Emerging Biofabrication Techniques : A Review on Natural Polymers for Biomedical Applications

Natural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing)

Emerging Biofabrication Techniques: A Review on Natural Polymers for Biomedical Applications

Natural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing)

Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting

Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanoprecipitation and presented hydrodynamic diameters of 100 and 75 nm respectively. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrices. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1) support controlled release of bioactive catechol NPs to the wound site; 2) can incorporate additional therapeutic functions by co-encapsulating drugs; 3) can be printed into 3D scaffolds with tailored geometries based on patient requirements

Contribution of bioactive hyaluronic acid and gelatin to regenerative medicine. Methodologies of gels preparation and advanced applications.

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Bioinspired functional polymers for regenerative medicine: contribution of biomimetic approaches to tissue engineering challenges

La Ingeniería de Tejidos (IT) y la Medicina Regenerativa (MR) son áreas de gran interés y desarrollo en la medicina que han surgido para superar las limitaciones que presentan las metodologías actualmente utilizadas en la reparación de tejidos . Así, los campos de la IT y la MR están relacionados con la regeneración o reparación de tejidos u órganos dañados para restablecer su función biológica regular, centrándose en la estimulación de los mecanismos de reparación propios del cuerpo. La IT es un campo multidisciplinar que reúne conocimientos de los campos de la ciencia y tecnología de los materiales, la biología celular y la ingeniería biomédica para desarrollar dispositivos biomédicos que puedan implantarse en pacientes para inducir la regeneración de tejidos. Los dispositivos biomédicos generalmente combinan un andamio como material de soporte, células vivas y moléculas bioactivas. El andamio actúa esencialmente como plantilla o soporte para proporcionar un entorno celular apropiado que promueva la capacidad nativa de las células para adherirse, migrar, proliferar y diferenciarse dando lugar al crecimiento de nuevo tejido denominado tejido incipiente o equivalente tisular o constructo (del inglés construct). Hoy en día, el desarrollo de nuevas estrategias en IT y MR constituye uno de los principales retos científicos que se espera que tengan un impacto importante en el futuro en la práctica clínica, mejorando la calidad de vida del paciente.Doctorado en Química: Química de Síntesis, Catálisis y Materiales Avanzado

Bioactive and bioadhesive catechol conjugated polymers for tissue regeneration

The effective treatment of chronic wounds constitutes one of the most common worldwide healthcare problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system, avoiding tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent catechol for the continuous quenching of free radicals as well as to control inflammatory response, helping to promote the wound-healing process. This natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels providing also the functionalized polymer with bioadhesion in the moist environment of the human body. To reach that goal, synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules with high yields. The system has demonstrated good biocompatibility, a sustained antioxidant response, an anti-inflammatory effect, an ultraviolet (UV) screen, and bioadhesion to porcine skin, all of these been key features in the wound-healing process. Therefore, these novel mussel-inspired materials have an enormous potential for application and can act very positively, favoring and promoting the healing effect in chronic wounds.This research was funded by CIBER-BBN, Spain and the Spanish Ministry of Economy and Competitivity (project MAT2014-51918-C2-1-R and María Puertas-Bartolomé’s scholarship, and project MAT2017-84277-R).Peer reviewe

Emerging Biofabrication Techniques: A Review on Natural Polymers for Biomedical Applications

Natural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing).This research was funded by the Ministry of Science, Innovation, and Universities (Spain) (MAT2017-84277-R); Apadrina la Ciencia-Ford Foundations (Fellowship of A.M.-B)); and Leibniz ScienceCampus Living Therapeutic Materials (Saarbrücken, Germany).Peer reviewe

Synthesis of a Zinc Hydroxystannate/Sepiolite Hybrid Additive to Avoid Fire Propagation and Reduce Smoke Emission of EPDM Rubber Nanocomposites

A zinc hydroxystannate/sepiolite (SEPZHS) hybrid additive was successfully prepared following a facile wet chemical route synthesis where zinc hydroxystannate (ZHS) nanoparticles were grown on the sepiolite’s surface. SEPZHS particles have a fibrillar structure with ZHS nanoparticles homogeneously dispersed and with significantly smaller particle sizes than the synthesized ZHS nanoparticles alone. Sepiolite and SEPZHS were organically modified and introduced in a basic ethylene propylene diene monomer rubber (EPDM) formulation for cable to evaluate the nanocomposite behavior under direct fire sources. The results confirmed the synergistic effect of the hybrid SEPZHS additive in the formation of a most stable and efficient char barrier, thus improving the flame-retardant behavior of EPDM nanocomposite in terms of heat emission, with reductions of more than 40% in the peak of Heat Release Rate (cone calorimeter test), and smoke suppression, with more than 25% reduction in the Total Smoke Production and Smoke Density parameters (smoke chamber test). Moreover, the addition of sepiolite-based additives increased the mechanical properties (hardness) of the nanocomposites, as a result of the matrix reinforcement. This suggests that the SEPZHS hybrid additive may provide a promising option for a new, cost-effective, eco-friendly, yet efficient flame-retardant solution

Biocompatible and bioadhesive low molecular weight polymers containing long-arm catechol-functionalized methacrylate

Excellent adherence properties of blue mussels have been attributed to a catechol-containing amino acid, L-3,4-dihydroxyphenylalanine. This natural form of adhesion has been a source to develop bioadhesive polymers that adhere to biological interfaces. In this study, we describe a bioinspired approach for preparing bioadhesive and biocompatible materials based on synthetic low molecular weight copolymers of a flexible catechol-functionalized methacrylate (CEMA) and N-vinylcaprolactam. Copolymers with CEMA contents in the range 0.9–13.5 mol% were obtained by radical copolymerization. These systems show good biocompatibility and provide good antioxidant behavior and anti-inflammatory activity. Likewise, hydrogels prepared by mixture of a selected copolymer with gelatin possess good bone bioadhesive properties. These findings show that copolymer composition can be used as a tool for the preparation of biomedical systems with tunable properties and great potential for the development of drug delivery systems and bioactive gels that can be applied in tissue regeneration processes.This work was supported by CIBER-BBN (Spain) and the Spanish Ministry of Economy and Competitiveness [project MAT2014-51918- C2-1-R and M. Puertas-Bartolomé scholarshipPeer Reviewe

Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting

Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanoprecipitation and presented hydrodynamic diameters of 100 and 75 nm respectively. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrices. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1) support controlled release of bioactive catechol NPs to the wound site; 2) can incorporate additional therapeutic functions by co-encapsulating drugs; 3) can be printed into 3D scaffolds with tailored geometries based on patient requirements.Authors thank CIBER-BBN (Spain) and the Spanish Ministry of Economy and Competitivity (M. Puertas-Bartolomé scholarship BES-2015-075161) and the Spanish Ministry of Science and Innovation (PID2020-114086RB-100) for supporting this work. The authors acknowledge RegenHu company, and particularly: Sandro Figi, Dominic Ernst, Michael Kuster and Andreas Scheidegger, for the fruitful collaboration, development and providing the mixing tool. The authors thank Dr. Emmanuel Terriac from INM, Germany for assistance in the confocal imaging. B. Vázquez-Lasa is a member of the SusPlast platform from CSI