as the control and the left and right ones receiving Er:YAG laser treatment of 5.1 J/cm(2) (L(1)) or 2.0 J/cm(2) (L(2)), respectively. The teeth were further subjected to 4-day pH cycling to create caries-like lesions. After mineral quantification using a micro-computed tomography scanner, the preventive effects (ΔML = mineral loss of the control area minus that of the lased area) of L(1) and L(2) treatments were calculated based on the difference in the gray value of the control and lased sites. RESULTS: Significant inhibitory effects of L(1) and L(2) on enamel demineralization were demonstrated (both p ≤ 0.001), with the L(1) treatment having a greater effect (45.2%) than the L(2) treatment (25.2%, p = 0.004). CONCLUSIONS: Subablative low-energy Er:YAG laser irradiation can significantly prevent enamel demineralization potentially through the retardation of enamel diffusion. This study confirmed that high-energy laser treatment, which may damage the peripheral and underlying tissues, may not be needed for caries prevention.

Potential mechanism for the laser-fluoride effect on enamel demineralization.

Laser-induced prevention of dental caries has been studied extensively. However, the cariostatic mechanisms of a combined fluoride-laser treatment are not well-understood. Using micro- computed tomography (micro-CT), we quantified the effect of fluoride and/or Er:YAG laser treatment on enamel demineralization. The mean mineral loss (%/V) for each group was 4,870 ± 1,434 (fluoride followed by laser treatment), 6,341 ± 2,204 (laser treatment), 7,669 ± 2,255 (fluoride treatment), and 10,779 ± 2,936 (control). The preventive effect of the laser (p < 0.001) and fluoride (p = 0.010) treatment was statistically significant. Characterized by micro-x-ray diffraction (XRD) analysis, the significant contraction in the a-axis after both laser and combined laser/fluoride treatment was revealed (both p < 0.05). In conclusion, subablative low-energy Er:YAG laser irradiation following fluoride treatment may instantaneously transform enamel hydroxyapatite into fluoridated hydroxyapatite to reduce enamel solubility as a preventive treatment for enamel demineralization.

A multiscale model for bioimpedance dispersion of liver tissue.

Radio-frequency ablation (RFA) has been used in liver surgery to minimize blood loss during tissue division. However, the current RFA tissue division method lacks an effective way of determining the stoppage of blood flow. There is limitation on the current state-of-the-art laser Doppler flow sensor due to its small sensing area. A new technique was proposed to use bioimpedance for blood flow sensing. This paper discusses a new geometrical multiscale model of the liver bioimpedance incorporating blood flow impedance. This model establishes correlation between the physical tissue structure and bioimpedance measurement. The basic Debye structure within a multilevel framework is used in the model to account for bioimpedance dispersion. This dispersion is often explained by the Cole-Cole model that includes a constant phase element without physical explanation. Our model is able to account for reduced blood flow in its output with changes in permittivity in gamma dispersion that is mainly due to the polarization of water molecules. This study demonstrates the potential of a multiscale model in determining the stoppage of blood flow during surgery.

Lateral ridge augmentation using a PCL-TCP scaffold in a clinically relevant but challenging micropig model.

BACKGROUND: In implant dentistry, there is a need for synthetic bone substitute blocks to support ridge augmentation in situations where large bone volumes are missing. Polycaprolactone-based scaffolds demonstrated excellent results in bone tissue engineering applications. The use of customized polycaprolactone-tricalcium phosphate (PCL-TCP) displayed promising results from recent rat femur and rabbit calvaria studies. However, data from clinically representative models in larger animals do not exist. OBJECTIVE: To evaluate new bone formation in association with a novel PCL-TCP scaffold in comparison with an autogenous bone block graft for the reconstruction of large dentoalveolar defects in a clinically relevant but challenging pig jaw model. MATERIAL AND METHODS: Chronic, non-contained one-wall defects were created in the mandible of micropigs and randomly assigned to receive one of the following guided bone regeneration (GBR) procedures for a period of 6 months. (A) Collagen membrane + autogenous block graft or (B) Collagen membrane + PCL-TCP scaffold. Micro computed tomography (µ-CT), histology and histomorphometry were used to assess new bone formation. RESULTS: Although µ-CT and histomorphometric analysis demonstrated a slight discrepancy between the measurements, the group utilizing autogenous bone grafts consistently reported superior new bone formation as compared to PCL-TCP scaffolds. When measured using µ-CT, the ratio of bone volume fraction for PCL-TCP scaffolds with respect to autografts yielded a mean efficacy of approximately 51%. Histological examination revealed that under favorable conditions, the new bone matrix and new bone marrow were in direct contact with the PCL-TCP scaffold rods and invading the interstices, suggesting good biocompatibility and high osteoconductivity. Autograft block grafts demonstrated 48.5-57.4% of pronounced resorption after 6 months following ridge augmentation. CONCLUSIONS: PCL-TCP scaffolds have demonstrated the potential application for lateral ridge augmentation following a healing period of 6 months in a micropig model.

High tibial osteotomy using polycaprolactone-tricalcium phosphate polymer wedge in a micro pig model.

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.

Design of a mechanical larynx with agarose as a soft tissue substitute for vocal fold applications.

Mechanical and computational models consisting of flow channels with convergent and oscillating constrictions have been applied to study the dynamics of human vocal fold vibration. To the best of our knowledge, no mechanical model has been studied using a material substitute with similar physical properties to the human vocal fold for surgical experimentation. In this study, we design and develop a mechanical larynx with agarose as a vocal fold substitute, and assess its suitability for surgical experimentation. Agarose is selected as a substitute for the vocal fold as it exhibits similar nonlinear hyperelastic characteristics to biological soft tissue. Through uniaxial compression and extension tests, we determined that agarose of 0.375% concentration most closely resembles the vocal fold mucosa and ligament of a 20-year old male for small tensile strain with an R(2) value of 0.9634 and root mean square error of 344.05±39.84 Pa. Incisions of 10 mm lengthwise and 3 mm in depth were created parallel to the medial edge on the superior surface of agar phantom. These were subjected to vibrations of 80, 130, and 180 Hz, at constant amplitude of 0.9 mm over a period of 10 min each in the mechanical larynx model. Lateral expansion of the incision was observed to be most significant for the lower frequency of 80 Hz. This model serves as a basis for future assessments of wound closure techniques during microsurgery to the vocal fold.

Surface modification of PCL-TCP scaffolds improve interfacial mechanical interlock and enhance early bone formation: an in vitro and in vivo characterization.

Pretreatment of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds under alkaline conditions can be utilized to alter surface characteristics for enhanced early bone formation. PCL-TCP scaffolds were treated with sodium hydroxide (NaOH) at various time intervals (group A: untreated, group B: 3M NaOH for 48 h, and group C: 3M NaOH for 96 h). In vitro results showed a greater degree of physical changes in the NaOH-treated scaffolds (B and C) than the untreated group (A). Clearly, the NaOH-treated scaffolds showed an increased surface roughness than the untreated ones. A significantly large number of "channel-like" pits and greater average pit sizes were detected in groups B (14.51 +/- 10.9 microm) and C (20.27 +/- 14.3 microm); and absent in group A. In addition, treated scaffolds had a significant reduction of the water contact angle (40.9-58.2%). Favorably, the pore dimensions and scaffold rod thickness remained unchanged throughout the experiment. When implanted in the calvaria of rabbits, NaOH-treated scaffolds reported greater early matrix deposition and bone formation from scanning electron images and Micro-computed tomography analyses. In conclusion, pretreatment of PCL-TCP scaffolds with NaOH increases the wettability and surface area for initial matrix deposition and early bone ingrowth.

Development of dual-compartment perfusion bioreactor for serial coculture of hepatocytes and stellate cells in poly(lactic-co-glycolic acid)-collagen scaffolds.

An important challenge in liver tissue engineering is to overcome the rapid loss of hepatocyte functions. In vivo, hepatocytes are compact polyhedral cells with round nuclei; however, they readily loss many of their differentiated functions in vitro. To overcome this challenge, we have established a new perfusion bioreactor that consists of two compartments which enabled the serial coculture of hepatocytes and hepatic stellate cells-T6 without direct contact between each other. Three dimensional scaffolds were utilized in the bioreactor as physical anchors for cells. The scaffolds consist of collagen grafted poly(lactic-co-glycolic acid) microfibers and cross-linked collagen sponges between microfibers for additional cellular support and adhesion. The advantages of this new bioreactor are enabling cell culture in three dimensional organization and controlling the culture parameters of the supporting cells independently from the hepatocytes. The results showed that the hepatocytes exhibited much higher levels of the differentiated functions such as albumin secretion, urea synthesis, and cytochrome P450 enzymatic activity when compared with the monoculture system where hepatocytes alone were cultured. This perfusion bioreactor system has potential applications in the development of bioartificial liver devices or cell-based tissue constructs transplantation therapies.

A biomechanical model for real-time simulation of PMMA injection with haptics.

We have developed a computationally efficient rheological model to simulate polymethylmethacrylate (PMMA) injection into cancellous bone during percutaneous vertebroplasty. The model employs the Hagen-Poiseuille law to predict pressure drop across a delivery cannula with viscoelastic changes of curing PMMA modeled via a time and shear-rate-dependent power law. The power law was derived based on dynamic rheological testing of curing PMMA samples. In conjunction with a branching-pipe geometrical model that is reconstructed from micro-computed tomography scans of cancellous bone for estimating pressure changes during PMMA flow in bone, the method provides a fast estimation of overall injection pressure, and, hence, the reaction force during manual PMMA injection.

Bone material properties and fracture analysis: needle insertion for spinal surgery.

The effectiveness of percutaneous needle-based therapy and biopsy is demonstrated in a wide variety of medical problems including spinal disorders. Combined with osteoporosis, spinal disorders are increasingly prevalent as our society ages. However, the final position of the needle depends on a complex interplay of material properties of the bone and/or pathology, as well as the shape and material of the needle, and the insertion dynamics. This paper is a survey of the literature in the area of bone material properties and needle/bone interaction in the context of needle placement. It describes research findings on bone material properties and fractures using micro-CT imaging, and integrative imaging. This review paper also discusses the feasibility of using computational methods to predict fracture by simulating needle placement on any patient-specific model with both geometrical and mechanical properties approximating those of the patient's anatomy.

The degradation profile of novel, bioresorbable PCL-TCP scaffolds: an in vitro and in vivo study.

Degradation studies of scaffolds are important in bone tissue engineering. Previously, novel poly(epsilon-caprolactone)-20% tricalcium phosphate (PCL-TCP) based scaffolds were developed and proven useful for bone regeneration. In this study in vitro degradation analyses were carried out with the PCL-TCP scaffolds immersed in standard culture medium for 24 weeks. In vivo degradation was performed with the scaffolds implanted in the abdomen of rats for the same period of time. Results demonstrated greater degradation of PCL-TCP scaffolds in vivo than in vitro. At 24 weeks, the increase of average porosity of the scaffolds in vivo was 29.2% compared to 2.65% in vitro. Gel permeation chromatography (GPC) analysis revealed a decrease of 29% and 20% respectively in the Mn and Mw values after 24 weeks in vitro. However, a significant decrease in Mn and Mw values (79.6% and 88.7% respectively) were recorded in vivo. The mechanical properties however, were relatively similar and closely match those of cancellous bone even at 24 weeks. The results showed that the scaffold can be used for dentoalveolar reconstruction and PCL-TCP scaffolds have shown to possess the potential to degrade within the desired time period of 5-6 months and favorable mechanical properties.

Heterogeneous meshing and biomechanical modeling of human spine.

We aim to develop a patient-specific biomechanical model of human spine for the purpose of surgical training and planning. In this paper, we describe the development of a finite-element model of the spine from the VHD Male Data. The finite-element spine model comprises volumetric elements suitable for deformation and other finite-element analysis using ABAQUS. The mesh generation solution accepts segmented radiological slices as input, and outputs three-dimensional (3D) volumetric finite element meshes that are ABAQUS compliant. The proposed mesh generation method first uses a grid plane to divide the contours of the anatomical boundaries and its inclusions into discrete meshes. A grid frame is then built to connect the grid planes between any two adjacent planes using a novel scheme. The meshes produced consist of brick elements in the interior of the contours and with tetrahedral and wedge elements at the boundaries. The nodal points are classified according to their materials and hence, elements can be assigned different properties. The resultant spine model comprises a detailed model of the 7 cervical vertebrae, 12 thoracic vertebrae, 5 lumbar vertebrae, and S1. Each of the vertebrae and intervertebral disc has between 1200 and 6000 elements, and approximately 1200 elements, respectively. The accuracy of the resultant VHD finite element spine model was good based on visual comparison of volume-rendered images of the original CT data, and has been used in a computational analysis involving needle insertion and static deformation. We also compared the mesh generated using our method against two automatically generated models; one consists of purely tetrahedral elements and the other hexahedral elements.

Radio-translucent 3-axis mechanical testing rig for the spine in micro-CT.

To date, no apparatus has yet been devised which would allow the study of bone microstructure of the whole vertebrae under mechanical loading. This paper outlines the design and development of a 3-axis radio-translucent mechanical testing rig for spinal research and testing. This rig is to be used in conjunction with a Shimadzu micro-CT scanner. Several tests were conducted to verify the feasibility of the rig design. First, the maximum range of deformation in compression, flexion\extension, and lateral bending that could be exerted on a goat lumbar functional spinal unit was evaluated using the noncontact digital markers method. Stepwise compression loading was also conducted on a single porcine vertebra and the loading data was compared to results obtained from an industrial grade compression testing machine. Finally, micro-CT scans of a porcine vertebra prior to and at a compression failure strain were obtained. The rig was confirmed to be able to exert pure moment loading in the above mentioned modes of deformation and the extent of deformation was comparable to previous documented results. The stepwise compression loading conducted in the rig was also found to effectively approximate a continuous loading of the same specimen in an industrial grade compression testing machine. Finally, resultant micro-CT images of isotropic resolution 32.80 mum of a porcine vertebra loaded in the rig were obtained. For the first time, trabecular microarchitecture detail of a whole vertebra buckling under 12.1% failure compression strain loading was studied using voxel-data visualization software. These initial series of tests verify the feasibility of the rig as an apparatus incorporating spinal testing and imaging.

An in vitro evaluation of PCL-TCP composites as delivery systems for platelet-rich plasma.

In this study, we first investigated the in vitro degradation properties of biodegradable, bioresorbable polycaprolactone-20% tricalcium phosphate (PCL-TCP) composites immersed in simulated body fluid (SBF) and phosphate buffered saline (PBS). Then, the release profiles of the growth factors present in platelet-rich plasma (PRP) loaded onto the composites incubated in SBF and PBS were compared. Composites immersed in both buffers showed water uptake of 13.7%+/-0.75 at day 1, followed by a constant uptake of 12.1%+/-0.3 until day 12. Henceforth the water uptake declined for SBF- and increased for PBS-soaked composites. The weight loss data did not reveal any trend. SBF- and PBS-soaked samples displayed 1-2% weight loss for 2 and 5 of the ten time points measured respectively. The original protein retention (PR) of the composites was 49.1%+/-1.50. After immersion in SBF and PBS for 4 weeks, the PR was augmented to 88.5%+/-1.40 and 69.1%+/-1.40 correspondingly. PRP after activation contained 164.7+/-24.8, 194+/-43 and 18.3+/-4.75 ng/ml of TGF-beta1, PDGF-BB and IGF-1. Microscopic analysis verified the attachment of PRP to the rods and pores of the composites. Interestingly, the buffers played an important role in determining the release profiles of TGF and PDGF. Firstly, PBS-soaked composites manifested a tri-phasic burst-like profile that was absent in SBF. Secondly, SBF-soaked composites experienced delayed release of the growth factors and total release was not achieved (64.4% for TGF and 60.5% for PDGF), whereas total release was realized for PBS-soaked composites. Lastly, release profiles from SBF-soaked composites were growth factor mediated in terms of their amounts and sizes. This was not observed for PBS-soaked composites. IGF-1, on the other hand, exhibited a progressive reduction in levels over the entire experimental period for both buffers. The mechanisms of release were theorized to be a combination of diffusion, degradation and bioactivity. Since SBF is analogous to our body fluids in terms of its ionic constituents, we expect the elution profiles derived from SBF-soaked samples to more accurately emulate the in vivo situation. In conclusion, this study has deemed PCL-TCP composites as suitable delivery systems for platelet-rich plasma.

Flow modelling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation.

The problem of donor scarcity has led to the recent development of tissue engineering technologies, which aim to create implantable tissue equivalents for clinical transplantation. These replacement tissues are being realised through the use of biodegradable polymer scaffolds; temporary/permanent substrates, which facilitate cell attachment, proliferation, retention and differentiated tissue function. To optimise gas transfer and nutrient delivery, as well as to mimic the fluid dynamic environment present within the body, a dynamic system might be chosen. Experiments have shown that dynamic systems enhance tissue growth, with the aid of scaffolds, as compared to static culture systems. Very often, tissue growth within scaffolds is only seen to occur at the periphery. The present study utilises the Computational Fluid Dynamics package FLUENT, to provide a better understanding of the flow phenomena in scaffolds, within our novel bioreactor system. The uni-axial and bi-axial rotational schemes are studied and compared, based on a vessel rotating speed of 35 rpm. The wall shear stresses within and without the constructs are also studied. Findings show that bi-axial rotation of the vessel results in manifold increases of fluid velocity within the constructs, relative to uni-axial rotation about the X- and Z-axes, respectively.