An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function

Direct-Write Deposition of Thermogels

The use of biocompatible hydrogels has widely extended the potential of additive manufacturing (AM) in the biomedical field leading to the production of 3D tissue and organ analogs for in vitro and in vivo studies. In this work, the direct-write deposition of thermosensitive hydrogels is described as a facile route to obtain 3D cell-laden constructs with controlled 3D structure and stable behavior under physiological conditions

Wound dressing products: A translational investigation from the bench to the market

Chronic skin wounds affect more than 40 million patients globally and represent a severe growing burden for the healthcare systems, with annual costs expected to exceed $15 billions by 2022. To satisfy the huge demand for effective wound care products, different types of wound dressings have been introduced on the market during the last decades. Based on “the moist wound healing theory” postulated by Prof Winter in 1962, bandages were initially designed to recreate the optimal wound environment to favor the healing process. Then, thanks to the advancements achieved in biomaterial design and processing, biotechnology, imaging and electronic fields, great effort has been devoted to the development of formulations able to actively participate to tissue healing. Indeed, both the literature and the market report the design of medicated wound dressings, i.e., wound care products releasing anti-microbial agents, anti-inflammatory drugs, or bioactive molecules. In this scenario, this review aims at critically describing the currently available wound care products, highlighting their proved effectiveness in wound management. Moreover, an overview of the main strategies exploited to design personalized wound dressings has been reported. Lastly, concerns on regulatory affairs and practical issues limiting the clinical translation of advanced research platforms have also been discussed

MicroRNA-Mediated Direct Reprogramming of Human Adult Fibroblasts Toward Cardiac Phenotype

open6Modulation of microRNA expression holds the promise to achieve direct reprogramming of fibroblasts into cardiomyocyte-like cells as a new strategy for myocardial regeneration after ischemic heart disease. Previous reports have shown that murine fibroblasts can be directly reprogrammed into induced cardiomyocytes (iCMs) by transient transfection with four microRNA mimics (miR-1, 133, 208, and 499, termed "miRcombo"). Hence, study on the effect of miRcombo transfection on adult human cardiac fibroblasts (AHCFs) deserves attention in the perspective of a future clinical translation of the approach. In this brief report, we studied for the first time whether miRcombo transient transfection of AHCFs by non-viral vectors might trigger direct reprogramming of AHCFs into cardiomyocyte-like cells. Initially, efficient miRNA delivery to cells was demonstrated through the use of a commercially available transfection agent (DharmaFECT1). Transient transfection of AHCFs with miRcombo was found to upregulate early cardiac transcription factors after 7 days post-transfection and cardiomyocyte specific marker cTnT after 15 days post-transfection, and to downregulate the expression of fibroblast markers at 15 days post-transfection. The percentage of cTnT-positive cells after 15 days from miRcombo transfection was ∼11%, as evaluated by flow cytometry. Furthermore, a relevant percentage of miRcombo-transfected AHCFs (∼38%) displayed spontaneous calcium transients at 30 days post-transfection. Results evidenced the role of miRcombo transfection on triggering the trans differentiation of AHCFs into iCMs. Although further investigations are needed to achieve iCM maturation, early findings from this study pave the way toward new advanced therapies for human cardiac regeneration.openPaoletti C; Divieto C; Tarricone G; Di Meglio F; Nurzynska D; Chiono VPaoletti, C; Divieto, C; Tarricone, G; Di Meglio, F; Nurzynska, D; Chiono,

MicroRNA delivery through nanoparticles

MicroRNAs (miRNAs) are attracting a growing interest in the scientific community due to their central role in the etiology of major diseases. On the other hand, nanoparticle carriers offer unprecedented opportunities for cell specific controlled delivery of miRNAs for therapeutic purposes. This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration. A fresh perspective is presented on the design and characterization of nanocarriers to accelerate translation from basic research to clinical application of miRNA-nanoparticles. Main challenges in the engineering of miRNA-loaded nanoparticles are discussed, and key application examples are highlighted to underline their therapeutic potential for effective and personalized medicine

Influence of Drug-Carrier Polymers on Alpha-Synucleinopathies: A Neglected Aspect in New Therapies Development.

Current therapeutic strategies to treat neurodegenerative diseases, such as alpha-synucleinopathies, aim at enhancing the amount of drug reaching the brain. Methods proposed, such as intranasal administration, should be able to bypass the blood brain barrier (BBB) and even when directly intracerebrally injected they could require a carrier to enhance local release of drugs. We have investigated the effect of a model synthetic hydrogel to be used as drug carrier on the amount of alpha-synuclein aggregates in cells in culture. The results indicated that alpha-synuclein aggregation was affected by the synthetic polymer, suggesting the need for testing the effect of any used material on the pathological process before its application as drug carrier.Peer Reviewe