Imatinib pharmacokinetics and creatine kinase levels in chronic myeloid leukemia patients: implications for therapeutic response and monitoring.

BACKGROUND: Imatinib treatment for certain cancers can lead to elevated creatine kinase (CK) levels, potentially indicating muscle injury, and ongoing research aims to understand the correlation between imatinib levels and creatine kinase to assess its impact on treatment response. METHODS: This single-center observational study involved 76 chronic myeloid leukemia (CML) patients receiving imatinib treatment, focusing on evaluating drug and metabolite levels using liquid chromatography-mass spectrometry (LC-MS-MS) instrumentation. Serum CK and creatine kinase-MB (CK-MB) levels were assessed using Colorimetric kits. RESULTS: CK and CK-MB levels were measured, CK showed a median value of 211.5 IU/l and CK-MB showed a median value of 4.4 IU/l. Comparing low and high CK groups, significant differences were found in peak and trough plasma concentrations of imatinib and its metabolites. Correlations between CK levels and pharmacokinetic parameters were explored, with notable associations identified. Binary logistic regression revealed predictors influencing the therapeutic response to imatinib and categorized expected CK levels into high or low, with peak levels of imatinib emerging as a significant predictor for CK level categorization. CONCLUSION: The study highlights the link between imatinib's pharmacokinetics and elevated CK levels, indicating a possible correlation between specific metabolites and improved treatment response. Individualized monitoring of CK levels and imatinib pharmacokinetics could enhance care for CML patients.

Assessment of some chemical residues in Egyptian raw milk and traditional cheese.

Background: The assessment of risks related to food safety is becoming a challenge in developing countries with its consequent health hazards. Chemical risk assessment in dairy products is important to maintain consumer health locally and internationally. Since milk and dairy products are essential foods for a wide range of customers, mostly children, patients, and pregnant women, it is very important to estimate the risks of some chemical residues, such as pesticides, some heavy metals, and aflatoxins. Aim: This work aims to determine the levels of chemical contamination in milk and traditional Egyptian cheese. Methods: Heavy metals were determined in samples by atomic absorption spectrometry. GC-mass spectrometry (MS)/MS and LC-MS/MS were also used for measuring pesticide residues. The Aflatoxin M1 was determined by enzyme-linked immune-sorbent assay. Results: Raw milk samples were tested and showed elevated concentrations of lead and cadmium, (46% and 4%, respectively). The heavy metals detected in the Egyptian cheese samples were variable depending on the type of cheese. Moreover, p.p.-DDE phenofose was present in 45% and 29% of raw milk and Ras cheese samples, respectively. For Aflatoxin M1, only 7% of milk samples and 2.9% of Ras cheese samples exceeded the acceptable limits. Conclusion: More surveying and risk assessment of chemical residues in milk and milk products are essential for controlling health risks to consumers.

Relationship between the Dynamics of Flavor Compounds and Microbial Succession in the Natural Fermentation of Zhalajiao, a Popular Traditional Chinese Fermented Chili Paste.

Zhalajiao, a traditional Chinese fermented food, is popular due to its unique flavor. Traditional Zhalajiao fermentation is closely related to flavor compounds production. However, the mechanisms underlying the formation of these crucial flavor components in Zhalajiao remain unclear. Here, we explored the dynamic changes in physical and chemical properties, microbial diversity, and flavor components of Zhalajiao at various fermentation times. In total, 6 organic acids, 17 amino acids, and 21 key volatile compounds were determined as flavor components. In Zhalajiao, Lactobacillus and Cyanobacterium were the main bacteria that were involved in the formation of crucial flavor compounds. Candida showed a significant correlation with 14 key flavor compounds during fermentation (p < 0.05) and was the main fungal genus associated with flavor formation in Zhalajiao. This research offers a theoretical foundation for the flavor regulation and quality assurance of Zhalajiao.

Mechanical and morphological properties of parietal bone in patients with sagittal craniosynostosis.

Limited information is available on the effect of sagittal craniosynostosis (CS) on morphological and material properties of the parietal bone. Understanding these properties would not only provide an insight into bone response to surgical procedures but also improve the accuracy of computational models simulating these surgeries. The aim of the present study was to characterise the mechanical and microstructural properties of the cortical table and diploe in parietal bone of patients affected by sagittal CS. Twelve samples were collected from pediatric patients (11 males, and 1 female; age 5.2 ± 1.3 months) surgically treated for sagittal CS. Samples were imaged using micro-computed tomography (micro-CT); and mechanical properties were extracted by means of micro-CT based finite element modelling (micro-FE) of three-point bending test, calibrated using sample-specific experimental data. Reference point indentation (RPI) was used to validate the micro-FE output. Bone samples were classified based on their macrostructure as unilaminar or trilaminar (sandwich) structure. The elastic moduli obtained using RPI and micro-FE approaches for cortical tables (ERPI 3973.33 ± 268.45 MPa and Emicro-FE 3438.11 ± 387.38 MPa) in the sandwich structure and diploe (ERPI1958.17 ± 563.79 MPa and Emicro-FE 1960.66 ± 492.44 MPa) in unilaminar samples were in strong agreement (r = 0.86, p < .01). We found that the elastic modulus of cortical tables and diploe were correlated with bone mineral density. Changes in the microstructure and mechanical properties of bone specimens were found to be irrespective of patients' age. Although younger patients are reported to benefit more from surgical intervention as skull is more malleable, understanding the material properties is critical to better predict the surgical outcome in patients <1 year old since age-related changes were minimal.

Effect of l-carnitine on cardiotoxicity and apoptosis induced by imatinib through PDGF/ PPARγ /MAPK pathways.

A tyrosine kinase inhibitor Imatinib (IM) is used in the treatment of different varieties of cancers. The current study was designed to explore the beneficial role of l-carnitine against IM-induced cardiotoxicity in rats. Male albino rats received IM (40 mg/kg, i.p.) either alone or/in combination with l-carnitine (100 mg/kg, i.p.) for 7 days. IM increased serum inflammatory cytokines, concomitant with activation of cardiac MAPK, α-SMA, malondialdehyde (MDA) and nitric oxide(NO), decreased cardiac peroxisome proliferator-activated receptor-γ (PPAR-γ) level, superoxide dismutase (SOD) activity, and glutathione (GSH) content. The expression levels of Bcl-2 and PDGF were significantly decreased, while the expression levels of CTGF and BAX were significantly increased in the IM group. The l-carnitine treatment successfully protected the heart as indicated by the improvement of the biochemical and histopathological parameters. l-carnitine didn't affect the serum concentration of IM and increased intracellular concentration in the combination-treated group as measured by the mass spectrometer. Conclusion: l-carnitine abrogated IM-induced cardiac damage and apoptosis via PDGF/PPARγ/MAPK pathways.

WE43 and WE43-T5 Mg alloys screws tested in-vitro cellular adhesion and differentiation assay and in-vivo histomorphologic analysis in an ovine model.

WE43 Mg alloy proved to be an ideal candidate for production of resorbable implants in both clinical and trial settings. In previous studies we tested biocompatibility and degradation properties of WE43 (as-cast) and artificially aged (WE43-T5) Mg alloys in a sheep model. Both alloys showed excellent biocompatibility with the as-cast, WE43, form showing increased degradability compared to the artificially aged, WE43-T5. In the present study, our group assessed the biological behavior and degradation pattern of the same alloys when implanted as endosteal implants in a sheep model. Twelve screws (3x15 mm) were evaluated, one screw per each composition was placed bi-cortically in the mandible of each animal with a titanium (2x12 mm) screw serving as an internal positive control. At 6 and 24 weeks histomorphological analysis was performed, at 6 weeks as cast, WE43, yielded a higher degradation rate, increased bone remodeling and osteolysis compared to the WE43-T5 alloy; however, at 24 weeks WE43-T5 showed higher degradation rate and increased bone remodeling than as-cast. In vitro assay of cell growth, adhesion and differentiation was also conducted to investigate possible mechanisms underlying the behavior expressed from the alloys in vivo. In conclusion WE43-T5 indicated bone/implant interaction properties that makes it more suitable for fabrication of endosteal bone screws.

Three-dimensional environment and vascularization induce osteogenic maturation of human adipose-derived stem cells comparable to that of bone-derived progenitors.

While human adipose-derived stem cells (hADSCs) are known to possess osteogenic differentiation potential, the bone tissues formed are generally considered rudimentary and immature compared with those made by bone-derived precursor cells such as human bone marrow-derived mesenchymal stem cells (hBMSCs) and less commonly studied human calvarium osteoprogenitor cells (hOPs). Traditional differentiation protocols have tended to focus on osteoinduction of hADSCs through the addition of osteogenic differentiation media or use of stimulatory bioactive scaffolds which have not resulted in mature bone formation. Here, we tested the hypothesis that by reproducing the physical as well as biochemical bone microenvironment through the use of three-dimensional (3D) culture and vascularization we could enhance osteogenic maturation in hADSCs. In addition to biomolecular characterization, we performed structural analysis through extracellular collagen alignment and mineral density in our bone tissue engineered samples to evaluate osteogenic maturation. We further compared bone formed by hADSCs, hBMSCs, and hOPs against mature human pediatric calvarial bone, yet not extensively investigated. Although bone generated by all three cell types was still less mature than native pediatric bone, a fibrin-based 3D microenvironment together with vascularization boosted osteogenic maturation of hADSC making it similar to that of bone-derived osteoprogenitors. This demonstrates the important role of vascularization and 3D culture in driving osteogenic maturation of cells easily available but constitutively less committed to this lineage and suggests a crucial avenue for recreating the bone microenvironment for tissue engineering of mature craniofacial bone tissues from pediatric hADSCs, as well as hBMSCs and hOPs.

Molecular Detection of Occult Hepatitis B virus in plasma and urine of renal transplant patients in Khartoum state Sudan.

OBJECTIVE: The aim of this study was to determine the OBI in plasma and urine samples from renal transplant patients using Multiplex Nested PCR. METHOD: A total of 100 samples (plasma and urine) were collected from renal transplant patients admitted to the renal transplant center in Khartoum north, Sudan in 2019. For each sample, HBsAg, HBeAg and anti HBcAg were detected using Enzyme linked Immune sorbent assay (ELISA). The viral DNA was then extracted using viral DNA extraction kit and were then tested for HBV DNA by using multiplex nested PCR. Statistical analysis was done using statistical package of social science (IBM SPSS version 20.0) considering a P value ≤ 0.05 as a level of significance. RESULTS: HBsAg were not detected in al patient but, HBeAg were 14 (14%) and anti HBcAg were 36 (36%)were detect by using ELISA. A total 18 (18%) and 3 out of 100 were found positive in plasma and urine samples, respectively. Regarding the virus genotypes, D, E and mixed D/E genotypes were detected in all positive samples. Females were significantly (P value=0.013) higher detectable with HBV than males in plasma samples CONCLUSION: OBI incidence in renal transplant patients is high in Sudan. The multiplex nested PCR had identified OBI with a high rate supporting the efficiency of using molecular techniques in detecting of HBV. This will lead to an appropriate diagnosis and minimizing the risk to be infected by HBV.

Dipyridamole-loaded 3D-printed bioceramic scaffolds stimulate pediatric bone regeneration in vivo without disruption of craniofacial growth through facial maturity.

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (ß -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.

Evaluation of tamoxifen and simvastatin as the combination therapy for the treatment of hormonal dependent breast cancer cells.

Tamoxifen (TAM) is a nonsteroidal antiestrogen drug, used in the prevention and treatment of all stages of hormone-responsive breast cancer. Simvastatin (SIM), a lipid-lowering agent, has been shown to inhibit cancer cell growth. The study aimed at investigating the impact of using SIM with TAM in estrogen receptor-positive (ER+) breast cancer cell line, T47D, as well as in mice-bearing Ehrlich solid tumor. The cell line was treated with different concentrations of TAM or/and SIM for 72 h. The effects of treatment on cytotoxicity, oxidative stress markers, apoptosis, angiogenesis, and metastasis were investigated. Our results showed that the combination treatment decreased the oxidative stress markers, glucose uptake, VEGF, and MMP 2 &9 in the cell line compared to TAM- treated cells. Drug interaction of TAM and SIM was synergistic in T47D by increasing the apoptotic makers Bax/BCL-2 ratio and caspase 3 activity. Additionally, in vivo, the combination regimen resulted in a non-significant decrease in the tumor volume compared to TAM treated group. Moreover, the combined treatment decreased the protein expression of TNF-α, NF-kB compared to control. In conclusion, our results suggest that SIM may serve as a promising treatment with TAM for improving the efficacy against estrogen receptor-positive (ER+) breast cancer.

Simvastatin Evokes An Unpredicted Antagonism For Tamoxifen In MCF-7 Breast Cancer Cells.

PURPOSE: Tamoxifen (TAM) is a non-steroidal antiestrogen drug, used in the prevention and treatment of all stages of hormone-responsive breast cancer. Simvastatin (SIM) is a lipid-lowering agent and has been shown to inhibit cancer cell growth. The study aimed to investigate the effect of the combination of TAM and SIM in the treatment of estrogen receptor positive (ER+) breast cancer cell line, MCF-7, and in mice-bearing Ehrlich solid tumors. METHODS: MCF-7 cells were treated with different concentrations of TAM or/and SIM for 72 hours and the effects of the combination treatment on cytotoxicity, oxidative stress markers, apoptosis, angiogenesis, and metastasis were investigated using different techniques. In addition, tumor volume, oxidative markers, and inflammatory markers of the combined therapy were explored in mice bearing solid EAC tumors. RESULTS: The results showed that treatment of MCF-7 cells with the combination of 10 µM TAM, and 2 µM SIM significantly inhibited the increase in oxidative stress markers, LDH, and NF-kB induced by TAM. In addition, there was a significant decrease in the total apoptotic ratio, caspase-3 activity, and glucose uptake, while there was a non-significant change in Bax/bcl-2 ratio compared to the TAM-treated group. Using the isobologram equation, the drug interaction was antagonistic with combination index, CI=1.18. On the other hand, the combination regimen decreased VEGF, and matrix metalloproteinases, MMP 2&9 compared to TAM-treated cells. Additionally, in vivo, the combination regimen resulted in a non-significant decrease in the tumor volume, decreased oxidative markers, and the protein expression of TNF-α, and NF-κB compared to the TAM treated group. CONCLUSION: Although the combination regimen of TAM and SIM showed an antagonistic drug interaction in MCF-7 breast cancer, it displayed favorable antiangiogenic, anti-metastatic, and anti-inflammatory effects.

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the most commonly used osteogenic agents in the craniofacial skeleton. This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently available. METHODS: An extensive literature search was conducted. Randomized controlled trials (RCTs), case series and reports in the English language as well as Food and Drug Administration reports were reviewed. Studies were graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence Scale. Data heterogeneity precluded quantitative analysis. RESULTS: Seventeen RCTs (Levels of evidence: Ib-IIb) were identified evaluating the use of rhBMP-2 in maxillary sinus, alveolar ridge, alveolar cleft, or cranial defect reconstruction (sample size: 7-160; age: 8-75 years). Study designs varied in rigor, with follow-up ranging 3-36 months, and outcome assessment relying on clinical exam, radiology, and/or histology. There was wide variation in rhBMP-2 concentrations, carriers, and controls. Most studies evaluating rhBMP-2 for cranial defect closure, mandibular reconstruction, or distraction osteogenesis consisted of retrospective cohorts and case reports. The evidence fails to support RhBMP-2 use in maxillary sinus wall augmentation, calvarial reconstruction, mandibular reconstruction, or distraction osteogenesis. RhBMP-2 may be effective in alveolar reconstruction in adults, but is associated with increased postoperative edema. CONCLUSIONS: A risk-benefit ratio favoring rhBMP-2 over alternative substitutes remains to be demonstrated for most applications in plastic and reconstructive surgery. Long-term data on craniofacial growth is lacking, and using rhBMP-2 in patients younger than 18 years remains off-label.

Argon plasma modification promotes adipose derived stem cells osteogenic and chondrogenic differentiation on nanocomposite polyurethane scaffolds; implications for skeletal tissue engineering.

Bone and cartilage craniofacial defects due to trauma or congenital deformities pose a difficult problem for reconstructive surgeons. Human adipose stem cells (ADSCs) can differentiate into bone and cartilage and together with suitable scaffolds could provide a promising system for skeletal tissue engineering. It has been suggested that nanomaterials can direct cell behavior depending on their surface nanotopographies. Thus, this study examined whether by altering a nanoscaffold surface using radiofrequency to excite gases, argon (Ar), nitrogen (N2) and oxygen (O2) with a single step technique, we could enhance the osteogenic and chondrogenic potential of ADSCs. At 24 h, Ar modification promoted the highest increase in ADSCs adhesion as indicated by upregulation of vinculin and focal adhesion kinase (FAK) expression compared to O2 and N2 scaffolds. Furthermore, ADSCs on Ar-modified nanocomposite polymer POSS-PCU scaffolds upregulated expression of bone markers, alkaline phosphatase, collagen I and osteocalcin after 3 weeks. Cartilage markers, aggrecan and collagen II, were also upregulated on Ar-modified scaffolds at the mRNA and protein level. Finally, all plasma treated scaffolds supported tissue ingrowth and angiogenesis after grafting onto the chick chorioallantoic membrane. Ar promoted greater expression of vascular endothelial growth factor and laminin in ovo compared to O2 and N2 scaffolds as shown by immunohistochemistry. This study provides an important understanding into which surface chemistries best support the osteogenic and chondrogenic differentiation of ADSCs that could be harnessed for regenerative skeletal applications. Argon surface modification is a simple tool that can promote ADSC skeletal differentiation that is easily amenable to translation into clinical practice.

Human Leukocyte Antigen (HLA) class I and II datasets for sudanese.

Sudan is located in the heart of Africa and surrounded by eight countries with people of different ethnic origins. Historical records show that the population of the Sudan is a mixture of Arabic, West Asian Arabic and sub-Saharan African elements. The present survey provides data on allele lineages, and haplotype frequencies of Human Leukocyte Antigen (HLA) class I (HLA-A and HLA-B) and class II (HLA-DR and -HLA-DQ) loci in 11 Sudanese populations. The sampled individuals are all local transplant donors who provided informed consent for HLA analyses on their blood samples and were registered at National Cancer Institute, University of Gezira, Wad Medani. The HLA class I and II data reported here can be subjected for future analyses of genetic structure and health in Sudan. These include as reference datasets for identifying the association between HLA and diseases and for designing donor recruitment strategies.

Objectifying Micrognathia Using Three-Dimensional Photogrammetric Analysis.

BACKGROUND: Micrognathia occurs isolated and as part of entities like Robin sequence (RS). An objective measurement of mandible size and growth is needed to determine the degree of micrognathia and enable a comparison of treatment outcomes. A pilot study was conducted to investigate the usability of 3-dimensional (3D) facial photogrammetry, a fast, noninvasive method, to estimate mandible size and growth in a small cohort of newborns and infants. METHODS: Exterior mandibular volume was estimated using a tetrahedron defined by 4 facial landmarks. Twelve patients with RS with different etiologies were selected and photogrammetric images were obtained prospectively in 3 patients with RS in whom mandibular growth in the first year of life was determined. We used 3 tetrahedra defined by 6 landmarks on mandibular computed tomography (CT) scans to estimate an interior mandibular volume, which we compared to the exterior mandibular volume in 10 patients. RESULTS: The exterior mandibular volume using 3D photography could be determined in all patients. Signature heat maps allowed visualization of facial dysmorphism in 3D; signature graphs demonstrated similarities of facial dysmorphism in patients with the same etiology and differences from those with other diagnoses and from controls. The correlation between interior (3D photogrammetry) and exterior mandibular volumes (CT imaging) was 0.8789. CONCLUSION: The 3D facial photogrammetry delineates the general facial characteristics in patients with different syndromes involving micrognathia, and can objectively estimate mandibular volume and growth, with excellent correlation with bony measurement. It has been concluded that 3D facial photogrammetry could be a clinically effective instrument for delineating and quantifying micrognathia.

Cranial bone structure in children with sagittal craniosynostosis: Relationship with surgical outcomes.

BACKGROUND: While spring-assisted cranioplasty has become a widespread technique to correct scaphocephaly in children with sagittal synostosis, predicting head shape changes induced by the gradual opening of the springs remains challenging. This study aimed to explore the role of cranial bone structure on surgical outcomes. METHODS: Patients with isolated sagittal synostosis undergoing spring-assisted cranioplasty at GOSH (London, UK) were recruited (n = 18, age: 3-8 months). Surgical outcome was assessed by the change in cephalic index measured on 3D head scans acquired before spring insertion and after their removal using a 3D handheld scanner. Parietal bone samples routinely discarded during spring-assisted cranioplasty were collected and scanned using micro-computed tomography. From visual assessment of such scans, bone structure was classified into one- or three-layered, the latter indicating the existence of a diploë cavity. Bone average thickness, volume fraction and surface density were computed and correlated with changes in cephalic index. RESULTS: Cephalic index increased for all patients (p < 0.001), but individual improvement varied. Although the patient age and treatment duration were not significantly correlated with changes in cephalic index, bone structural parameters were. The increase of cephalic index was smaller with increasing bone thickness (Pearson's r = -0.79, p < 0.001) and decreasing bone surface density (r = 0.77, p < 0.001), associated with the three-layered bone structure. CONCLUSIONS: Variation in parietal bone micro-structure was associated with the magnitude of head shape changes induced by spring-assisted cranioplasty. This suggests that bone structure analysis could be a valuable adjunct in designing surgical strategies that yield optimal patient-specific outcomes.

An overview of the therapeutic potential of regenerative medicine in cutaneous wound healing.

The global burden of disease associated with wounds is an increasingly significant public health concern. Current treatments are often expensive, time-consuming and limited in their efficacy in chronic wounds. The challenge of overcoming current barriers associated with wound care requires innovative management techniques. Regenerative medicine is an emerging field of research that focuses on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function. This article provides an overview of the pathophysiology of wound healing and reviews the latest evidence on the application of the principal components of regenerative medicine (growth factors, stem cell transplantation, biomaterials and tissue engineering) as therapeutic targets. Improved knowledge and understanding of the pathophysiology of wound healing has pointed to new therapeutic targets. Regenerative medicine has the potential to underpin the design of specific target therapies in acute and chronic wound healing. This personalised approach could eventually reduce the burden of disease associated with wound healing. Further evidence is required in the form of large animal studies and clinical trials to assess long-term efficacy and safety of these new treatments.

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice.

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering "holds the promise of revolutionizing patient care in the twenty-first century." The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20-30 years from the start of basic science research to clinical utility, demonstrated by contemporary treatments such as bone marrow transplantation. Although great advances have been made in the tissue engineering field, we highlight the barriers that need to be overcome before we see the routine use of tissue-engineered solutions.

Towards reconstruction of epithelialized cartilages from autologous adipose tissue-derived stem cells.

Deformities of the upper airways, including those of the nose and throat, are typically corrected by reconstructive surgery. The use of autologous somatic stem cells for repair of defects could improve quality and outcomes of such operations. The present study explored the ability of paediatric adipose-derived stem cells (pADSCs), a readily available source of autologous stem cells, to generate a cartilage construct with a functional epithelium. Paediatric ADSCs seeded on the biodegradable nanocomposite polymer, polyhedral oligomeric silsesquioxane poly(ϵ-caprolactone-urea) urethane (POSS-PCL), proliferated and differentiated towards mesenchymal lineages. The ADSCs infiltrated three-dimensional POSS-PCL nanoscaffold and chondroid matrix was observed throughout chondrogenically induced samples. In ovo chorioallantoic membrane-grafted ADSC-nanoscaffold composites were enwrapped by host vessels indicating good compatibility in an in vivo system. Furthermore, pADSCs could be induced to transdifferentiate towards barrier-forming epithelial-like cells. By combining differentiation protocols, it was possible to generate epithelial cell lined chondrogenic micromasses from the same pADSC line. This proof-of-concept study appears to be the first to demonstrate that individual pADSC lines can differentiate towards two different germ lines and be successfully co-cultured. This has important implications for bioengineering of paediatric airways and further confirms the plastic nature of ADSCs. Copyright © 2016 John Wiley & Sons, Ltd.

Combined soft and skeletal tissue modelling of normal and dysmorphic midface postnatal development.

BACKGROUND: Midface hypoplasia as exemplified by Treacher Collins Syndrome (TCS) can impair appearance and function. Reconstruction involves multiple invasive surgeries with variable long-term outcomes. This study aims to describe normal and dysmorphic midface postnatal development through combined modelling of skeletal and soft tissues and to develop a surgical evaluation tool. MATERIALS AND METHODS: Midface skeletal and soft tissue surfaces were extracted from computed tomography scans of 52 control and 14 TCS children, then analysed using dense surface modelling. The model was used to describe midface growth, morphology, and asymmetry, then evaluate postoperative outcomes. RESULTS: Parameters responsible for the greatest variation in midface size and shape showed differences between TCS and controls with close alignment between skeletal and soft tissue models. TCS children exhibited midface dysmorphology and hypoplasia when compared with controls. Asymmetry was also significantly higher in TCS midfaces. Combined modelling was used to evaluate the impact of surgery in one TCS individual who showed normalisation immediately after surgery but reversion towards TCS dysmorphology after 1 year. CONCLUSION: This is the first quantitative analysis of postnatal midface development using combined modelling of skeletal and soft tissues. We also provide an approach for evaluation of surgical outcomes, laying the foundations for future development of a preoperative planning tool.