Re-assessing the risk of undetected HBV, HCV and HIV in deceased tissue and living surgical bone donors in England.

Testing of living surgical bone and deceased tissue donors by NHS Blood and Transplant (NHSBT) has included individual donation (ID) nucleic acid testing (NAT) for HBV, HCV and HIV since 2008. Here, the well-established window period methodology was used to estimate residual risk (RR). Prevalence of viral markers was calculated among both tissue donor populations. Incidence was derived by adjusting incidence among new blood donors by the prevalence ratio for tissue and new blood donors. Residual risk (RR) was calculated as the product of incidence and duration of WP for single donor HBV NAT at 0.058 years (21 days), HCV NAT at 0.008 years (3 days) and HIV NAT at 0.014 (5 days). Between 2013 and 2017, 7886 living surgical bone donors were tested, 16 were positive for markers of HBV, HCV and HIV. HCV had the highest prevalence at 114/100,000 donors. Incidence and RR was highest for HBV at 3.55/100,000-person years and 0.32/100,000 donors (95% CI 0.11/100,000-1.42/100,000). Among 9751 deceased tissue donors tested, 22 were positive for viral markers. HBV had highest prevalence at 174/100,000 donors, and the highest incidence and RR at 8.12/100,000 person years and 0.74/100,000 donors (95% CI 0.08/100,000-2.99/100,000). Using ID NAT, RR of not detecting a HBV, HCV and HIV WP donation among tissue donors is less than 1/100,000 donors. These estimates provide a good starting point for discussing potential risks of viral transmission through tissue transplant with patients.

Analytical estimations of temperature in a living tissue generated by laser irradiation using experimental data.

This paper presents an analytical approach associated with Laplace transformation, experimental temperature data, and a sequential concept over time to obtain the thermal damage and the temperature in a living tissue due to laser irradiation. The analytical solutions in the Laplace domain are appreciably obtainable. The thermal damage to the tissue is completely assessed by the denatured protein range using the formulation of Arrhenius. Numerical outcomes for temperatures and the thermal damages are graphically introduced. Besides, the comparison between the numerical computations and the existing experimental study shows that a current mathematical model is an effective tool for evaluating the biological heat transfer in biological tissues.

Numerical study on the effects of blood perfusion and body metabolism on the temperature profile of human forearm in hyperthermia conditions.

The development of mathematical models for describing the thermal behavior of living tissues under normal or hyperthermia conditions is of increasing importance. In this research, a 3D forearm model based on anthropometric measurement of 25 samples in Tehran, Iran was developed. The tissue temperature distribution is obtained via the Finite Volume Method (FVM) by considering the appropriate boundary conditions, blood perfusion, body metabolism, and the application of hyperthermia conditions on the tissue. The Pennes Bioheat Transfer Equation (PBHTE) is considered in this regard. Also, various thermophysical properties are assumed for the model in order to clarify the effects of such parameters on the tissue temperature distribution. The results of this study indicate that it is possible to provide the desired conditions for many therapeutic processes by controlling the parameters such as blood perfusion, body metabolism and the type of external heat source applied on the tissue. Generally, by decreasing the body metabolism, increasing the blood perfusion rate in tissue and applying a fluctuating heat flux, instead of uniform heat flux on the surface of the forearm skin, it is possible to provide the hyperthermia conditions without causing damages such as burn injuries to the other parts of the tissue. By using the results of this study, the appropriate conditions of hyperthermia can be obtained.

A revised approach for an exact analytical solution for thermal response in biological tissues significant in therapeutic treatments.

The genesis of the present research paper is to develop a revised exact analytical solution of thermal profile of 1-D Pennes' bioheat equation (PBHE) for living tissues influenced in thermal therapeutic treatments. In order to illustrate the temperature distribution in living tissue both Fourier and non-Fourier model of 1-D PBHE has been solved by 'Separation of variables' technique. Till date most of the research works have been carried out with the constant initial steady temperature of tissue which is not at all relevant for the biological body due to its nonhomogeneous living cells. There should be a temperature variation in the body before the therapeutic treatment. Therefore, a coupled heat transfer in skin surface before therapeutic heating must be taken account for establishment of exact temperature propagation. This approach has not yet been considered in any research work. In this work, an initial condition for solving governing differential equation of heat conduction in biological tissues has been represented as a function of spatial coordinate. In a few research work, initial temperature distribution with PBHE has been coupled in such a way that it eliminates metabolic heat generation. The study has been devoted to establish the comparison of thermal profile between present approach and published theoretical approach for particular initial and boundary conditions inflicted in this investigation. It has been studied that maximum temperature difference of existing approach for Fourier temperature distribution is 19.6% while in case of non-Fourier, it is 52.8%. We have validated our present analysis with experimental results and it has been observed that the temperature response based on the spatial dependent variable initial condition matches more accurately than other approaches.

A novel 3D high-content assay identifies compounds that prevent fibroblast invasion into tissue surrogates.

Invasion processes underlie or accompany several pathological processes but only a limited number of high-throughput capable phenotypic models exist to test anti-invasive compounds in vitro. We here evaluated 3D co-cultures as a high-content phenotypic screening system for fibrotic invasive processes. 3D multicellular spheroids were used as living tissue surrogates in co-culture with fluorescently labeled lung fibroblasts to monitor invasion processes by automated microscopy. This setup was used to screen a compound library containing 480 known bioactive substances. Identified hits prevented fibroblast invasion and could be subdivided into two hit classes. First, Prostaglandins were shown to prevent fibroblast invasion, most likely mediated by the prostaglandin EP2 receptor and generation of cAMP. Additionally, Rho-associated protein kinase (ROCK) inhibitors prevented fibroblast invasion, possibly by inactivation of myosin II. Importantly, both Prostaglandins and ROCK inhibitors are potential treatment options shown to be effective in in vitro and in vivo models of fibrotic diseases. This validates the presented novel phenotypic screening approach for the evaluation of potential inhibitors and the identification of novel compounds with activity in diseases that are associated with fibroblast invasion.

Intravital biobank and personalized cancer therapy: the correlation with omics.

Biobanks have played a decisive role in all aspects of the field of cancer, including pathogenesis, diagnosis, prognosis and treatment. The significance of cancer biobanks is epitomized through the appropriate application of various "-omic" techniques (omics). The mutually motivated relationship between biobanks and omics has intensified the development of cancer research. Human cancer tissues that are maintained in intravital biobanks (or living tissue banks) retain native tumor microenvironment, tissue architecture, hormone responsiveness and cell-to-cell signalling properties. Intravital biobanks replicate the structural complexity and heterogeneity of human cancers, making them an ideal platform for preclinical studies. The application of omics with intravital biobanks renders them more active, which makes it possible for the cancer-related evaluations to be dynamically monitored on a real-time basis. Integrating intravital biobank and modern omics will provide a useful tool for the discovery and development of new drugs or novel therapeutic strategies. More importantly, intravital biobanks may play an essential role in the creation of meaningful patient-tailored therapies as for personalized medicine.

Functionalization of in vivo tissue-engineered living biotubes enhance patency and endothelization without the requirement of systemic anticoagulant administration.

Vascular regeneration and patency maintenance, without anticoagulant administration, represent key developmental trends to enhance small-diameter vascular grafts (SDVG) performance. In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties. However, mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs. Previously fabricated poly(ε-caprolactone) skeleton-reinforced biotubes (PBs) circumvented mechanical issues and achieved vascular regeneration, but orally administered anticoagulants were required. Here, highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens. The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (DMPE)-PEG-conjugated anti-coagulant bivalirudin (DPB) and DMPE-PEG-conjugated endothelial progenitor cell (EPC)-binding TPS-peptide (DPT) modifications possessed functionality conducive to promoting vascular graft patency. Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability. DPB repellent of non-specific proteins, DPB inhibition of thrombus formation, and DPB protection against functional masking of DPT's EPC-capture by blood components, which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration. This strategy offers a safe, facile, and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.

Hydrogel Bioinks of Alginate and Curcumin-Loaded Cellulose Ester-Based Particles for the Biofabrication of Drug-Releasing Living Tissue Analogs.

3D bioprinting is a versatile technique that allows the fabrication of living tissue analogs through the layer-by-layer deposition of cell-laden biomaterials, viz. bioinks. In this work, composite alginate hydrogel-based bioinks reinforced with curcumin-loaded particles of cellulose esters (CEpCUR) and laden with human keratinocytes (HaCaT) are developed. The addition of the CEpCUR particles, with sizes of 740 ± 147 nm, improves the rheological properties of the inks, increasing their shear stress and viscosity, while preserving the recovery rate and the mechanical and viscoelastic properties of the resulting fully cross-linked hydrogels. Moreover, the presence of these particles reduces the degradation rate of the hydrogels from 26.3 ± 0.8% (ALG) to 18.7 ± 1.3% (ALG:CEpCUR_10%) after 3 days in the culture medium. The 3D structures printed with the ALG:CEpCUR inks reveal increased printing definition and the ability to release curcumin (with nearly 70% of cumulative release after 24 h in PBS). After being laden with HaCaT cells (1.2 × 106 cells mL-1), the ALG:CEpCUR bioinks can be successfully 3D bioprinted, and the obtained living constructs show good dimensional stability and high cell viabilities at 7 days post-bioprinting (nearly 90%), confirming their great potential for application in fields like wound healing.

Embedded bioprinting for designer 3D tissue constructs with complex structural organization.

3D bioprinting has been developed as an effective and powerful technique for the fabrication of living tissue constructs in a well-controlled manner. However, most existing 3D bioprinting strategies face substantial challenges in replicating delicate and intricate tissue-specific structural organizations using mechanically weak biomaterials such as hydrogels. Embedded bioprinting is an emerging bioprinting strategy that can directly fabricate complex structures derived from soft biomaterials within a supporting matrix, which shows great promise in printing large vascularized tissues and organs. Here, we provide a state-of-the-art review on the development of embedded bioprinting including extrusion-based and light-based processes to manufacture complex tissue constructs with biomimetic architectures. The working principles, bioinks, and supporting matrices of embedded printing processes are introduced. The effect of key processing parameters on the printing resolution, shape fidelity, and biological functions of the printed tissue constructs are discussed. Recent innovations in the processes and applications of embedded bioprinting are highlighted, such as light-based volumetric bioprinting and printing of functional vascularized organ constructs. Challenges and future perspectives with regard to translating embedded bioprinting into an effective strategy for the fabrication of functional biological constructs with biomimetic structural organizations are finally discussed. STATEMENT OF SIGNIFICANCE: It is still challenging to replicate delicate and intricate tissue-specific structural organizations using mechanically-weak hydrogels for the fabrication of functional living tissue constructs. Embedded bioprinting is an emerging 3D printing strategy that enables to produce complex tissue structures directly inside a reservoir filled with supporting matrix, which largely widens the choice of bioprinting inks to ECM-like hydrogels. Here we aim to provide a comprehensive review on various embedded bioprinting techniques mainly including extrusion-based and light-based processes. Various bioinks, supporting matrices, key processing parameters as well as their effects on the structures and biological functions of resultant living tissue constructs are discussed. We expect that it can provide an important reference and generate new insights for the bioprinting of large vascularized tissues and organs with biological functions.

Bioprinted living tissue constructs with layer-specific, growth factor-loaded microspheres for improved enthesis healing of a rotator cuff.

Substantial challenges remain in constructing the native tendon-to-bone interface for rotator cuff healing owing to the enthesis tissues' highly organized structural and compositional gradients. Herein, we propose to bioprint living tissue constructs with layer-specific growth factors (GFs) to promote enthesis regeneration by guiding the zonal differentiation of the loaded stem cells in situ. The sustained release of tenogenic, chondrogenic, and osteogenic GFs was achieved via microsphere-based delivery carriers embedded in the bioprinted constructs. Compared to the basal construct without GFs, the layer-specific tissue analogs realized region-specific differentiation of stem cells in vitro. More importantly, bioprinted living tissue constructs with layer-specific GFs rapidly enhanced the enthesis regeneration in a rabbit rotator cuff tear model in terms of biomechanical restoration, collagen deposition, and alignment, showing gradient interface of fibrocartilage structures with aligned collagen fibrils and an ultimate load failure of 154.3 ± 9.5 N resembling those of native enthesis tissues in 12 weeks. This exploration provides a feasible strategy to engineer living tissue constructions with region-specific differentiation potentials for the functional repair of gradient enthesis tissues. STATEMENT OF SIGNIFICANCE: Previous studies that employed acellular layer-specific scaffolds or stem cells for the reconstruction of the rotator cuff faced challenges due to their insufficient capability to rebuild the anisotropic compositional and structural gradients of native enthesis tissues. This manuscript proposed a living tissue construct with layer-specific, GFs-loaded µS, which can direct in situ and region-specific differentiation of the embedded stem cells to tenogenic, chondrogenic, and osteogenic lineages for functional regeneration of the enthesis tissues. This bioprinted living tissue construct with the unique capability to reduce fibrovascular scar tissue formation and simultaneously facilitate enthesis tissue remodeling might provide a promising strategy to repair complex and gradient tissues in the future.

Biomechanics of Pulmonary Autograft as Living Tissue: A Systematic Review.

INTRODUCTION: The choice of valve substitute for aortic valve surgery is tailored to the patient with specific indications and contraindications to consider. The use of an autologous pulmonary artery (PA) with a simultaneous homograft in the pulmonary position is called a Ross procedure. It permits somatic growth and the avoidance of lifelong anticoagulation. Concerns remain on the functionality of a pulmonary autograft in the aortic position when exposed to systemic pressure. METHODS: A literature review was performed incorporating the following databases: Pub Med (1996 to present), Ovid Medline (1958 to present), and Ovid Embase (1982 to present), which was run on 1 January 2022 with the following targeted words: biomechanics of pulmonary autograft, biomechanics of Ross operation, aortic valve replacement and pulmonary autograph, aortic valve replacement and Ross procedure. To address the issues with heterogeneity, studies involving the pediatric cohort were also analyzed separately. The outcomes measured were early- and late-graft failure alongside mortality. RESULTS: a total of 8468 patients were included based on 40 studies (7796 in pediatric cohort and young adult series and 672 in pediatric series). There was considerable experience accumulated by various institutions around the world. Late rates of biomechanical failure and mortality were low and comparable to the general population. The biomechanical properties of the PA were superior to other valve substitutes. Mathematical and finite element analysis studies have shown the potential stress-shielding effects of the PA root. CONCLUSION: The Ross procedure has excellent durability and longevity in clinical and biomechanical studies. The use of external reinforcements such as semi-resorbable scaffolds may further extend their longevity.

Effects of endovenous laser ablation on vascular tissue: molecular genetics approach.

BACKGROUND: Endovenous laser ablation (EVLA) is a treatment option for lower extremity varicose veins. In the present study, we investigate to the genetic changes and possibility of living tissue in the saphenous vein wall after the EVLA procedure. METHODS: Eleven saphenous vein grafts were randomized in two groups: (1) 4 cm SVG segments of performed EVLA procedure in study group, (2) 4 cm segments of SVG none performed EVLA procedure in control group. SVG were taken from the remnants of distal saphenous vein grafts prepared for the bypass procedure but not used. SVG was approximately 8 cm in length and was divided into two parts 4 cm in length. One half was exposed to laser energy, while the other half of the same vein graft was untreated as a control. EVLA was performed on complete saphenous veins in the study group. Abnormal genetic changes of the SVG were observed with a Tri-Reagent method and quantified with a Nanodrop™ spectrophotometer. RESULTS: Histopathological changes indicated that the intima including the endothelium was completely necrotized in the study group. It was observed that intimal thermal-energy-induced injury did not reach the media. Histopathological examination showed that homogenous eosinophilic discoloration and coagulation necrosis characterized the laser related thermal damage as well. CONCLUSIONS: In this preliminary study, we found that living tissue remained in the SVG wall after application of laser ablation, and we also detected abnormal genetic changes in the study group compared with the control group.

Animal models for bladder cancer: The model establishment and evaluation (Review).

Bladder cancer is the most common type of tumor in the urogenital system. Approximately 75% of patients with bladder cancer present with non-muscle-invasive cancer, which is generally treated by transurethral resection and intravesical chemotherapy. In spite of different therapeutic options, there remains a very variable risk of recurrence and progression. Novel therapeutic methods of treating bladder cancer are urgently required. The exploration and preclinical evaluation of new treatments requires an animal tumor model that mimics the human counterpart. Animal models are key in bladder cancer research and provide a bridge to the clinic. Various animal bladder cancer models have been described to date, but the tumor take rate is reported to be 30-100%. Establishment of reliable, simple, practicable and reproducible animal models remains an ongoing challenge. The present review summarizes the latest developments with regard to the establishment of animal models and tumor evaluation.

Time-domain Photoacoustic Tomography of Mouse Brain Vessel in Vivo / 医疗卫生装备

Objective To get photoacoustic (PA) image of vascular structure inside mouse brain in vivo.Methods A 532nm pulsed laser was used as the pumping source to generate PA signal,and a wide-band PVDF unfocused ultrasound transducer was used to collect time-domain PA signal by circular scan.PA signal recorded at each scanning position was then de-noised by wavelets transform using soft-thresholding.The PA image of the mouse brain vessel was reconstructed by time-domain spherical back projection algorithm.Results PA image agreed well with the histological picture of mouse brain vessel.Conclusion The experimental result indicates the potential value of clinical application.