Biology subjects

Bezuidenhout, D.

Publications and source records attributed to Bezuidenhout, D..

4 recordsLinked to original sources

bioRxiv2020

Micromechanical homogenisation of a hydrogel-filled electrospun scaffold for tissue-engineered epicardial patching of the infarcted heart

This study aimed at developing a formulation to link microscopic structure and macroscopic mechanics of a fibrous scaffold filled with a hydrogel for use as a tissue-engineered patch for local epicardial support of the infarcted heart. Mori-Tanaka mean field homogenisation, closed-cell foam mechanics and finite element (FE) methods were used to represent the macroscopic elastic modulus of the filled fibrous scaffold. The homogenised constitutive description of the scaffold was implemented for an epicardial patch in a FE model of a human cardiac left ventricle (LV) to assess effects of patching on myocardial mechanics and ventricular function in presences of an infarct. The macroscopic elastic modulus of the scaffold was predicted to be 0.287 MPa with the FE method and 0.290 MPa with the closed-cell model for the realistic fibre structure of the scaffold, and 0.108 and 0.540 MPa with mean field homogenization for randomly oriented and completely aligned fibres. Epicardial patching was predicted to reduce maximum myocardial stress in the infarcted LV from 19 kPa (no patch) to 9.5 kPa (patch), and to increase the ventricular ejection fraction from 40% (no patch) to 43% (patch). The predictions of the macroscopic elastic modulus of the realistic scaffold with the FE and the closed-cell model agreed well, and were bound by the mean field homogenisation prediction for random and fully aligned fibre orientation of the scaffold. This study demonstrates the feasibility of homogenization techniques to represent complex multiscale structural features in an simplified but meaningful manner.

bioengineering↗

bioRxiv2019

Electrospun polyester-urethane scaffold preserves mechanical properties and exhibits strain stiffening during in situ tissue ingrowth and degradation

Consistent mechanical performance from implantation through healing and scaffold degradation is highly desired for tissue-regenerative scaffolds, e.g. when used for vascular grafts. The aim of this study was the paired in vivo mechanical assessment of biostable and fast degrading electrospun polyester-urethane scaffolds to isolate the effects of material degradation and tissue formation after implantation. Biostable and degradable polyester-urethane scaffolds with substantial fibre alignment were manufactured by electrospinning. Scaffold samples were implanted paired in subcutaneous position in rats for 7, 14 and 28 days. Morphology, mechanical properties and tissue ingrowth of the scaffolds were assessed before implantation and after retrieval. Tissue ingrowth after 28 days was 83 {+/-} 10% in the biostable scaffold and 77 {+/-} 4% in the degradable scaffold. For the biostable scaffold, the elastic modulus at 12% strain increased significantly between 7 and 14 days and decreased significantly thereafter in fibre but not in cross-fibre direction. The degradable scaffold exhibited a significant increase in the elastic modulus at 12% strain from 7 to 14 days after which it did not decrease but remained at the same magnitude, both in fibre and in cross-fibre direction. Considering that the degradable scaffold loses its material strength predominantly during the first 14 days of hydrolytic degradation (as observed in our previous in vitro study), the consistency of the elastic modulus of the degradable scaffold after 14 days is an indication that the regenerated tissue construct retains it mechanical properties.

bioengineering↗

bioRxiv2019

Tissue ingrowth markedly reduces mechanical anisotropy and stiffness in fibre direction of highly aligned electrospun polyurethane scaffolds

PurposeThe lack of long-term patency of synthetic vascular grafts currently available on the market has directed research towards improving the performance of small diameter grafts. Improved radial compliance matching and tissue ingrowth into the graft scaffold are amongst the main goals for an ideal vascular graft. MethodsBiostable polyurethane scaffolds were manufactured by electrospinning and implanted in subcutaneous and circulatory positions in the rat for 7, 14 and 28 days. Scaffold morphology, tissue ingrowth, and mechanical properties of the scaffolds were assessed before implantation and after retrieval. ResultsTissue ingrowth after 24 days was 96.5 {+/-} 2.3% in the subcutaneous implants and 77.8 {+/-} 5.4% in the circulatory implants. Over the 24 days implantation, the elastic modulus at 12% strain decreased by 59% in direction of the fibre alignment whereas it increased by 1379% transverse to the fibre alignment of the highly aligned scaffold of the subcutaneous implants. The lesser aligned scaffold of the circulatory graft implants exhibited an increase of the elastic modulus at 12% strain by 77% in circumferential direction. ConclusionBased on the observations, it is proposed that the mechanism underlying the softening of the highly aligned scaffold in the predominant fibre direction is associated with scaffold compaction and local displacement of fibres by the newly formed tissue. The stiffening of the scaffold, observed transverse to highly aligned fibres and for more a random fibre distribution, represents the actual mechanical contribution of the tissue that developed in the scaffold.

bioengineering↗

bioRxiv2019

Comparative palatability of orally disintegrating tablets (ODTs) of Praziquantel (L-PZQ and Rac-PZQ) versus current PZQ tablet in African children: a randomized, single-blind, crossover study

BackgroundPraziquantel (PZQ) is currently the only recommended drug for infection and disease caused by the species of schistosome infecting humans; however, the current tablet formulation is not suitable for preschool age children mainly due to its bitterness and the size of the tablet. We assessed the palatability of two new orally disintegrating tablet (ODT) formulations of PZQ.\n\nMethodsThis randomized, single-blind, crossover, swill-and-spit palatability study (NCT02315352) was carried out at a single school in Tanzania in children aged 6-11 years old, irrespective of schistosomiasis infection. Children were stratified according to age group (6-8 years or 9-11 years) and gender, then randomized to receive each formulation in a pre-specified sequence. Over 2 days, the children assessed the palatability of levo-Praziquantel (L-PZQ) ODT 150 mg and Racemate Praziquantel (Rac-PZQ) ODT 150 mg disintegrated in the mouth without water on the first day, and L-PZQ and Rac-PZQ dispersed in water and the currently available PZQ 600 mg formulation (PZQ-Cesol(R)) crushed and dispersed in water on the second day. The palatability of each formulation was rated using a 100 mm visual analogue scale (VAS) incorporating a 5-point hedonic scale, immediately after spitting out the test product (VASt=0 primary outcome) and after 2-5 minutes (VASt=2-5).\n\nFindingsIn total, 48 children took part in the assessment. Overall, there was no reported difference in the VASt=0 between the two ODT formulations (p=0.106) without water. Higher VASt=0 and VASt=2-5 scores were reported for L-PZQ ODT compared with Rac-PZQ ODT in older children (p=0.046 and p=0.026, respectively). The VASt=0 and VASt=2-5 were higher for both ODT formulations compared with the current formulation (p<0.001 for both time points). No serious adverse events were reported.\n\nInterpretationThe new paediatric-friendly formulations dispersed in water were both found to be more palatable than the existing formulation of PZQ. There may be gender and age effects on the assessment of palatability.\n\nFundingThis study was funded by Merck KGaA, Darmstadt, Germany and the Global Health Innovative Technology (GHIT) Fund (Grant nos. 2013-212).\n\nAuthor summarySchistosomiasis or Bilharzia is among top debilitating parasitic diseases in endemic developing countries. It presents in two forms of either urinary or intestinal form. The diseases mode of transmission is waterborne through contact with infested water. The main group being affected in developing countries are women and children due to their frequent contact with water. WHO introduced mass drug administration program whereby drugs are distributed in endemic communities to cut off the transmission of NTDs schistosomiasis included.\n\nPraziquantel is the sole drug for treatment of all forms of Schistosomiasis currently and it has still been proven to be highly efficacious. Preventive chemotherapy program of WHO uses the same drug as a prophylactic tool to control the disease.\n\nThe biggest challenge for this drug is its availability as a 600mg tablet with a slightly bigger size and unpleasant taste, especially for younger children. This makes uneasy administering the correct dosage of drug to school children while making preschoolers totally neglected.\n\nThis study was done as swill and spit exercise (drug was not ingested) to assess the new orally disintegrating isomers of Praziquantel, L-PZQ and Rac-PZQ which have been prepared as a 150mg tablet and improved taste as compared to the existing Praziquantel formulation. Findings from 48 African children showed that both new formulations are more palatable to younger children as compared to the existing Praziquantel formulation.\n\nThese results provide evidence for further evaluation of the clinical efficacy and tolerability of the newer formulations towards the introduction of paediatric friendly Praziquantel tablets for Schistosomiasis treatment.

epidemiology↗