Melatonin induces fiber switching by improvement of mitochondrial oxidative capacity and function via NRF2/RCAN/MEF2 in the vastus lateralis muscle from both sex Zücker diabetic fatty rats.

The positive role of melatonin in obesity control and skeletal muscle (SKM) preservation is well known. We recently showed that melatonin improves vastus lateralis muscle (VL) fiber oxidative phenotype. However, fiber type characterization, mitochondrial function, and molecular mechanisms that underlie VL fiber switching by melatonin are still undefined.

Phase I-IIa clinical trial to evaluate the safety, feasibility and efficacy of the use of a palate mucosa generated by tissue engineering for the treatment of children with cleft palate: the BIOCLEFT study protocol.

Introduction: The current gold standard treatment for patients with orofacial clefts is surgical repair of the palatal defect (uranostaphylorrhaphy), which is associated with growth defects and hypoplasia of the maxillofacial structures. This trial aims to evaluate the potential of a bioengineered artificial palate mucosa, created through tissue engineering with autologous stromal and epithelial cells and nanostructured fibrin-agarose biomaterials, to enhance treatment outcomes for patients with unilateral cleft lip and palate.

Methods And Analysis: This phase I-IIa clinical trial aims to evaluate the feasibility and biosafety of a procedure involving grafting bioartificial palate mucosa onto the areas of denudated bone in patients undergoing uranostaphylorrhaphy.

Histological, histochemical, and immunohistochemical characterization of NANOULCOR nanostructured fibrin-agarose human cornea substitutes generated by tissue engineering.

Background: Human artificial corneas (HAC) generated by tissue engineering recently demonstrated clinical usefulness in the management of complex corneal diseases. However, the biological mechanisms associated to their regenerative potential need to be elucidated.

Methods: In the present work, we generated HAC using nanostructured fibrin-agarose biomaterials with cultured corneal epithelial and stromal cells, and we compared the structure and histochemical and immunohistochemical profiles of HAC with control native corneas (CTR-C) and limbus (CTR-L) to determine the level of biomimicry of the HAC with these two native organs.

Histological assessment of nanostructured fibrin-agarose skin substitutes grafted in burnt patients. A time-course study.

A previously developed fibrin-agarose skin model-UGRSKIN-showed promising clinical results in severely burnt patients. To determine the histological parameters associated to the biocompatibility and therapeutic effects of this model, we carried out a comprehensive structural and ultrastructural study of UGRSKIN grafted in severely burnt patients after 3 months of follow-up. The grafted epidermis was analogue to native human skin from day 30th onward, revealing well-structured strata with well-differentiated keratinocytes expressing CK5, CK8, CK10, claudin, plakoglobin, filaggrin, and involucrin in a similar way to controls, suggesting that the epidermis was able to mature and differentiate very early.

A novel 3D biofabrication strategy to improve cell proliferation and differentiation of human Wharton's jelly mesenchymal stromal cells for cell therapy and tissue engineering.

Obtaining sufficient numbers of cells in a short time is a major goal of cell culturing in cell therapy and tissue engineering. However, current bidimensional (2D) culture methods are associated to several limitations, including low efficiency and the loss of key cell differentiation markers on cultured cells. In the present work, we have designed a novel biofabrication method based on a three-dimensional (3D) culture system (FIBRIAGAR-3D).

Optimization of human skin keratinocyte culture protocols using bioactive molecules derived from olive oil.

Skin damage due to severe burns can compromise patient life. Current tissue engineering methods allow the generation of human skin substitutes for clinical use. However, this process is time-consuming, as the keratinocytes required to generate artificial skin have a low proliferation rate in culture.

Development of stromal differentiation patterns in heterotypical models of artificial corneas generated by tissue engineering.

We carried out a histological characterization analysis of the stromal layer of human heterotypic cornea substitutes generated with extra-corneal cells to determine their putative usefulness in tissue engineering. Human bioartificial corneas were generated using nanostructured fibrin-agarose biomaterials with corneal stromal cells immersed within. To generate heterotypical corneas, umbilical cord Wharton's jelly stem cells (HWJSC) were cultured on the surface of the stromal substitutes to obtain an epithelial-like layer.

Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients.

Objectives: Corneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation.

Fibrin and Marine-Derived Agaroses for the Generation of Human Bioartificial Tissues: An Ex Vivo and In Vivo Study.

Development of an ideal biomaterial for clinical use is one of the main objectives of current research in tissue engineering. Marine-origin polysaccharides, in particular agaroses, have been widely explored as scaffolds for tissue engineering. We previously developed a biomaterial based on a combination of agarose with fibrin, that was successfully translated to clinical practice.

Expression of Basement Membrane Molecules by Wharton Jelly Stem Cells (WJSC) in Full-Term Human Umbilical Cords, Cell Cultures and Microtissues.

Wharton's jelly stem cells (WJSC) from the human umbilical cord (UC) are one of the most promising mesenchymal stem cells (MSC) in tissue engineering (TE) and advanced therapies. The cell niche is a key element for both, MSC and fully differentiated tissues, to preserve their unique features. The basement membrane (BM) is an essential structure during embryonic development and in adult tissues.

Optical Behavior of Human Skin Substitutes: Absorbance in the 200-400 nm UV Range.

The most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200−280 nm), -B (280−315 nm), and -A (315−400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development.

Biological Effects of Maslinic Acid on Human Epithelial Cells Used in Tissue Engineering.

In the present work, we evaluated the potential of maslinic acid (MA) to improve currently available keratinocyte culture methods for use in skin tissue engineering. Results showed that MA can increase cell proliferation and WST-1 activity of human keratinocytes after 24, 48, and 72 h, especially at the concentration of 5 μg/ml, without affecting cell viability. This effect was associated to a significant increase of KI-67 protein expression and upregulation of several genes associated to cell proliferation (PCNA) and differentiation (cytokeratins, intercellular junctions and basement membrane related genes).

Histological Profiling of the Human Umbilical Cord: A Potential Alternative Cell Source in Tissue Engineering.

The embryonic development of the human umbilical cord (hUC) is complex, and different regions can be identified in this structure. The aim of this work is to characterize the hUC at in situ and ex vivo levels to stablish their potential use in vascular regeneration. Human umbilical cords were obtained and histologically prepared for in the situ analysis of four hUC regions (intervascular-IV, perivascular-PV, subaminoblastic-SAM, and Wharton's jelly-WH), and primary cell cultures of mesenchymal stem cells (hUC-MSC) isolated from each region were obtained.

Usefulness of a Nanostructured Fibrin-Agarose Bone Substitute in a Model of Severely Critical Mandible Bone Defect.

Critical defects of the mandibular bone are very difficult to manage with currently available materials and technology. In the present work, we generated acellular and cellular substitutes for human bone by tissue engineering using nanostructured fibrin-agarose biomaterials, with and without adipose-tissue-derived mesenchymal stem cells differentiated to the osteogenic lineage using inductive media. Then, these substitutes were evaluated in an immunodeficient animal model of severely critical mandibular bone damage in order to assess the potential of the bioartificial tissues to enable bone regeneration.

Improvement of Cell Culture Methods for the Successful Generation of Human Keratinocyte Primary Cell Cultures Using EGF-Loaded Nanostructured Lipid Carriers.

Human skin keratinocyte primary cultures can be established from skin biopsies with culture media containing epithelial growth factor (EGF). Although current methods are efficient, optimization is required to accelerate the procedure and obtain these cultures in less time. In the present study, we evaluated the effect of novel formulations based on EGF-loaded nanostructured lipid carriers (NLC).

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds.

Patients with severe limbal damage and limbal stem cell deficiency are a therapeutic challenge. We evaluated four decellularization protocols applied to the full-thickness and half-thickness porcine limbus, and we used two cell types to recellularize the decellularized limbi. The results demonstrated that all protocols achieved efficient decellularization.

Generation of a novel model of bioengineered human oral mucosa with increased vascularization potential.

Objective: The aim of this study was to generate novel models of bioartificial human oral mucosa with increased vascularization potential for future use as an advanced therapies medicinal product, by using different vascular and mesenchymal stem cell sources.

Background: Oral mucosa substitutes could contribute to the clinical treatment of complex diseases affecting the oral cavity. Although several models of artificial oral mucosa have been described, biointegration is a major issue that could be favored by the generation of novel substitutes with increased vascularization potential once grafted in vivo.

Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells.

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin-agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes.

Generation of a novel human dermal substitute functionalized with antibiotic-loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering.

Background: Treatment of patients affected by severe burns is challenging, especially due to the high risk of Pseudomonas infection. In the present work, we have generated a novel model of bioartificial human dermis substitute by tissue engineering to treat infected wounds using fibrin-agarose biomaterials functionalized with nanostructured lipid carriers (NLCs) loaded with two anti-Pseudomonas antibiotics: sodium colistimethate (SCM) and amikacin (AMK).

Results: Results show that the novel tissue-like substitutes have strong antibacterial effect on Pseudomonas cultures, directly proportional to the NLC concentration.

Erratum: Blanco-Elices, C. et al. In Vitro Generation of Novel Functionalized Biomaterials for Use in Oral and Dental Regenerative Medicine Applications. Running Title: Fibrin-Agarose Functionalized Scaffolds. 2020, , 1692.

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Long-Term Evaluation of Orthotypical and Heterotypical Bioengineered Human Corneas.

Purpose: Human cornea substitutes generated by tissue engineering currently require limbal stem cells for the generation of orthotypical epithelial cell cultures. We recently reported that bioengineered corneas can be fabricated from a heterotypical source obtained from Wharton's jelly in the human umbilical cord (HWJSC).

Methods: Here, we generated a partial thickness cornea model based on plastic compression nanostructured fibrin-agarose biomaterials with cornea epithelial cells on top, as an orthotypical model (HOC), or with HWJSC, as a heterotypical model (HHC), and determined their potential usefulness by implantation in an animal model.

In Vitro Generation of Novel Functionalized Biomaterials for Use in Oral and Dental Regenerative Medicine Applications. Running Title: Fibrin-Agarose Functionalized Scaffolds.

Recent advances in tissue engineering offer innovative clinical alternatives in dentistry and regenerative medicine. Tissue engineering combines human cells with compatible biomaterials to induce tissue regeneration. Shortening the fabrication time of biomaterials used in tissue engineering will contribute to treatment improvement, and biomaterial functionalization can be exploited to enhance scaffold properties.

Expanded Differentiation Capability of Human Wharton's Jelly Stem Cells Toward Pluripotency: A Systematic Review.

Human Wharton's jelly stem cells (HWJSC) can be efficiently isolated from the umbilical cord, and numerous reports have demonstrated that these cells can differentiate into several cell lineages. This fact, coupled with the high proliferation potential of HWJSC, makes them a promising source of stem cells for use in tissue engineering and regenerative medicine. However, their real potentiality has not been established to date.