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.

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.

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.

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.

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.

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.

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.

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.

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.

Laser surface modification of poly(epsilon-caprolactone) (PCL) membrane for tissue engineering applications.

Ultra-thin polycaprolactone (PCL) produced by bi-axial stretching was previously shown to have significant advantage for membrane tissue engineering. However, the permeability of the membrane needs to be enhanced. In this study, ablation experiments using femtosecond laser and excimer laser were carried out to modify the PCL surface. The use of the femtosecond laser produces neat drilled-through holes while the excimer laser is employed to produce blind-holes on the membrane. The modified surface of the membrane was studied and analyzed for different laser parameters (such as pulse energy and pulse repetition rate and characterized using several techniques that include optical microscopy, scanning electron microscopy and water contact angle measurements). Results showed that the morphological surface changes with different laser parameters, and the water contact angle decreases as the surface of the membrane is modified. The decrease in water contact angle suggests that surface of the membrane had become more hydrophilic than the non-laser treated membrane. The present study demonstrated that laser surface modification on the PCL can be achieved with high degree of success and precision. This paved the way for further enhancement in membrane tissue engineering.

Novel PCL-based honeycomb scaffolds as drug delivery systems for rhBMP-2.

This study investigated a novel drug delivery system (DDS), consisting of polycaprolactone (PCL) or polycaprolactone 20% tricalcium phosphate (PCL-TCP) biodegradable scaffolds, fibrin Tisseel sealant and recombinant bone morphogenetic protein-2 (rhBMP-2) for bone regeneration. PCL and PCL-TCP-fibrin composites displayed a loading efficiency of 70% and 43%, respectively. Fluorescence and scanning electron microscopy revealed sparse clumps of rhBMP-2 particles, non-uniformly distributed on the rods' surface of PCL-fibrin composites. In contrast, individual rhBMP-2 particles were evident and uniformly distributed on the rods' surface of the PCL-TCP-fibrin composites. PCL-fibrin composites loaded with 10 and 20 microg/ml rhBMP-2 demonstrated a triphasic release profile as quantified by an enzyme-linked immunosorbent assay (ELISA). This consisted of burst releases at 2 h, and days 7 and 16. A biphasic release profile was observed for PCL-TCP-fibrin composites loaded with 10 microg/ml rhBMP-2, consisting of burst releases at 2 h and day 14. PCL-TCP-fibrin composites loaded with 20 microg/ml rhBMP-2 showed a tri-phasic release profile, consisting of burst releases at 2 h, and days 10 and 21. We conclude that the addition of TCP caused a delay in rhBMP-2 release. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and alkaline phosphatase assay verified the stability and bioactivity of eluted rhBMP-2 at all time points.

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.

Computational biomechanical modelling of the lumbar spine using marching-cubes surface smoothened finite element voxel meshing.

There is a need for the development of finite element (FE) models based on medical datasets, such as magnetic resonance imaging and computerized tomography in computation biomechanics. Direct conversion of graphic voxels to FE elements is a commonly used method for the generation of FE models. However, conventional voxel-based methods tend to produce models with jagged surfaces. This is a consequence of the inherent characteristics of voxel elements; such a model is unable to capture the geometries of anatomical structures satisfactorily. We have developed a robust technique for the automatic generation of voxel-based patient-specific FE models. Our approach features a novel tetrahedronization scheme that incorporates marching-cubes surface smoothing together with a smooth-distortion factor (SDF). The models conform to the actual geometries of anatomical structures of a lumbar spine segment (L3). The resultant finite element analysis (FEA) at the surfaces is more accurate compared to the use of conventional voxel-based generated FE models. In general, models produced by our method were superior compared to that obtained using the commercial software ScanFE.

Effect of saline solution on creep fracture of Delrin.

Delrin as an implant material has been widely used for more than 26 yr. To determine the combined effect of stress and body fluid environment on the stress limits of polyacetal, the creep rupture behaviour of Delrin in saline (0.9% NaCl) solution at 37 degrees C was studied. A creep rupture model was used to predict the upper (immediate fracture) and lower (no fracture) stress limits and the elastic ratio (Ee/Ea). The results showed that saline solution adversely affected the lower stress limit and Ee/Ea, but not the upper stress limit. Brittle fracture with a strain < 5% occurred for most specimens. This may explain why Delrin can fail prematurely in orthopaedic implants. Design stresses using Delrin as implant material have to be reduced by four times to 5 MPa and the strain limited to 5% as opposed to 20%, as previously believed. The increase in Ee/Ea also implied that the microdeformation mechanism is changed. The presence of surface cracks indicated that Delrin is susceptible to environmental stress cracking in saline solution.

Cold extrusion deformation of UHMWPE in total knee replacement prostheses.

The use of metal-backed tibial plates in total knee replacement prostheses can result in the flow of ultra-high molecular weight polyethylene (UHMWPE) from the tibial insert into a cavity on the metal tray surface. A study of the relationship between the thickness of UHMWPE inserts and the amount of cold extrusion is reported here. An attempt was made to correlate the occurrence of cold extrusion with computer-aided analysis. UHMWPE samples of varying thickness, from 3 mm to 10 mm, were placed over cobalt-chrome (Co-Cr) discs. The Co-Cr discs had a 5 mm diameter hole placed centrally to simulate a tibial tray cavity. A cyclic load was applied at 20 Hz through a Co-Cr spherical indentor for a million cycles. The application of cyclic loading on UHMWPE samples resulted in cold-extrusion values comparable to those reported for retrieval analysis studies. Results after fatigue loading show that the samples do not suffer any gross surface damage. A shiny depression was visible at the load application site and the surface roughness value was decreased. The amount of cold extrusion increased with decreasing UHMWPE sample thickness. From the results, a minimum UHMWPE thickness of 12 mm is required if cold extrusion of UHMWPE is to be eliminated.

Effect of pore sizes and cholesterol-lipid solution on the fracture toughness of pure titanium sintered compacts.

Commercial pure titanium has been widely used as an implant material because of its excellent biocompatibility and good ductility. To determine the effect of pore size on the fracture resistance of porous titanium compacts, a series of fracture toughness (KQ) tests were performed on commercial pure titanium powder compacted to 0.17 and 0.62 GPa. Pore sizes ranged from 25 to 103 microns, with porosity between 8.5 and 35%. Two sets of fracture toughness tests using disc-shaped compacts (ASTM E 399-90) were performed, the first in air at 37 degrees C and the second with compacts treated in cholesterol-lipid solution at 37 degrees C. The KQ value of compacts with a smaller mean pore size (ca. 50 microns) was approximately twice that of the compacts with a larger mean pore size (100 microns). The effect of cholesterol-lipid solution treatment was detrimental, perhaps due to preferential lipid absorption by the titanium oxide and/or the presence of chlorides. For the smaller pore size compacts, the KQ values decreased by up to 20%. For the larger pore size compacts, the effect of cholesterol-lipid solution was less significant. Morphologically, compacts with smaller pore size had a predominantly ductile fracture with significantly higher dimple density than the larger pore size compacts.

Hybrid biomaterials based on the interaction of polyurethane oligomers with porcine pericardium.

Hybrid biomaterials have been produced by the interaction of polyurethane oligomers with both fresh and glutaraldehyde-fixed porcine pericardium. The hybrid biomaterials so formed were translucent with occasional white streaks and/or spots, had increased stiffness (to touch) but remained pliable. No shrinkage temperature was detected for fresh porcine pericardium hybrid up to 100 degrees C compared to porcine pericardium (approximately 67 degrees C) and glutaraldehyde-fixed porcine pericardium (approximately 87 degrees C). Amino acid analysis of the fresh porcine pericardium hybrid showed a reduction in lysine content after active isocyanate-terminated polyurethane oligomers exposure, indicating cross-linking between the polymer and tissue. Histological examination of the hybrid material shows a thin grey coating on both surfaces of the tissue, implying at least surface cross-linking of the tissue with polyurethane. The results suggest that fresh porcine pericardium can be reacted with active isocyanate-terminated polyurethane oligomers to produce hybrid biomaterials with covalent bonding.