Currently, patients with end-stage lung disease are limited to lung transplantation as their only treatment option. Unfortunately, the lungs available for transplantation are few. Moreover, transplant recipients require life-long immune suppression to tolerate the transplanted lung. A promising alternative therapeutic strategy is decellularization of whole lungs, which permits the isolation of an intact scaffold comprised of innate extracellular matrix (ECM) that can theoretically be recellularized with autologous stem or progenitor cells to yield a functional lung. Nonhuman primates (NHP) provide a highly relevant preclinical model with which to assess the feasibility of recellularized lung scaffolds for human lung transplantation. Our laboratory has successfully accomplished lung decellularization and initial stem cell inoculation of the resulting ECM scaffold in an NHP model. Decellularization of normal adult rhesus macaque lungs as well as the biology of the resulting acellular matrix have been extensively characterized. Acellular NHP matrices retained the anatomical and ultrastructural properties of native lungs with minimal effect on the content, organization, and appearance of ECM components, including collagen types I and IV, laminin, fibronectin, and sulfated glycosaminoglycans (GAG), due to decellularization. Proteomics analysis showed enrichment of ECM proteins in total tissue extracts due to the removal of cells and cellular proteins by decellularization. Cellular DNA was effectively removed after decellularization (∼92% reduction), and the remaining nuclear material was found to be highly disorganized, very-low-molecular-weight fragments. Both bone marrow- and adipose-derived mesenchymal stem cells (MSC) attach to the decellularized lung matrix and can be maintained within this environment in vitro, suggesting that these cells may be promising candidates and useful tools for lung regeneration. Analysis of decellularized lung slice cultures to which MSC were seeded showed that the cells attached to the decellularized matrix, elongated, and proliferated in culture. Future investigations will focus on optimizing the recellularization of NHP lung scaffolds toward the goal of regenerating pulmonary tissue. Bringing this technology to eventual human clinical application will provide patients with an alternative therapeutic strategy as well as significantly reduce the demand for transplantable organs and patient wait-list time.

/pdf/a-nonhuman-primate-model-of-lung-regeneration-detergent-1wrqbn5v5m.pdf

A Nonhuman Primate Model of Lung Regeneration: Detergent-Mediated Decellularization and Initial In Vitro Recellularization with Mesenchymal Stem Cells

Decellularized heart ECM hydrogel using supercritical carbon dioxide for improved angiogenesis.

In the present work, magnesium (Mg) AZ31 alloy was coated with a multifunctional membrane layer composed of ZnO nanoparticles (NPs) embedded in a poly(lactic acid) (PLA) matrix. We aimed to produce a stable coating that would be used to control the degradation rate of the Mg alloy and promote a local antibacterial activity. ZnO NPs were dispersed at 5 and 10 wt % in a PLA solution and dip-coated onto the AZ31 substrate. Surface topography, chemical composition, thickness, electrochemical corrosion performance, mass variation, antibacterial activity, adhesion performance, and cytotoxicity of an uncoated control and coated alloys were investigated. The results indicated that the incorporation of ZnO NPs at various concentrations affords a dramatic control over surface topography and degradation rates under in vitro and in vivo environmental conditions when compared to the uncoated Mg alloy control. In addition, the results confirmed that the coated layer exerts antibacterial properties and supports cell gro...

A Multifunctional Zinc Oxide/Poly(Lactic Acid) Nanocomposite Layer Coated on Magnesium Alloys for Controlled Degradation and Antibacterial Function.

Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting techniques and other procedures in which healing is slow, there is a high risk of infection and considerable pain is provoked - with no guarantee of complete correction of the defect. Therefore, the search for surgical alternatives continues to present a major challenge in orthopaedic traumatology. The reamer-irrigator-aspirator (RIA) system, which was devised to avoid the problems that can arise with autograft harvesting from the iliac crest, consists of collecting the product of the femoral canal after reaming. The RIA technique improves osteogenic differentiation of mesenchymal stem cells, compared to bone marrow aspiration or cancellous bone harvesting from the iliac crest using a spoon. Another approach, the Masquelet technique, consists of reconstructing a long bone defect by means of an induced membrane grown onto an acrylic cement rod inserted to fill the defect; in a second surgical step, once the membrane is constituted, the cement rod is removed and cancellous autograft is used to fill the defect. Both in RIA and in the Masquelet technique, osteosynthesis is usually needed. Bone transportation by compression-distraction lengthening principles is commonly implemented for the treatment of large bone loss. However, complications are frequently encountered with these techniques. Among new techniques that have been proposed to address the problem of large bone loss, the application of stem cells in conjunction with tissue engineering techniques is very promising, as is the creation of personalised medicine (or precision medicine), in which molecular profiling technologies are used to tailor the therapeutic strategy, to ensure the right method is applied for the right person at the right time, after determining the predisposition to disease among the general population. All of the above techniques for addressing bone defects are discussed in this paper.

Challenges of bone tissue engineering in orthopaedic patients.

This review presents the different combination methods of 3D printing and electrospinning processes and discusses the advantages of each method. Also, the applications of products of the hybrid process in the biomedical field, including tissue engineering and regenerative medicine, are thoroughly discussed. 3D printing and electrospinning are separate approaches for generating structured materials in a variety of biomedical applications. However, some shortfalls, such as the low resolution of 3D printing and uncontrollable shape of electrospun products, limits their application performances. Therefore, new ideas that combine 3D printing and electrospinning methods are proposed to give full play to their strengths and mitigate their weaknesses, which provide an effective and powerful platform for fabricating novel structural materials. Finally, a future vision regarding challenges and perspectives in the combination of 3D printing and electrospinning techniques is proposed.

Combination of 3D Printing and Electrospinning Techniques for Biofabrication

Retraction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

/pdf/retraction-experimental-orthotopic-transplantation-of-a-2xl5cwkght.pdf

Retraction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats.

A nExperimenta lAnima lMode lo fPostobstructive Pulmonar yHypertension

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi.

/pdf/experimental-orthotopic-transplantation-of-a-tissue-14ya7gs8s3.pdf

Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

Development of novel prognostic, diagnostic, and treatment options will provide major benefits for millions of patients with acute or chronic respiratory dysfunction, cardiac-related disorders, esophageal problems, or other diseases in the thorax. Allogeneic organ transplant is currently available. However, it remains a trap because of its dependency on a very limited supply of donated organs, which may be needed for both initial and subsequent transplants. Furthermore, it requires lifelong treatment with immunosuppressants, which are associated with adverse effects. Despite early clinical applications of bioengineered organs and tissues, routine implementation is still far off. For this review, we searched the PubMed, MEDLINE, and Ovid databases for the following keywords for each tissue or organ: tissue engineering, biological and synthetic scaffold/graft, acellular and decelluar(ized), reseeding, bioreactor, tissue replacement, and transplantation. We identified the current state-of-the-art practices in tissue engineering with a focus on advances during the past 5 years. We discuss advantages and disadvantages of biological and synthetic solutions and introduce novel strategies and technologies for the field. The ethical challenges of innovation in this area are also reviewed.

/pdf/whole-organ-and-tissue-reconstruction-in-thoracic-36syov7o89.pdf

Whole organ and tissue reconstruction in thoracic regenerative surgery.

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Retraction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats.

A nExperimenta lAnima lMode lo fPostobstructive Pulmonar yHypertension

Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

Whole organ and tissue reconstruction in thoracic regenerative surgery.