Analysis of the role of perfusion, mechanical, and electrical stimulation in bioreactors for cardiac tissue engineering.

Since cardiovascular diseases (CVDs) are globally one of the leading causes of death, of which myocardial infarction (MI) can cause irreversible damage and decrease survivors' quality of life, novel therapeutics are needed. Current approaches such as organ transplantation do not fully restore cardiac function or are limited. As a valuable strategy, tissue engineering seeks to obtain constructs that resemble myocardial tissue, vessels, and heart valves using cells, biomaterials as scaffolds, biochemical and physical stimuli. The latter can be induced using a bioreactor mimicking the heart's physiological environment. An extensive review of bioreactors providing perfusion, mechanical and electrical stimulation, as well as the combination of them is provided. An analysis of the stimulations' mechanisms and modes that best suit cardiac construct culture is developed. Finally, we provide insights into bioreactor configuration and culture assessment properties that need to be elucidated for its clinical translation.

In vivo biocompatibility testing of nanoparticle-functionalized alginate-chitosan scaffolds for tissue engineering applications.

Background: There is a strong interest in designing new scaffolds for their potential application in tissue engineering and regenerative medicine. The incorporation of functionalization molecules can lead to the enhancement of scaffold properties, resulting in variations in scaffold compatibility. Therefore, the efficacy of the therapy could be compromised by the foreign body reaction triggered after implantation. Methods: In this study, the biocompatibilities of three scaffolds made from an alginate-chitosan combination and functionalized with gold nanoparticles (AuNp) and alginate-coated gold nanoparticles (AuNp + Alg) were evaluated in a subcutaneous implantation model in Wistar rats. Scaffolds and surrounding tissue were collected at 4-, 7- and 25-day postimplantation and processed for histological analysis and quantification of the expression of genes involved in angiogenesis, macrophage profile, and proinflammatory (IL-1ß and TNFα) and anti-inflammatory (IL-4 and IL-10) cytokines. Results: Histological analysis showed a characteristic foreign body response that resolved 25 days postimplantation. The intensity of the reaction assessed through capsule thickness was similar among groups. Functionalizing the device with AuNp and AuNp + Alg decreased the expression of markers associated with cell death by apoptosis and polymorphonuclear leukocyte recruitment, suggesting increased compatibility with the host tissue. Similarly, the formation of many foreign body giant cells was prevented. Finally, an increased detection of alpha smooth muscle actin was observed, showing the angiogenic properties of the elaborated scaffolds. Conclusion: Our results show that the proposed scaffolds have improved biocompatibility and exhibit promising potential as biomaterials for elaborating tissue engineering constructs.

Sodium Alginate/Chitosan Scaffolds for Cardiac Tissue Engineering: The Influence of Its Three-Dimensional Material Preparation and the Use of Gold Nanoparticles.

Natural biopolymer scaffolds and conductive nanomaterials have been widely used in cardiac tissue engineering; however, there are still challenges in the scaffold fabrication, which include enhancing nutrient delivery, biocompatibility and properties that favor the growth, maturation and functionality of the generated tissue for therapeutic application. In the present work, different scaffolds prepared with sodium alginate and chitosan (alginate/chitosan) were fabricated with and without the addition of metal nanoparticles and how their fabrication affects cardiomyocyte growth was evaluated. The scaffolds (hydrogels) were dried by freeze drying using calcium gluconate as a crosslinking agent, and two types of metal nanoparticles were incorporated, gold (AuNp) and gold plus sodium alginate (AuNp+Alg). A physicochemical characterization of the scaffolds was carried out by swelling, degradation, permeability and infrared spectroscopy studies. The results show that the scaffolds obtained were highly porous (>90%) and hydrophilic, with swelling percentages of around 3000% and permeability of the order of 1 × 10−8 m2. In addition, the scaffolds proposed favored adhesion and spheroid formation, with cardiac markers expression such as tropomyosin, troponin I and cardiac myosin. The incorporation of AuNp+Alg increased cardiac protein expression and cell proliferation, thus demonstrating their potential use in cardiac tissue engineering.

Effect of melatonin on electrical impedance and biomarkers of damage in a gastric ischemia/reperfusion model.

The damage to the gastrointestinal mucosa induced by ischemia/reperfusion (I/R) is closely related to high mortality in critically ill patients, which is attributable, in part, to the lack of an early method of diagnosis to show the degree of ischemia-induced injury in this type of patients. Electrical Impedance Spectroscopy (EIS) has been shown to be a tool to early diagnose gastric mucosal damage induced by ischemia. A therapeutic alternative to reduce this type of injury is melatonin (MT), which has gastroprotective effects in I/R models. In this work, the effect of treatment with MT on the electrical properties of gastric tissue, biomarkers of inflammatory (iNOS and COX-2), proliferation, and apoptotic process under I/R conditions in male Wistar rats was evaluated through EIS, histological and immunohistochemical analysis. Treatment with MT prevents gastric mucosa damage, causing a decrease in gastric impedance parameters related to the inflammatory process and cellular damage. This suggests that EIS could be used as a tool to diagnose and monitor the evolution of gastric mucosal injury, as well as in the recovery process in critically ill patients.

Sources, Characteristics, and Therapeutic Applications of Mesenchymal Cells in Tissue Engineering.

Tissue engineering (TE) is a therapeutic option within regenerative medicine that allows to mimic the original cell environment and functional organization of the cell types necessary for the recovery or regeneration of damaged tissue using cell sources, scaffolds, and bioreactors. Among the cell sources, the utilization of mesenchymal cells (MSCs) has gained great interest because these multipotent cells are capable of differentiating into diverse tissues, in addition to their self-renewal capacity to maintain their cell population, thus representing a therapeutic alternative for those diseases that can only be controlled with palliative treatments. This review aimed to summarize the state of the art of the main sources of MSCs as well as particular characteristics of each subtype and applications of MSCs in TE in seven different areas (neural, osseous, epithelial, cartilage, osteochondral, muscle, and cardiac) with a systemic revision of advances made in the last 10 years. It was observed that bone marrow-derived MSCs are the principal type of MSCs used in TE, and the most commonly employed techniques for MSCs characterization are immunodetection techniques. Moreover, the utilization of natural biomaterials is higher (41.96%) than that of synthetic biomaterials (18.75%) for the construction of the scaffolds in which cells are seeded. Further, this review shows alternatives of MSCs derived from other tissues and diverse strategies that can improve this area of regenerative medicine.