Biomaterials Tailoring at the Nanoscale for Tissue Engineering and Advanced Therapies

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 37393

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Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10129 Torino, Italy
Interests: biomedical and biodegradable polymers; polyurethanes; surface functionalisation; tissue engineering; polymeric nanoparticles for nanomedicine; tissue and organ models; additive manufacturing and bioprinting
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Special Issue Information

Dear Colleagues,

The control of matter at the nanoscale has demonstrated an enormous potential in the development of engineered devices in several applications such as energy, paintings and coatings, electronics, and textiles. In the medical field, the design of materials and structures with nanometric precision has demonstrated its enormous potential in controlling cellular processes such as adhesion, proliferation, and differentiation, while nanosized carriers have shown enhanced efficacy and precision in delivering therapeutic or diagnostic payloads to specific living environments.

After an exciting decade of research in the fascinating, supradisciplinary field of bionanotechnology, times are now mature for transferring the results of this research to a higher technology-readiness level and to evaluate their real potential to be translated from the bench to the bedside. On the other hand, further research is needed to understand the mechanisms (including topographical, mechanical, and (bio)chemical cues) underlying the interaction of living environments with nanostructured materials and surfaces. In this scenario, the present topic calls for papers describing breakthrough research in the field of bionanotechnology and its exploitation in tissue engineering/regenerative medicine, drug and gene delivery, cell therapy, and organ models. Attention will be given both to the bottom-up design of nanobiomaterials through modern chemical synthesis (e.g., click chemistry) or self-assembly, and to the top-down realization of nanostructures through nanofabrication techniques (e.g., two-photon lithography). Papers dedicated to analytical methods to characterize nanomaterials and nanostructures for biomedical application are also warmly welcomed.

Prof. Dr. Gianluca Ciardelli
Dr. Monica Boffito
Guest Editors

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Published Papers (12 papers)

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Editorial

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4 pages, 198 KiB  
Editorial
Biomaterials Tailoring at the Nanoscale for Tissue Engineering and Advanced Therapies
by Monica Boffito and Gianluca Ciardelli
Nanomaterials 2021, 11(5), 1221; https://doi.org/10.3390/nano11051221 - 06 May 2021
Viewed by 1549
Abstract
The definition of the term “biomaterial” dates back to 1991, during the 2nd Consensus Conference on the Definitions in Biomaterials organized by the European Society of Biomaterials in Chester (UK) [...] Full article

Research

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23 pages, 7208 KiB  
Article
Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
by Sonia Fiorilli, Mattia Pagani, Elena Boggio, Casimiro Luca Gigliotti, Chiara Dianzani, Rémy Gauthier, Carlotta Pontremoli, Giorgia Montalbano, Umberto Dianzani and Chiara Vitale-Brovarone
Nanomaterials 2021, 11(2), 321; https://doi.org/10.3390/nano11020321 - 27 Jan 2021
Cited by 17 | Viewed by 2723
Abstract
Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic [...] Read more.
Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic effects (i.e., pro-osteogenic, anti-clastogenic) can allow the design of effective medical solutions. With this aim, in this work, strontium-containing mesoporous bioactive glasses (MBGs) were bio-functionalized with ICOS-Fc, a molecule able to reversibly inhibit osteoclast activity by binding the respective ligand (ICOS-L) and to induce a decrease of bone resorption activity. N2 adsorption analysis and FT-IR spectroscopy were used to assess the successful grafting of ICOS-Fc on the surface of Sr-containing MBGs, which were also proved to retain the peculiar ability to release osteogenic strontium ions and an excellent bioactivity after functionalization. An ELISA-like assay allowed to confirm that grafted ICOS-Fc molecules were able to bind ICOS-L (the ICOS binding ligand) and to investigate the stability of the amide binding to hydrolysis in aqueous environment up to 21 days. In analogy to the free form of the molecule, the inhibitory effect of grafted ICOS-Fc on cell migratory activity was demonstrated by using ICOSL positive cell lines and the ability to inhibit osteoclast differentiation and function was confirmed by monitoring the differentiation of monocyte-derived osteoclasts (MDOCs), which revealed a strong inhibitory effect, also proven by the downregulation of osteoclast differentiation genes. The obtained results showed that the combination of ICOS-Fc with the intrinsic properties of Sr-containing MBGs represents a very promising approach to design personalized solutions for patients affected by compromised bone remodeling (i.e., osteoporosis fractures). Full article
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12 pages, 2668 KiB  
Article
Biodegradable Hydrogels Loaded with Magnetically Responsive Microspheres as 2D and 3D Scaffolds
by Estela O. Carvalho, Clarisse Ribeiro, Daniela M. Correia, Gabriela Botelho and Senentxu Lanceros-Mendez
Nanomaterials 2020, 10(12), 2421; https://doi.org/10.3390/nano10122421 - 03 Dec 2020
Cited by 10 | Viewed by 2560
Abstract
Scaffolds play an essential role in the success of tissue engineering approaches. Their intrinsic properties are known to influence cellular processes such as adhesion, proliferation and differentiation. Hydrogel-based matrices are attractive scaffolds due to their high-water content resembling the native extracellular matrix. In [...] Read more.
Scaffolds play an essential role in the success of tissue engineering approaches. Their intrinsic properties are known to influence cellular processes such as adhesion, proliferation and differentiation. Hydrogel-based matrices are attractive scaffolds due to their high-water content resembling the native extracellular matrix. In addition, polymer-based magnetoelectric materials have demonstrated suitable bioactivity, allowing to provide magnetically and mechanically activated biophysical electrical stimuli capable of improving cellular processes. The present work reports on a responsive scaffold based on poly (L-lactic acid) (PLLA) microspheres and magnetic microsphere nanocomposites composed of PLLA and magnetostrictive cobalt ferrites (CoFe2O4), combined with a hydrogel matrix, which mimics the tissue’s hydrated environment and acts as a support matrix. For cell proliferation evaluation, two different cell culture conditions (2D and 3D matrices) and two different strategies, static and dynamic culture, were applied in order to evaluate the influence of extracellular matrix-like confinement and the magnetoelectric/magneto-mechanical effect on cellular behavior. MC3T3-E1 proliferation rate is increased under dynamic conditions, indicating the potential use of hydrogel matrices with remotely stimulated magnetostrictive biomaterials for bone tissue engineering. Full article
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24 pages, 5214 KiB  
Article
Embedding Ordered Mesoporous Carbons into Thermosensitive Hydrogels: A Cutting-Edge Strategy to Vehiculate a Cargo and Control Its Release Profile
by Monica Boffito, Rossella Laurano, Dimitra Giasafaki, Theodore Steriotis, Athanasios Papadopoulos, Chiara Tonda-Turo, Claudio Cassino, Georgia Charalambopoulou and Gianluca Ciardelli
Nanomaterials 2020, 10(11), 2165; https://doi.org/10.3390/nano10112165 - 29 Oct 2020
Cited by 8 | Viewed by 1968
Abstract
The high drug loading capacity, cytocompatibility and easy functionalization of ordered mesoporous carbons (OMCs) make them attractive nanocarriers to treat several pathologies. OMCs’ efficiency could be further increased by embedding them into a hydrogel phase for an in loco prolonged drug release. In [...] Read more.
The high drug loading capacity, cytocompatibility and easy functionalization of ordered mesoporous carbons (OMCs) make them attractive nanocarriers to treat several pathologies. OMCs’ efficiency could be further increased by embedding them into a hydrogel phase for an in loco prolonged drug release. In this work, OMCs were embedded into injectable thermosensitive hydrogels. In detail, rod-like (diameter ca. 250 nm, length ca. 700 nm) and spherical (diameter approximately 120 nm) OMCs were synthesized by nanocasting selected templates and loaded with ibuprofen through a melt infiltration method to achieve complete filling of their pores (100% loading yield). In parallel, an amphiphilic Poloxamer® 407-based poly(ether urethane) was synthesized (Mn¯ 72 kDa) and solubilized at 15 and 20% w/v concentration in saline solution to design thermosensitive hydrogels. OMC incorporation into the hydrogels (10 mg/mL concentration) did not negatively affect their gelation potential. Hybrid systems successfully released ibuprofen at a slower rate compared to control gels (gels embedding ibuprofen as such), but with no significant differences between rod-like and spherical OMC-loaded gels. OMCs can thus work as effective drug reservoirs that progressively release their payload over time and also upon encapsulation in a hydrogel phase, thus opening the way to their application to treat many different pathological states (e.g., as topical medications). Full article
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11 pages, 10821 KiB  
Article
Bilayered Fibrin-Based Electrospun-Sprayed Scaffold Loaded with Platelet Lysate Enhances Wound Healing in a Diabetic Mouse Model
by Paola Losi, Tamer Al Kayal, Marianna Buscemi, Ilenia Foffa, Aida Cavallo and Giorgio Soldani
Nanomaterials 2020, 10(11), 2128; https://doi.org/10.3390/nano10112128 - 27 Oct 2020
Cited by 20 | Viewed by 2383
Abstract
The present study examined the effects of a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate by a combination of electrospinning and spray, phase-inversion method for wound healing. In particular, the poly(ether)urethane layer was obtained using by a spray phase-inversion method and the fibrin [...] Read more.
The present study examined the effects of a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate by a combination of electrospinning and spray, phase-inversion method for wound healing. In particular, the poly(ether)urethane layer was obtained using by a spray phase-inversion method and the fibrin fibers network were loaded with platelet lysate by electrospinning. The kinetics release and the bioactivity of growth factors released from platelet lysate-scaffold were investigated by ELISA and cell proliferation test using mouse fibroblasts, respectively. The in-vitro experiments demonstrated that a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate provides a sustained release of bioactive platelet-derived growth factors. The effect of a bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate on wound healing in diabetic mouse (db/db) was also investigated. The application of the scaffold on full-thickness skin wounds significantly accelerated wound closure at day 14 post-surgery when compared to scaffold without platelet lysates or commercially available polyurethane film, and at the same level of growth factor-loaded scaffold. Histological analysis demonstrated an increased re-epithelialization and collagen deposition in platelet lysate and growth factor loaded scaffolds. The ability of bilayered fibrin/poly(ether)urethane scaffold loaded with platelet lysate to promote in-vivo wound healing suggests its usefulness in clinical treatment of diabetic ulcers. Full article
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14 pages, 2408 KiB  
Article
Icariin-Functionalized Nanodiamonds to Enhance Osteogenic Capacity In Vitro
by Somang Choi, Sung Hyun Noh, Chae Ouk Lim, Hak-Jun Kim, Han-Saem Jo, Ji Seon Min, Kyeongsoon Park and Sung Eun Kim
Nanomaterials 2020, 10(10), 2071; https://doi.org/10.3390/nano10102071 - 20 Oct 2020
Cited by 13 | Viewed by 2195
Abstract
Nanodiamonds (NDs) have been used as drug delivery vehicles due to their low toxicity and biocompatibility. Recently, it has been reported that NDs have also osteogenic differentiation capacity. However, their capacity using NDs alone is not enough. To significantly improve their osteogenic activity, [...] Read more.
Nanodiamonds (NDs) have been used as drug delivery vehicles due to their low toxicity and biocompatibility. Recently, it has been reported that NDs have also osteogenic differentiation capacity. However, their capacity using NDs alone is not enough. To significantly improve their osteogenic activity, we developed icariin (ICA)-functionalized NDs (ICA-NDs) and evaluated whether ICA-NDs enhance their in vitro osteogenic capacity. Unmodified NDs and ICA-NDs showed nanosized particles that were spherical in shape. The ICA-NDs achieved a prolonged ICA release for up to 4 weeks. The osteogenic capacities of NDs, ICA (10 μg)-NDs, and ICA (50 μg)-NDs were demonstrated by alkaline phosphatase (ALP) activity; calcium content; and mRNA gene levels of osteogenic-related markers, including ALP, runt-related transcript factor 2 (RUNX2), collagen type I alpha 1 (COL1A1), and osteopontin (OPN). In vitro cell studies revealed that ICA (50 μg)-ND-treated MC3T3-E1 cells greatly increased osteogenic markers, including ALP, calcium content, and mRNA gene levels of osteogenic-related markers, including ALP, RUNX2, COL1A1, and OPN compared to ICA (10 μg)-NDs or ND-treated cells. These our data suggest that ICA-NDs can promote osteogenic capacity. Full article
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21 pages, 11908 KiB  
Article
Synergistic Effect of Chitosan and Selenium Nanoparticles on Biodegradation and Antibacterial Properties of Collagenous Scaffolds Designed for Infected Burn Wounds
by Jana Dorazilová, Johana Muchová, Kristýna Šmerková, Silvia Kočiová, Pavel Diviš, Pavel Kopel, Radek Veselý, Veronika Pavliňáková, Vojtěch Adam and Lucy Vojtová
Nanomaterials 2020, 10(10), 1971; https://doi.org/10.3390/nano10101971 - 05 Oct 2020
Cited by 34 | Viewed by 4132
Abstract
A highly porous scaffold is a desirable outcome in the field of tissue engineering. The porous structure mediates water-retaining properties that ensure good nutrient transportation as well as creates a suitable environment for cells. In this study, porous antibacterial collagenous scaffolds containing chitosan [...] Read more.
A highly porous scaffold is a desirable outcome in the field of tissue engineering. The porous structure mediates water-retaining properties that ensure good nutrient transportation as well as creates a suitable environment for cells. In this study, porous antibacterial collagenous scaffolds containing chitosan and selenium nanoparticles (SeNPs) as antibacterial agents were studied. The addition of antibacterial agents increased the application potential of the material for infected and chronic wounds. The morphology, swelling, biodegradation, and antibacterial activity of collagen-based scaffolds were characterized systematically to investigate the overall impact of the antibacterial additives. The additives visibly influenced the morphology, water-retaining properties as well as the stability of the materials in the presence of collagenase enzymes. Even at concentrations as low as 5 ppm of SeNPs, modified polymeric scaffolds showed considerable inhibition activity towards Gram-positive bacterial strains such as Staphylococcus aureus and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis in a dose-dependent manner. Full article
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13 pages, 1517 KiB  
Article
Development of Magnetic Torque Stimulation (MTS) Utilizing Rotating Uniform Magnetic Field for Mechanical Activation of Cardiac Cells
by Myeongjin Song, Jongseong Kim, Hyundo Shin, Yekwang Kim, Hwanseok Jang, Yongdoo Park and Seung-Jong Kim
Nanomaterials 2020, 10(9), 1684; https://doi.org/10.3390/nano10091684 - 27 Aug 2020
Cited by 6 | Viewed by 3745
Abstract
Regulation of cell signaling through physical stimulation is an emerging topic in biomedicine. Background: While recent advances in biophysical technologies show capabilities for spatiotemporal stimulation, interfacing those tools with biological systems for intact signal transfer and noncontact stimulation remains challenging. Here, we describe [...] Read more.
Regulation of cell signaling through physical stimulation is an emerging topic in biomedicine. Background: While recent advances in biophysical technologies show capabilities for spatiotemporal stimulation, interfacing those tools with biological systems for intact signal transfer and noncontact stimulation remains challenging. Here, we describe the use of a magnetic torque stimulation (MTS) system combined with engineered magnetic particles to apply forces on the surface of individual cells. MTS utilizes an externally rotating magnetic field to induce a spin on magnetic particles and generate torsional force to stimulate mechanotransduction pathways in two types of human heart cells—cardiomyocytes and cardiac fibroblasts. Methods: The MTS system operates in a noncontact mode with two magnets separated (60 mm) from each other and generates a torque of up to 15 pN µm across the entire area of a 35-mm cell culture dish. The MTS system can mechanically stimulate both types of human heart cells, inducing maturation and hypertrophy. Results: Our findings show that application of the MTS system under hypoxic conditions induces not only nuclear localization of mechanoresponsive YAP proteins in human heart cells but also overexpression of hypertrophy markers, including β-myosin heavy chain (βMHC), cardiotrophin-1 (CT-1), microRNA-21 (miR-21), and transforming growth factor beta-1 (TGFβ-1). Conclusions: These results have important implications for the applicability of the MTS system to diverse in vitro studies that require remote and noninvasive mechanical regulation. Full article
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18 pages, 4244 KiB  
Article
A Peptide-Based Nanocarrier for an Enhanced Delivery and Targeting of Flurbiprofen into the Brain for the Treatment of Alzheimer’s Disease: An In Vitro Study
by Shafq Al-azzawi, Dhafir Masheta, Anna Guildford, Gary Phillips and Matteo Santin
Nanomaterials 2020, 10(8), 1590; https://doi.org/10.3390/nano10081590 - 13 Aug 2020
Cited by 10 | Viewed by 2865
Abstract
Alzheimer’s disease (AD) is an age-related disease caused by abnormal accumulation of amyloid-β in the brain leading to progressive tissue degeneration. Flurbiprofen (FP), a drug used to mitigate the disease progression, has low efficacy due to its limited permeability across the blood–brain barrier [...] Read more.
Alzheimer’s disease (AD) is an age-related disease caused by abnormal accumulation of amyloid-β in the brain leading to progressive tissue degeneration. Flurbiprofen (FP), a drug used to mitigate the disease progression, has low efficacy due to its limited permeability across the blood–brain barrier (BBB). In a previous work, FP was coupled at the uppermost branching of an ε-lysine-based branched carrier, its root presenting a phenylalanine moiety able to increase the hydrophobicity of the complex and enhance the transport across the BBB by adsorptive-mediated transcytosis (AMT). The present study explores a different molecular design of the FP-peptide delivery system, whereby its root presents an ApoE-mimicking peptide, a targeting ligand that could enhance transport across the BBB by receptor-mediated transcytosis (RMT). The functionalised complex was synthesised using a solid-phase peptide synthesis and characterised by mass spectrometry and FTIR. Cytotoxicity and permeability of this complex across an in vitro BBB model were analysed. Moreover, its activity and degradation to release the drug were investigated. The results revealed successful synthesis and grafting of FP molecules at the uppermost molecular branches of the lysine terminal without observed cytotoxicity. When covalently linked to the nanocarrier, FP was still active on target cells, albeit with a reduced activity, and was released as a free drug upon hydrolysis in a lysosome-mimicking medium. Noticeably, this work shows the high efficiency of RMT-driven FP delivery over delivery systems relying on AMT. Full article
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Review

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33 pages, 2803 KiB  
Review
Extracellular Vesicle-Based Therapeutics for Heart Repair
by Laura Saludas, Cláudia C. Oliveira, Carmen Roncal, Adrián Ruiz-Villalba, Felipe Prósper, Elisa Garbayo and María J. Blanco-Prieto
Nanomaterials 2021, 11(3), 570; https://doi.org/10.3390/nano11030570 - 25 Feb 2021
Cited by 26 | Viewed by 3026
Abstract
Extracellular vesicles (EVs) are constituted by a group of heterogeneous membrane vesicles secreted by most cell types that play a crucial role in cell–cell communication. In recent years, EVs have been postulated as a relevant novel therapeutic option for cardiovascular diseases, including myocardial [...] Read more.
Extracellular vesicles (EVs) are constituted by a group of heterogeneous membrane vesicles secreted by most cell types that play a crucial role in cell–cell communication. In recent years, EVs have been postulated as a relevant novel therapeutic option for cardiovascular diseases, including myocardial infarction (MI), partially outperforming cell therapy. EVs may present several desirable features, such as no tumorigenicity, low immunogenic potential, high stability, and fine cardiac reparative efficacy. Furthermore, the natural origin of EVs makes them exceptional vehicles for drug delivery. EVs may overcome many of the limitations associated with current drug delivery systems (DDS), as they can travel long distances in body fluids, cross biological barriers, and deliver their cargo to recipient cells, among others. Here, we provide an overview of the most recent discoveries regarding the therapeutic potential of EVs for addressing cardiac damage after MI. In addition, we review the use of bioengineered EVs for targeted cardiac delivery and present some recent advances for exploiting EVs as DDS. Finally, we also discuss some of the most crucial aspects that should be addressed before a widespread translation to the clinical arena. Full article
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19 pages, 1947 KiB  
Review
Biomimetic vs. Direct Approach to Deposit Hydroxyapatite on the Surface of Low Melting Point Polymers for Tissue Engineering
by Andri K. Riau, Subbu S. Venkatraman and Jodhbir S. Mehta
Nanomaterials 2020, 10(11), 2162; https://doi.org/10.3390/nano10112162 - 29 Oct 2020
Cited by 11 | Viewed by 2947
Abstract
Polymers are widely used in many applications in the field of biomedical engineering. Among eclectic selections of polymers, those with low melting temperature (Tm < 200 °C), such as poly(methyl methacrylate), poly(lactic-co-glycolic acid), or polyethylene, are often used in bone, dental, maxillofacial, [...] Read more.
Polymers are widely used in many applications in the field of biomedical engineering. Among eclectic selections of polymers, those with low melting temperature (Tm < 200 °C), such as poly(methyl methacrylate), poly(lactic-co-glycolic acid), or polyethylene, are often used in bone, dental, maxillofacial, and corneal tissue engineering as substrates or scaffolds. These polymers, however, are bioinert, have a lack of reactive surface functional groups, and have poor wettability, affecting their ability to promote cellular functions and biointegration with the surrounding tissue. Improving the biointegration can be achieved by depositing hydroxyapatite (HAp) on the polymeric substrates. Conventional thermal spray and vapor phase coating, including the Food and Drug Administration (FDA)-approved plasma spray technique, is not suitable for application on the low Tm polymers due to the high processing temperature, reaching more than 1000 °C. Two non-thermal HAp coating approaches have been described in the literature, namely, the biomimetic deposition and direct nanoparticle immobilization techniques. In the current review, we elaborate on the unique features of each technique, followed by discussing the advantages and disadvantages of each technique to help readers decide on which method is more suitable for their intended applications. Finally, the future perspectives of the non-thermal HAp coating are given in the conclusion. Full article
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32 pages, 7329 KiB  
Review
Melanin and Melanin-Like Hybrid Materials in Regenerative Medicine
by Chiara Cavallini, Giuseppe Vitiello, Barbara Adinolfi, Brigida Silvestri, Paolo Armanetti, Paola Manini, Alessandro Pezzella, Marco d’Ischia, Giuseppina Luciani and Luca Menichetti
Nanomaterials 2020, 10(8), 1518; https://doi.org/10.3390/nano10081518 - 03 Aug 2020
Cited by 43 | Viewed by 6452
Abstract
Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many [...] Read more.
Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many biological functions ensuring homeostasis. Due to their broad-spectrum light absorption, radical scavenging, electric conductivity, and paramagnetic behavior, eumelanins are widely studied in the biomedical field. The continuing advancements in the development of biomimetic design strategies offer novel opportunities toward specifically engineered multifunctional biomaterials for regenerative medicine. Melanin and melanin-like coatings have been shown to increase cell attachment and proliferation on different substrates and to promote and ameliorate skin, bone, and nerve defect healing in several in vivo models. Herein, the state of the art and future perspectives of melanins as promising bioinspired platforms for natural regeneration processes are highlighted and discussed. Full article
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