Special Issue "Advanced Polymers for Biomedical Applications"

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Biomacromolecules, Biobased and Biodegradable Polymers".

Deadline for manuscript submissions: closed (31 January 2021).

Special Issue Editor

Dr. Luis García-Fernández
E-Mail Website
Guest Editor
1. Institute of Polymer Science and Technology (ICTP-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain
2. Networking Biomedical Research Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain
Interests: antimicrobials; biomaterials; natural polymers; polymers; polymer composites; nanomaterial; scaffold; surface modification; drug delivery; tissue engineering

Special Issue Information

Dear Colleagues,

Polymers are the largest and most versatile class of biomaterials being extensively applied for therapeutic applications. From natural to synthetic polymers, the possibilities to design and modify their physical–chemical properties make these systems of great interest in a wide range of biomedical applications as diverse as drug delivery systems, organ-on-a-chip, diagnostics, tissue engineering, and so on.

In recent years, advances in the synthesis and modification of polymers and characterization techniques have allowed the design of novel biomaterials as well as the study of their biological behavior in vitro and in vivo.

The purpose of this Special Issue is to highlight recent achievements from the synthesis and modifications of polymers for biomedical applications to final applications in the field of biomedicine.

Dr. Luis García-Fernández
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Polymers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hydrogels
  • scaffold
  • drug delivery system
  • tissue engineering
  • polymers
  • natural polymer
  • biomaterial
  • synthesis
  • modification

Published Papers (12 papers)

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Research

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Article
pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation
Polymers 2021, 13(9), 1515; https://doi.org/10.3390/polym13091515 - 08 May 2021
Viewed by 476
Abstract
Polymeric prodrugs, synthesized by conjugating chemotherapeutic agents to functional polymers, have been extensively investigated and employed for safer and more efficacious cancer therapy. By rational design, a pH and reduction dual-sensitive dextran-di-drugs conjugate (oDex-g-Pt+DOX) was synthesized by the covalent conjugation of Pt (IV) [...] Read more.
Polymeric prodrugs, synthesized by conjugating chemotherapeutic agents to functional polymers, have been extensively investigated and employed for safer and more efficacious cancer therapy. By rational design, a pH and reduction dual-sensitive dextran-di-drugs conjugate (oDex-g-Pt+DOX) was synthesized by the covalent conjugation of Pt (IV) prodrug and doxorubicin (DOX) to an oxidized dextran (oDex). Pt (IV) prodrug and DOX were linked by the versatile efficient esterification reactions and Schiff base reaction, respectively. oDex-g-Pt+DOX could self-assemble into nanoparticles with an average diameter at around 180 nm. The acidic and reductive (GSH) environment induced degradation and drug release behavior of the resulting nanoparticles (oDex-g-Pt+DOX NPs) were systematically investigated by optical experiment, DLS analysis, TEM measurement, and in vitro drugs release experiment. Effective cellular uptake of the oDex-g-Pt+DOX NPs was identified by the human cervical carcinoma HeLa cells via confocal laser scanning microscopy. Furthermore, oDex-g-Pt+DOX NPs displayed a comparable antiproliferative activity than the simple combination of free cisplatin and DOX (Cis+DOX) as the extension of time. More importantly, oDex-g-Pt+DOX NPs exhibited remarkable reversal ability of tumor resistance compared to the cisplatin in cisplatin-resistant lung carcinoma A549 cells. Take advantage of the acidic and reductive microenvironment of tumors, this smart polymer-dual-drugs conjugate could serve as a promising and effective nanomedicine for combination chemotherapy. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System
Polymers 2021, 13(6), 982; https://doi.org/10.3390/polym13060982 - 23 Mar 2021
Viewed by 565
Abstract
Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic [...] Read more.
Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic polyglycerol sulfate (DR-dPGS) drug delivery system by copolymerization of glycidol, ε-caprolactone and an epoxide monomer bearing a disulfide bond (SSG), followed by sulfation of terminal hydroxyl groups of the copolymer. The effect of different catalysts, including Lewis acids and organic bases, on the molecular weight, monomer content and polymer structure was investigated. The degradation of the polymer backbone was proven in presence of reducing agents and candida antarctica Lipase B (CALB) enzyme, which results in the cleavage of the disulfides and ester bonds, respectively. The hydrophobic anticancer drug Doxorubicin (DOX) was loaded in the polymer and the kinetic assessment showed an enhanced drug release with glutathione (GSH) or CALB as compared to controls and a synergistic effect of a combination of both stimuli. Cell uptake was studied by using confocal laser scanning microscopy with HeLa cells and showed the uptake of the Dox-loaded carriers and the release of the drug into the nucleus. Cytotoxicity tests with three different cancer cell lines showed good tolerability of the polymers of as high concentrations as 1 mg mL−1, while cancer cell growth was efficiently inhibited by [email protected] Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Assessing the Influence of Dyes Physico-Chemical Properties on Incorporation and Release Kinetics in Silk Fibroin Matrices
Polymers 2021, 13(5), 798; https://doi.org/10.3390/polym13050798 - 05 Mar 2021
Viewed by 625
Abstract
Silk fibroin (SF) is a promising and versatile biodegradable protein for biomedical applications. This study aimed to develop a prolonged release device by incorporating SF microparticles containing dyes into SF hydrogels. The influence of dyes on incorporation and release kinetics in SF based [...] Read more.
Silk fibroin (SF) is a promising and versatile biodegradable protein for biomedical applications. This study aimed to develop a prolonged release device by incorporating SF microparticles containing dyes into SF hydrogels. The influence of dyes on incorporation and release kinetics in SF based devices were evaluated regarding their hydrophilicity, molar mass, and cationic/anionic character. Hydrophobic and cationic dyes presented high encapsulation efficiency, probably related to electrostatic and hydrophobic interactions with SF. The addition of SF microparticles in SF hydrogels was an effective method to prolong the release, increasing the release time by 10-fold. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Effects of Two Melt Extrusion Based Additive Manufacturing Technologies and Common Sterilization Methods on the Properties of a Medical Grade PLGA Copolymer
Polymers 2021, 13(4), 572; https://doi.org/10.3390/polym13040572 - 14 Feb 2021
Viewed by 843
Abstract
Although bioabsorbable polymers have garnered increasing attention because of their potential in tissue engineering applications, to our knowledge there are only a few bioabsorbable 3D printed medical devices on the market thus far. In this study, we assessed the processability of medical grade [...] Read more.
Although bioabsorbable polymers have garnered increasing attention because of their potential in tissue engineering applications, to our knowledge there are only a few bioabsorbable 3D printed medical devices on the market thus far. In this study, we assessed the processability of medical grade Poly(lactic-co-glycolic) Acid (PLGA)85:15 via two additive manufacturing technologies: Fused Filament Fabrication (FFF) and Direct Pellet Printing (DPP) to highlight the least destructive technology towards PLGA. To quantify PLGA degradation, its molecular weight (gel permeation chromatography (GPC)) as well as its thermal properties (differential scanning calorimetry (DSC)) were evaluated at each processing step, including sterilization with conventional methods (ethylene oxide, gamma, and beta irradiation). Results show that 3D printing of PLGA on a DPP printer significantly decreased the number-average molecular weight (Mn) to the greatest extent (26% Mn loss, p < 0.0001) as it applies a longer residence time and higher shear stress compared to classic FFF (19% Mn loss, p < 0.0001). Among all sterilization methods tested, ethylene oxide seems to be the most appropriate, as it leads to no significant changes in PLGA properties. After sterilization, all samples were considered to be non-toxic, as cell viability was above 70% compared to the control, indicating that this manufacturing route could be used for the development of bioabsorbable medical devices. Based on our observations, we recommend using FFF printing and ethylene oxide sterilization to produce PLGA medical devices. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Characterization of Bio-Inspired Electro-Conductive Soy Protein Films
Polymers 2021, 13(3), 416; https://doi.org/10.3390/polym13030416 - 28 Jan 2021
Cited by 1 | Viewed by 540
Abstract
Protein-based conductive materials are gaining attention as alternative components of electronic devices for value-added applications. In this regard, soy protein isolate (SPI) was processed by extrusion in order to obtain SPI pellets, subsequently molded into SPI films by hot pressing, resulting in homogeneous [...] Read more.
Protein-based conductive materials are gaining attention as alternative components of electronic devices for value-added applications. In this regard, soy protein isolate (SPI) was processed by extrusion in order to obtain SPI pellets, subsequently molded into SPI films by hot pressing, resulting in homogeneous and transparent films, as shown by scanning electron microscopy and UV-vis spectroscopy analyses, respectively. During processing, SPI denatured and refolded through intermolecular interactions with glycerol, causing a major exposition of tryptophan residues and fluorescence emission, affecting charge distribution and electron transport properties. Regarding electrical conductivity, the value found (9.889 × 10−4 S/m) is characteristic of electrical semiconductors, such as silicon, and higher than that found for other natural polymers. Additionally, the behavior of the films in contact with water was analyzed, indicating a controlled swelling and a hydrolytic surface, which is of great relevance for cell adhesion and spreading. In fact, cytotoxicity studies showed that the developed SPI films were biocompatible, according to the guidelines for the biological evaluation of medical devices. Therefore, these SPI films are uniquely suited as bioelectronics because they conduct both ionic and electronic currents, which is not accessible for the traditional metallic conductors. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
A Full Set of In Vitro Assays in Chitosan/Tween 80 Microspheres Loaded with Magnetite Nanoparticles
Polymers 2021, 13(3), 400; https://doi.org/10.3390/polym13030400 - 27 Jan 2021
Cited by 1 | Viewed by 896
Abstract
Microspheres have been proposed for different medical applications, such as the delivery of therapeutic proteins. The first step, before evaluating the functionality of a protein delivery system, is to evaluate their biological safety. In this work, we developed chitosan/Tween 80 microspheres loaded with [...] Read more.
Microspheres have been proposed for different medical applications, such as the delivery of therapeutic proteins. The first step, before evaluating the functionality of a protein delivery system, is to evaluate their biological safety. In this work, we developed chitosan/Tween 80 microspheres loaded with magnetite nanoparticles and evaluated cell damage. The formation and physical–chemical properties of the microspheres were determined by FT-IR, Raman, thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), and SEM. Cell damage was evaluated by a full set of in vitro assays using a non-cancerous cell line, human erythrocytes, and human lymphocytes. At the same time, to know if these microspheres can load proteins over their surface, bovine serum albumin (BSA) immobilization was measured. Results showed 7 nm magnetite nanoparticles loaded into chitosan/Tween 80 microspheres with average sizes of 1.431 µm. At concentrations from 1 to 100 µg/mL, there was no evidence of changes in mitochondrial metabolism, cell morphology, membrane rupture, cell cycle, nor sister chromatid exchange formation. For each microgram of microspheres 1.8 µg of BSA was immobilized. The result provides the fundamental understanding of the in vitro biological behavior, and safety, of developed microspheres. Additionally, this set of assays can be helpful for researchers to evaluate different nano and microparticles. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Evaluation of Glycerylphytate Crosslinked Semi- and Interpenetrated Polymer Membranes of Hyaluronic Acid and Chitosan for Tissue Engineering
Polymers 2020, 12(11), 2661; https://doi.org/10.3390/polym12112661 - 11 Nov 2020
Cited by 3 | Viewed by 750
Abstract
In the present study, semi- and interpenetrated polymer network (IPN) systems based on hyaluronic acid (HA) and chitosan using ionic crosslinking of chitosan with a bioactive crosslinker, glycerylphytate (G1Phy), and UV irradiation of methacrylate were developed, characterized and evaluated as potential [...] Read more.
In the present study, semi- and interpenetrated polymer network (IPN) systems based on hyaluronic acid (HA) and chitosan using ionic crosslinking of chitosan with a bioactive crosslinker, glycerylphytate (G1Phy), and UV irradiation of methacrylate were developed, characterized and evaluated as potential supports for tissue engineering. Semi- and IPN systems showed significant differences between them regarding composition, morphology, and mechanical properties after physicochemical characterization. Dual crosslinking process of IPN systems enhanced HA retention and mechanical properties, providing also flatter and denser surfaces in comparison to semi-IPN membranes. The biological performance was evaluated on primary human mesenchymal stem cells (hMSCs) and the systems revealed no cytotoxic effect. The excellent biocompatibility of the systems was demonstrated by large spreading areas of hMSCs on hydrogel membrane surfaces. Cell proliferation increased over time for all the systems, being significantly enhanced in the semi-IPN, which suggested that these polymeric membranes could be proposed as an effective promoter system of tissue repair. In this sense, the developed crosslinked biomimetic and biodegradable membranes can provide a stable and amenable environment for hMSCs support and growth with potential applications in the biomedical field. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Formulation and Evaluation of Microwave-Modified Chitosan-Curcumin Nanoparticles—A Promising Nanomaterials Platform for Skin Tissue Regeneration Applications Following Burn Wounds
Polymers 2020, 12(11), 2608; https://doi.org/10.3390/polym12112608 - 06 Nov 2020
Cited by 3 | Viewed by 821
Abstract
Improved physicochemical properties of chitosan-curcumin nanoparticulate carriers using microwave technology for skin burn wound application are reported. The microwave modified low molecular weight chitosan variant was used for nanoparticle formulation by ionic gelation method nanoparticles analyzed for their physicochemical properties. The antimicrobial activity [...] Read more.
Improved physicochemical properties of chitosan-curcumin nanoparticulate carriers using microwave technology for skin burn wound application are reported. The microwave modified low molecular weight chitosan variant was used for nanoparticle formulation by ionic gelation method nanoparticles analyzed for their physicochemical properties. The antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa cultures, cytotoxicity and cell migration using human dermal fibroblasts—an adult cell line—were studied. The microwave modified chitosan variant had significantly reduced molecular weight, increased degree of deacetylation and decreased specific viscosity. The nanoparticles were nano-sized with high positive charge and good dispersibility with entrapment efficiency and drug content in between 99% and 100%, demonstrating almost no drug loss. Drug release was found to be sustained following Fickian the diffusion mechanism for drug release with higher cumulative drug release observed for formulation (F)2. The microwave treatment does not render a destructive effect on the chitosan molecule with the drug embedded in the core of nanoparticles. The optimized formulation precluded selected bacterial strain colonization, exerted no cytotoxic effect, and promoted cell migration within 24 h post application in comparison to blank and/or control application. Microwave modified low molecular weight chitosan-curcumin nanoparticles hold potential in delivery of curcumin into the skin to effectively treat skin manifestations. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
3D Printing of a Reactive Hydrogel Bio-Ink Using a Static Mixing Tool
Polymers 2020, 12(9), 1986; https://doi.org/10.3390/polym12091986 - 31 Aug 2020
Cited by 10 | Viewed by 1584
Abstract
Hydrogel-based bio-inks have recently attracted more attention for 3D printing applications in tissue engineering due to their remarkable intrinsic properties, such as a cell supporting environment. However, their usually weak mechanical properties lead to poor printability and low stability of the obtained structures. [...] Read more.
Hydrogel-based bio-inks have recently attracted more attention for 3D printing applications in tissue engineering due to their remarkable intrinsic properties, such as a cell supporting environment. However, their usually weak mechanical properties lead to poor printability and low stability of the obtained structures. To obtain good shape fidelity, current approaches based on extrusion printing use high viscosity solutions, which can compromise cell viability. This paper presents a novel bio-printing methodology based on a dual-syringe system with a static mixing tool that allows in situ crosslinking of a two-component hydrogel-based ink in the presence of living cells. The reactive hydrogel system consists of carboxymethyl chitosan (CMCh) and partially oxidized hyaluronic acid (HAox) that undergo fast self-covalent crosslinking via Schiff base formation. This new approach allows us to use low viscosity solutions since in situ gelation provides the appropriate structural integrity to maintain the printed shape. The proposed bio-ink formulation was optimized to match crosslinking kinetics with the printing process and multi-layered 3D bio-printed scaffolds were successfully obtained. Printed scaffolds showed moderate swelling, good biocompatibility with embedded cells, and were mechanically stable after 14 days of the cell culture. We envision that this straightforward, powerful, and generalizable printing approach can be used for a wide range of materials, growth factors, or cell types, to be employed for soft tissue regeneration. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Article
Development of Biocomposite Polymeric Systems Loaded with Antibacterial Nanoparticles for the Coating of Polypropylene Biomaterials
Polymers 2020, 12(8), 1829; https://doi.org/10.3390/polym12081829 - 15 Aug 2020
Cited by 2 | Viewed by 944
Abstract
The development of a biocomposite polymeric system for the antibacterial coating of polypropylene mesh materials for hernia repair is reported. Coatings were constituted by a film of chitosan containing randomly dispersed poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with chlorhexidine [...] Read more.
The development of a biocomposite polymeric system for the antibacterial coating of polypropylene mesh materials for hernia repair is reported. Coatings were constituted by a film of chitosan containing randomly dispersed poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with chlorhexidine or rifampicin. The chlorhexidine-loaded system exhibited a burst release during the first day reaching the release of the loaded drug in three or four days, whereas rifampicin was gradually released for at least 11 days. Both antibacterial coated meshes were highly active against Staphylococcus aureus and Staphylococcus epidermidis (106 CFU/mL), displaying zones of inhibition that lasted for 7 days (chlorhexidine) or 14 days (rifampicin). Apparently, both systems inhibited bacterial growth in the surrounding environment, as well as avoided bacterial adhesion to the mesh surface. These polymeric coatings loaded with biodegradable nanoparticles containing antimicrobials effectively precluded bacterial colonization of the biomaterial. Both biocomposites showed adequate performance and thus could have potential application in the design of antimicrobial coatings for the prophylactic coating of polypropylene materials for hernia repair. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Review

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Review
Emerging Biofabrication Techniques: A Review on Natural Polymers for Biomedical Applications
Polymers 2021, 13(8), 1209; https://doi.org/10.3390/polym13081209 - 08 Apr 2021
Cited by 1 | Viewed by 635
Abstract
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 [...] Read more.
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). Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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Review
Polymer Based Bioadhesive Biomaterials for Medical Application—A Perspective of Redefining Healthcare System Management
Polymers 2020, 12(12), 3015; https://doi.org/10.3390/polym12123015 - 16 Dec 2020
Cited by 1 | Viewed by 729
Abstract
This article deliberates about the importance of polymer-based bioadhesive biomaterials’ medical application in healthcare and in redefining healthcare management. Nowadays, the application of bioadhesion in the health sector is one of the great interests for various researchers, due to recent advances in their [...] Read more.
This article deliberates about the importance of polymer-based bioadhesive biomaterials’ medical application in healthcare and in redefining healthcare management. Nowadays, the application of bioadhesion in the health sector is one of the great interests for various researchers, due to recent advances in their formulation development. Actually, this area of study is considered as an active multidisciplinary research approach, where engineers, scientists (including chemists, physicists, biologists, and medical experts), material producers and manufacturers combine their knowledge in order to provide better healthcare. Moreover, while discussing the implications of value-based healthcare, it is necessary to mention that health comprises three main domains, namely, physical, mental, and social health, which not only prioritize the quality healthcare, but also enable us to measure the outcomes of medical interventions. In addition, this conceptual article provides an understanding of the consequences of the natural or synthetic polymer-based bioadhesion of biomaterials, and its significance for redefining healthcare management as a novel approach. Furthermore, the research assumptions highlight that the quality healthcare concept has recently become a burning topic, wherein healthcare service providers, private research institutes, government authorities, public service boards, associations and academics have taken the initiative to restructure the healthcare system to create value for patients and increase their satisfaction, and lead ultimately to a healthier society. Full article
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
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