Biomimetic Strategies to Develop Bioactive Scaffolds for Myocardial Tissue Engineering

The aim of this paper is to provide an overview of the results of the research activity carried out in our laboratories, over the last 10 years, in relation to the development of strategies for the production of biomimetic and bioactive scaffolds for myocardial tissue engineering. Biomimetic and bioactive polymeric scaffolds for cardiac regeneration were designed and manufactured in our laboratories and their morphological, physicochemical, mechanical and biological properties were investigated by different techniques, such as scanning electron microscopy, infrared chemical imaging, swelling test, in vitro degradation assessment, dynamic mechanical analysis, in vitro and in vivo biological tests. Biomimetic scaffolds, able to favor tissue regeneration by mimicking nature, were engineered by different strategies, comprising: (i) the imitation of the composition and interactions among components of the natural extracellular matrix (ECM), by mixing of proteins and polysaccharides; (ii) the material surface modification, using both traditional and innovative techniques, such as molecular imprinting; (iii) the incorporation and release of specific active agents and (iv) the production of scaffolds with a microarchitecture similar to that of native ECM. All the developed strategies were found to be effective in creating materials able to influence cellular behavior and therefore to favor the process of new tissue formation. In particular, the approach based on the combination of different strategies aimed at creating a system capable of communicating with the cells and promoting specific cellular responses, as the ECM does, has appeared particularly promising, in view to favor the formation of a tissue equivalent to the cardiac one

Microfluidic Fabrication of Natural Polymer-Based Scaffolds for Tissue Engineering Applications: A Review

Natural polymers, thanks to their intrinsic biocompatibility and biomimicry, have been largely investigated as scaffold materials for tissue engineering applications. Traditional scaffold fabrication methods present several limitations, such as the use of organic solvents, the obtainment of a non-homogeneous structure, the variability in pore size and the lack of pore interconnectivity. These drawbacks can be overcome using innovative and more advanced production techniques based on the use of microfluidic platforms. Droplet microfluidics and microfluidic spinning techniques have recently found applications in the field of tissue engineering to produce microparticles and microfibers that can be used as scaffolds or as building blocks for three-dimensional structures. Compared to standard fabrication technologies, microfluidics-based ones offer several advantages, such as the possibility of obtaining particles and fibers with uniform dimensions. Thus, scaffolds with extremely precise geometry, pore distribution, pore interconnectivity and a uniform pores size can be obtained. Microfluidics can also represent a cheaper manufacturing technique. In this review, the microfluidic fabrication of microparticles, microfibers and three-dimensional scaffolds based on natural polymers will be illustrated. An overview of their applications in different tissue engineering fields will also be provided

Biomimetic and Bioactive Small Diameter Tubular Scaffolds for Vascular Tissue Engineering

The present work aimed at the production and characterization of small caliber biomimetic and bioactive tubular scaffolds, which are able to favor the endothelialization process, and therefore potentially be suitable for vascular tissue engineering. The tubular scaffolds were produced using a specially designed mold, starting from a gelatin/gellan/elastin (GGE) blend, selected to mimic the composition of the extracellular matrix of native blood vessels. GGE scaffolds were obtained through freeze-drying and subsequent cross-linking. To obtain systems capable of promoting endothelization, the scaffolds were functionalized using two different bioactive peptides, Gly-Arg-Gly-Asp-Ser-Pro (GRGSDP) and Arg-Glu-Asp-Val (REDV). A complete physicochemical, mechanical, functional, and biological characterization of the developed scaffolds was performed. GGE scaffolds showed a good porosity, which could promote cell infiltration and proliferation and a dense external surface, which could avoid bleeding. Moreover, developed scaffolds showed good hydrophilicity, an elastic behavior similar to natural vessels, suitability for sterilization by an ISO accepted treatment, and an adequate suture retention strength. In vitro cell culture tests showed no cytotoxic activity against 3T3 fibroblasts. The functionalization with the REDV peptide favored the adhesion and growth of endothelial cells, while GRGDSP-modified scaffolds represented a better substrate for fibroblasts

Chitosan-Based Macromolecular Biomaterials for the Regeneration of Chondroskeletal and Nerve Tissue

The use of materials, containing the biocompatible and bioresorbable biopolymer poly()-2-amino-2-deoxy--D-glucan, containing some N-acetyl-glucosamine units (chitosan, CHI) and/or its derivatives, to fabricate devices for the regeneration of bone, cartilage and nerve tissue, was reviewed. The CHI-containing devices, to be used for bone and cartilage regeneration and healing, were tested mainly for in vitro cell adhesion and proliferation and for insertion into animals; only the use of CHI in dental surgery has reached the clinical application. Regarding the nerve tissue, only a surgical repair of a 35 mm-long nerve defect in the median nerve of the right arm at elbow level with an artificial nerve graft, comprising an outer microporous conduit of CHI and internal oriented filaments of poly(glycolic acid), was reported. As a consequence, although many positive results have been obtained, much work must still be made, especially for the passage from the experimentation of the CHI-based devices, in vitro and in animals, to their clinical application

Ammonium thiosulphate assisted phytoextraction of mercury and arsenic in multi-polluted industrial soil

The possibility of using ammonium thiosulphate in assisted phytoextraction was evaluated on a greenhouse scale (mesocosm) for the simultaneous removal of mercury and arsenic from multi-polluted industrial soil. The addition of thiosulphate to the soil greatly promoted the uptake and translocation of both contaminants in the aerial parts of Brassica juncea and Lupinus albus. Thiosulphate showed great potential since it is a common fertilizer used to promote plant growth and is able to promote plant uptake of both Hg and As. Hg concentration in the aerial part of the plants reached 867 mg kg-1 in B. juncea and 114 mg kg-1 in L. albus. In the aerial parts, As concentration was about 9 mg kg-1 in B. juncea and 20 mg kg-1 in L. albus. This thus increases the applicability of phytoextraction in terms of cost and time especially if the remedial targets are based on bioavailable metal concentrations

Soil Remediation: Towards a Resilient and Adaptive Approach to Deal with the Ever-Changing Environmental Challenges

Pollution from numerous contaminants due to many anthropogenic activities affects soils quality. Industrialized countries have many contaminated sites; their remediation is a priority in environmental legislation. The aim of this overview is to consider the evolution of soil remediation from consolidated invasive technologies to environmentally friendly green strategies. The selection of technology is no longer exclusively based on eliminating the source of pollution but aims at remediation, which includes the recovery of soil quality. \u201cGreen remediation\u201d appears to be the key to addressing the issue of remediation of contaminated sites as it focuses on environmental quality, including the preservation of the environment. Further developments in green remediation reflect the aim of promoting clean-up strategies that also address the effects of climate change. Sustainable and resilient remediation faces the environmental challenge of achieving targets while reducing the environmental damage caused by clean-up interventions and must involve an awareness that social systems and environmental systems are closely connected

Mending a broken heart by biomimetic 3D printed natural biomaterial-based cardiac patches: a review

: Myocardial infarction is one of the major causes of mortality as well as morbidity around the world. Currently available treatment options face a number of drawbacks, hence cardiac tissue engineering, which aims to bioengineer functional cardiac tissue, for application in tissue repair, patient specific drug screening and disease modeling, is being explored as a viable alternative. To achieve this, an appropriate combination of cells, biomimetic scaffolds mimicking the structure and function of the native tissue, and signals, is necessary. Among scaffold fabrication techniques, three-dimensional printing, which is an additive manufacturing technique that enables to translate computer-aided designs into 3D objects, has emerged as a promising technique to develop cardiac patches with a highly defined architecture. As a further step toward the replication of complex tissues, such as cardiac tissue, more recently 3D bioprinting has emerged as a cutting-edge technology to print not only biomaterials, but also multiple cell types simultaneously. In terms of bioinks, biomaterials isolated from natural sources are advantageous, as they can provide exceptional biocompatibility and bioactivity, thus promoting desired cell responses. An ideal biomimetic cardiac patch should incorporate additional functional properties, which can be achieved by means of appropriate functionalization strategies. These are essential to replicate the native tissue, such as the release of biochemical signals, immunomodulatory properties, conductivity, enhanced vascularization and shape memory effects. The aim of the review is to present an overview of the current state of the art regarding the development of biomimetic 3D printed natural biomaterial-based cardiac patches, describing the 3D printing fabrication methods, the natural-biomaterial based bioinks, the functionalization strategies, as well as the in vitro and in vivo applications

IGF-1 loaded injectable microspheres for potential repair of the infarcted myocardium

The use of injectable scaffolds to repair the infarcted heart is receiving great interest. Thermosensitive polymers, in situ polymerization, in situ cross-linking, and self-assembling peptides are the most investigated approaches to obtain injectability. Aim of the present work was the preparation and characterization of a novel bioactive scaffold, in form of injectable microspheres, for cardiac repair. Gellan/gelatin microspheres were prepared by a water-in-oil emulsion and loaded by adsorption with Insulin-like growth factor 1 to promote tissue regeneration. Obtained microspheres underwent morphological, physicochemical and biological characterization, including cell culture tests in static and dynamic conditions and in vivo tests. Morphological analysis of the microspheres showed a spherical shape, a microporous surface and an average diameter of 66 ± 17mm (under dry conditions) and 123 ± 24 mm (under wet conditions). Chemical Imaging analysis pointed out a homogeneous distribution of gellan, gelatin and Insulin-like growth factor-1 within the microsphere matrix. In vitro cell culture tests showed that the microspheres promoted rat cardiac progenitor cells adhesion, and cluster formation. After dynamic suspension culture within an impeller-free bioreactor, cells still adhered to microspheres, spreading their cytoplasm over microsphere surface. Intramyocardial administration of microspheres in a cryoinjury rat model attenuated chamber dilatation, myocardial damage and fibrosis and improved cell homing. Overall, the findings of this study confirm that the produced microspheres display morphological, physicochemical, functional and biological properties potentially adequate for future applications as injectable scaffold for cardiac tissue engineering