Functionalized Polymeric Biomaterials: Design and Applications

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Guest Editor
Neuro-Computing and Neuro-Robotics Research Group, Complutense University of Madrid, Madrid, Spain
Interests: silk; biomaterials; neural plasticity; neural interfaces
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Guest Editor
Escuela Técnica Superior de Ingenieros de Caminos Canales y Puertos, Madrid, Spain
Interests: silk; biomaterials; functionalization; cell therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The functionalization of biomaterials offers a promising strategy for improving the response of the organism to the implant. This approach is especially convenient when combined with polymeric materials that may be used in applications such as scaffolds for tissue regeneration and repair, vehicles for drugs and/or stem cell encapsulation and delivery (precision and personalized medicine), artificial tendons and ligaments development, as structural elements of artificial extracellular matrices, etc. The synthesis of these functionalized biomaterials must consider the employment of biocompatible molecules, such as silk or collagen, that, in addition, should be produced in different formats (e.g., films, fibers, sponges, gels)  by using appropriate processing techniques. Since functionalization requires the introduction at the surface of the material of reactive groups, it is possible to consider different crosslinking chemistries compatible with each material and format. The need to bind the reactive moieties to the material also offers a nice opportunity to employ Genetic Engineering techniques to enhance the properties exhibited by the natural material. In this context, this Special Issue aims to provide an updated view of the main promises and challenges of using this type of material for biomedical applications.

Prof. Dr. Fivos Panetsos
Prof. Dr. Jose Perez-Rigueiro
Guest Editors

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Keywords

  • silk
  • functionalization
  • tissue engineering
  • regenerative medicine
  • stem cells
  • crosslinker

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Related Special Issue

Published Papers (7 papers)

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Research

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23 pages, 6681 KiB  
Article
Polyacrylate–Cholesterol Amphiphilic Derivative: Formulation Development and Scale-up for Health Care Applications
by Marco Viola, Claudia Migliorini, Fabio Ziarelli, Stéphane Viel, Claudia Cencetti, Daniel Di Risola, Luciana Mosca, Laura Masuelli, Pietro Matricardi and Chiara Di Meo
J. Funct. Biomater. 2023, 14(9), 482; https://doi.org/10.3390/jfb14090482 - 20 Sep 2023
Cited by 1 | Viewed by 1778
Abstract
The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable [...] Read more.
The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release. PAAbCH also formed polyelectrolyte hydrogel complexes with chitosan, both at the macro- and nano-scale. The results demonstrate that this polymer has promising potential as an innovative excipient, acting as a solubility enhancer, viscosity enhancer, and emulsifying agent with an easy scale-up transfer process. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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11 pages, 2988 KiB  
Article
Production of Feline Universal Erythrocytes with Methoxy Polyethylene Glycol
by Hyung Kyu Kim, Dan Bi Ahn, Han Byeol Jang, Jing Ma, Juping Xing, Joo Won Yoon, Kyung Hee Lee, Dong Min Lee, Chang Hyun Kim and Hee Young Kim
J. Funct. Biomater. 2023, 14(9), 476; https://doi.org/10.3390/jfb14090476 - 18 Sep 2023
Viewed by 1708
Abstract
Blood group mismatch in veterinary medicine is a significant problem in blood transfusion, sometimes leading to severe transfusion reactions and even patient death. Blood groups vary from species to species and there are three known blood groups in cats: A, B and AB. [...] Read more.
Blood group mismatch in veterinary medicine is a significant problem in blood transfusion, sometimes leading to severe transfusion reactions and even patient death. Blood groups vary from species to species and there are three known blood groups in cats: A, B and AB. While A-type cats are most common, there is a shortage of feline B-type blood groups in cats. By using methoxy polyethylene glycol (mPEG) to protect antigenic epitopes on red blood cells (RBCs), we aimed to find the optimal conditions for the production of feline universal RBCs. The surfaces of feline A-type RBCs were treated with mPEG at various molecular weights and concentrations. Agglutination tests showed that the coating of feline A-type RBCs with mPEG of 20 kDa and 2 mM blocked hemagglutination to feline anti-A alloantibodies over 8 h. While no differences in RBC size and shape between intact and mPEG-treated RBCs were seen, coating RBCs with mPEG inhibited the binding of feline anti-A alloantibodies. Furthermore, the mPEG-treated RBCs did not cause spontaneous hemolysis or osmotic fragility, compared to control RBCs. According to a monocyte monolayer assay, mPEG treatment significantly reduced feline anti-A antibody-mediated phagocystosis of RBCs. These results confirm the potential of using activated mPEG on feline A-type RBC to create universal erythrocytes for transfusion to B-type cats. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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23 pages, 8232 KiB  
Article
Chitin Conduits with Different Inner Diameters at Both Ends Combined with Dual Growth Factor Hydrogels Promote Nerve Transposition Repair in Rats
by Fengshi Zhang, Bo Ma, Qicheng Li, Meng Zhang and Yuhui Kou
J. Funct. Biomater. 2023, 14(9), 442; https://doi.org/10.3390/jfb14090442 - 28 Aug 2023
Cited by 2 | Viewed by 1432
Abstract
Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. Innovative techniques, such as nerve transposition repair with conduit suturing, can be employed to successfully treat severe peripheral [...] Read more.
Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. Innovative techniques, such as nerve transposition repair with conduit suturing, can be employed to successfully treat severe peripheral nerve damage. However, cylindrical nerve guides are typically unsuitable for nerve transposition repair. Furthermore, angiogenic and neurotrophic factors are necessary to stimulate the emergence of axonal lateral sprouts, proximal growth, and the rehabilitation of neuron structures and functions. In the current study, we used chitosan to make chitin conduits with different inner diameters at both ends, combined with gelatin methacrylate hydrogels that can continuously release dual growth factors, namely, the vascular endothelial growth factor (VEGF) and the nerve growth factor (NGF), and evaluated its impact on nerve transposition repair in rats. At 16 weeks after the operation, our findings showed that the conduit combined with the dual growth factor hydrogel significantly improved the restoration of both motor and conduction functions of the nerve. In addition, histological analysis showed significant recovery of nerve fibers, target muscles, and neurons. In conclusion, the combination of chitin conduits with different inner diameters and dual growth factor hydrogels can significantly improve the effect of nerve transposition repair, which has important potential clinical value. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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16 pages, 6529 KiB  
Article
Modulation of Cell Response through the Covalent Binding of Fibronectin to Titanium Substrates
by Parsa Rezvanian, Aroa Álvarez-López, Raquel Tabraue-Rubio, Rafael Daza, Luis Colchero, Manuel Elices, Gustavo V. Guinea, Daniel González-Nieto and José Pérez-Rigueiro
J. Funct. Biomater. 2023, 14(7), 342; https://doi.org/10.3390/jfb14070342 - 28 Jun 2023
Cited by 3 | Viewed by 1395
Abstract
Titanium (Ti-6Al-4V) substrates were functionalized through the covalent binding of fibronectin, and the effect of the existence of this extracellular matrix protein on the surface of the material was assessed by employing mesenchymal stem cell (MSC) cultures. The functionalization process comprised the usage [...] Read more.
Titanium (Ti-6Al-4V) substrates were functionalized through the covalent binding of fibronectin, and the effect of the existence of this extracellular matrix protein on the surface of the material was assessed by employing mesenchymal stem cell (MSC) cultures. The functionalization process comprised the usage of the activation vapor silanization (AVS) technique to deposit a thin film with a high surface density of amine groups on the material, followed by the covalent binding of fibronectin to the amine groups using the N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) crosslinking chemistry. The biological effect of the fibronectin on murine MSCs was assessed in vitro. It was found that functionalized samples not only showed enhanced initial cell adhesion compared with bare titanium, but also a three-fold increase in the cell area, reaching values comparable to those found on the polystyrene controls. These results provide compelling evidence of the potential to modulate the response of the organism to an implant through the covalent binding of extracellular matrix proteins on the prosthesis. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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22 pages, 4172 KiB  
Article
Green Biodegradable Polylactide-Based Polyurethane Triblock Copolymers Reinforced with Cellulose Nanowhiskers
by Mohamed Khattab, Noha Abdel Hady and Yaser Dahman
J. Funct. Biomater. 2023, 14(3), 118; https://doi.org/10.3390/jfb14030118 - 21 Feb 2023
Cited by 1 | Viewed by 2042
Abstract
A novel series of biodegradable polylactide-based triblock polyurethane (TBPU) copolymers covering a wide range of molecular weights and compositions were synthesized for potential use in biomedical applications. This new class of copolymers showed tailored mechanical properties, improved degradation rates, and enhanced cell attachment [...] Read more.
A novel series of biodegradable polylactide-based triblock polyurethane (TBPU) copolymers covering a wide range of molecular weights and compositions were synthesized for potential use in biomedical applications. This new class of copolymers showed tailored mechanical properties, improved degradation rates, and enhanced cell attachment potential compared to polylactide homopolymer. Triblock copolymers, (TB) PL-PEG-PL, of different compositions were first synthesized from lactide and polyethylene glycol (PEG) via ring-opening polymerization in the presence of tin octoate as the catalyst. After which, polycaprolactone diol (PCL-diol) reacted with TB copolymers using 1,4-butane diisocyanate (BDI) as a nontoxic chain extender to form the final TBPUs. The final composition, molecular weight, thermal properties, hydrophilicity, and biodegradation rates of the obtained TB copolymers, and the corresponding TBPUs were characterized using 1H-NMR, GPC, FTIR, DSC, and SEM, and contact angle measurements. Results obtained from the lower molecular weight series of TBPUs demonstrated potential use in drug delivery and imaging contrast agents due to their high hydrophilicity and degradation rates. On the other hand, the higher molecular weight series of TBPUs exhibited improved hydrophilicity and degradation rates compared to PL-homopolymer. Moreover, they displayed improved tailored mechanical properties suitable for utilization as bone cement, or in regeneration medicinal applications of cartilage, trabecular, and cancellous bone implants. Furthermore, the polymer nanocomposites obtained by reinforcing the TBPU3 matrix with 7% (w/w) bacterial cellulose nanowhiskers (BCNW) displayed a ~16% increase in tensile strength, and 330% in % elongation compared with PL-homo polymer. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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13 pages, 1935 KiB  
Article
Evaluation of the Cytotoxicity of Cationic Polymers on Glioblastoma Cancer Stem Cells
by Conor McCartin, Juliette Blumberger, Candice Dussouillez, Patricia Fernandez de Larrinoa, Monique Dontenwill, Christel Herold-Mende, Philippe Lavalle, Béatrice Heurtault, Stéphane Bellemin-Laponnaz, Sylvie Fournel and Antoine Kichler
J. Funct. Biomater. 2023, 14(1), 17; https://doi.org/10.3390/jfb14010017 - 28 Dec 2022
Cited by 2 | Viewed by 2476
Abstract
Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug [...] Read more.
Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug conjugates (PDCs). Yet a potentially underexplored domain of research is in their inherent potential as anti-cancer therapeutic agents, which has been indicated by several studies. Even more interesting is the recent observation that certain polycations may present a significantly greater toxicity towards the clinically important cancer stem cell (CSC) niche than towards more differentiated bulk tumour cells. These cells, which possess the stem-like characteristics of self-renewal and differentiation, are highly implicated in cancer drug resistance, tumour recurrence and poor clinical prognosis. The search for compounds which may target and eliminate these cells is thus of great research interest. As such, the observation in our previous study on a PEI-based PDC which showed a considerably higher toxicity of PEI towards glioblastoma CSCs (GSCs) than on more differentiated glioma (U87) cells led us to investigate other cationic polymers for a similar effect. The evaluation of the toxicity of a range of different types of polycations, and an investigation into the potential source of GSC’s sensitivity to such compounds is thus described. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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Review

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34 pages, 2665 KiB  
Review
Factors Influencing Properties of Spider Silk Coatings and Their Interactions within a Biological Environment
by Vanessa T. Trossmann, Sarah Lentz and Thomas Scheibel
J. Funct. Biomater. 2023, 14(8), 434; https://doi.org/10.3390/jfb14080434 - 19 Aug 2023
Cited by 8 | Viewed by 2697
Abstract
Biomaterials are an indispensable part of biomedical research. However, although many materials display suitable application-specific properties, they provide only poor biocompatibility when implanted into a human/animal body leading to inflammation and rejection reactions. Coatings made of spider silk proteins are promising alternatives for [...] Read more.
Biomaterials are an indispensable part of biomedical research. However, although many materials display suitable application-specific properties, they provide only poor biocompatibility when implanted into a human/animal body leading to inflammation and rejection reactions. Coatings made of spider silk proteins are promising alternatives for various applications since they are biocompatible, non-toxic and anti-inflammatory. Nevertheless, the biological response toward a spider silk coating cannot be generalized. The properties of spider silk coatings are influenced by many factors, including silk source, solvent, the substrate to be coated, pre- and post-treatments and the processing technique. All these factors consequently affect the biological response of the environment and the putative application of the appropriate silk coating. Here, we summarize recently identified factors to be considered before spider silk processing as well as physicochemical characterization methods. Furthermore, we highlight important results of biological evaluations to emphasize the importance of adjustability and adaption to a specific application. Finally, we provide an experimental matrix of parameters to be considered for a specific application and a guided biological response as exemplarily tested with two different fibroblast cell lines. Full article
(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)
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