Biodegradable synthetic polymers: Preparation, functionalization and biomedical application

Biodegradable polymers have been widely used and have greatly promoted the development of biomedical fields because of their biocompatibility and biodegradability. The development of biotechnology and medical technology has set higher requirements for biomedical materials. Novel biodegradable polymers with specific properties are in great demand. Biodegradable polymers can be classified as natural or synthetic polymers according to the source. Synthetic biodegradable polymers have found more versatile and diverse biomedical applications owing to their tailorable designs or modifications. This review presents a comprehensive introduction to various types of synthetic biodegradable polymers with reactive groups and bioactive groups, and further describes their structure, preparation procedures and properties. The focus is on advances in the past decade in functionalization and responsive strategies of biodegradable polymers and their biomedical applications. The possible future developments of the materials are also discussed.     

Preparation，properties and applications of hydroxyapatite/synthetic polymer composites

随着生物医用材料的需求量日趋增大,磷灰石与人工合成高分子的复合材料成为组织修复和替代材料的研究热点。以不同单体分类,综述了磷灰石与合成的非降解高分子、可降解高分子复合材料的研究进展;对羟基磷灰石/合成高分子复合材料的制备方法、性能及其应用等方面进行研究,并对此复合材料存在的问题和发展前景进行讨论。说明从分子水平设计出具有良好力学性能、生物活性和生物相容性的医学材料,具有十分重要的意义。     

In Vitro and In Vivo Characterization of Biodegradable Poly(organophosphazenes) for Biomedical Applications

The need and the growing interest in polymers as biomaterials have led to the synthesis of new polymers with a variety of physico-chemical properties. Biomedical application of such materials not only depends on their physical properties but also on biocompatibility and biodegradability. Polyphosphazenes are a family of ‘hybrid inorganic–organic polymers’ with inorganic elements in the backbone and organic side-groups. The polyphosphazenes constitute a family of greatly diverse performance materials with a broad spectrum of properties. The present review focuses on the biodegradable polyphosphazenes, their biocompatibility, and degradation behavior both in vitro and in vivo. This review also covers the use of biodegradable polyphosphazenes as controlled release devices.     

Materials Based on Quaternized Polysulfones with Potential Applications in Biomedical Field: Structure–Properties Relationship

Starting from the bactericidal properties of functionalized polysulfone (PSFQ) and due to its excellent biocompatibility, biodegradability, and performance in various field, cellulose acetate phthalate (CAP) and polyvinyl alcohol (PVA), as well as their blends (PSFQ/CAP and PSFQ/PVA), have been tested to evaluate their applicative potential in the biomedical field. In this context, because the polymer processing starts from the solution phase, in the first step, the rheological properties were followed in order to assess and control the structural parameters. The surface chemistry analysis, surface properties, and antimicrobial activity of the obtained materials were investigated in order to understand the relationship between the polymers’ structure–surface properties and organization form of materials (fibers and/or films), as important indicators for their future applications. Using the appropriate organization form of the polymers, the surface morphology and performance, including wettability and water permeation, were improved and controlled—these being the desired and needed properties for applications in the biomedical field. Additionally, after antimicrobial activity testing against different bacteria strains, the control of the inhibition mechanism for the analyzed microorganisms was highlighted, making it possible to choose the most efficient polymers/blends and, consequently, the efficiency as biomaterials in targeted applications.     

Reproducible,biocompatible medical materials from biologically derived polysaccharides: Processing and Characterization

Natural polysaccharides like chitosan and dextran have garnered considerable interest in biomedical applications due to their biocompatibility, biodegradability, and nontoxicity. Nonetheless, the development of a reproducible class of medical devices from these materials is challenging and has had limited success. Chitosan and dextran are inherently variable and synthesis using these materials is prone to inconsistencies. In this study, we put forward a robust product development regimen that allows these natural materials to be developed into a reproducible class of biomaterials. First, an array of validated characterization methods (Proton Nuclear Magnetic Resonance, titrations, Ultraviolet spectroscopy, Size Exclusion Chromatography—Multi-Angle Light Scattering, Size Exclusion Chromatography—Refractive Index, and proprietary methods) were developed that allowed rigorous specifications to be set for unprocessed chitosan and dextran, chitosan and dextran intermediates, and chemically modified materials—acrylated chitosan (aCHN) and oxidized dextran (oDEX). Second, a robust and reproducible synthesis scheme involving various in-process controls was developed to chemically modify the unprocessed polysaccharides. Third, purification methods to remove byproducts and low-molecular-weight impurities for both aCHN and oDEX were developed. The study presents a viable strategy for converting variable, natural materials into a reproducible class of biomaterials that can be applied in various biomedical applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48454.     

Biodegradable zinc-based materials with a polymer coating designed for biomedical applications

Over the last decades, biodegradable metals have gained popularity for biomedical applications due to their ability to assist in tissue healing. These materials degrade in vivo, while the corrosion products formed are either absorbed or excreted by the body, and no further surgical intervention is required for removal. Intensive research has been carried out mainly on degradable biomaterials based on Mg and Fe. In recent years, zinc-based degradable biomaterials have been explored by the biomedical community for their intrinsic physiological relevance, desirable biocompatibility, intermediate degradation rate, tuneable mechanical properties and pro-regeneration properties. Since pure Zn does not exhibit sufficient mechanical properties for orthopedic applications, various Zn alloys with better properties are being developed. In this work, the combined effect of minor Fe addition to Zn and a polyethyleneglycol (PEG) coating on the surface morphology, degradation, cytotoxicity and mechanical properties of Zn-based materials was studied. There are several studies regarding the influence of the production of Zn alloys, but the effect of polymer coating on the properties of Zn-based materials has not been reported yet. A positive effect of Fe addition and polymer coating on the degradation rate and mechanical properties was observed. However, a reduction in biocompatibility was also detected.     

Perspectives and Problems of Blood Compatible Polymers

The application of various polymers, both synthetic and natural, for biomedical purposes has made such tremendous progress during the last two decades that a wide variety of biomaterials and blood-contacting devices are currently being used in cardiovascular, orthopaedic, and dental applications throughout the world. Implantation of heart valves, catheters, etc. has become more or less a routine affair in cardiovascular surgery. Most of these devices are being fabricated from polymers, and the basic requirements for developing such a biocompatible polymer are very rigid. It has to be sterilizable, nontoxic, easily fabricable, highly resistant to mechanical strains, should not produce allergy or hypersensitivity, not incite any inflammatory response, and also should not degrade chemically [1].     

Surface Engineering Strategies to Enhance the In Situ Performance of Medical Devices Including Atomic Scale Engineering

Decades of intense scientific research investigations clearly suggest that only a subset of a large number of metals, ceramics, polymers, composites, and nanomaterials are suitable as biomaterials for a growing number of biomedical devices and biomedical uses. However, biomaterials are prone to microbial infection due to Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), hepatitis, tuberculosis, human immunodeficiency virus (HIV), and many more. Hence, a range of surface engineering strategies are devised in order to achieve desired biocompatibility and antimicrobial performance in situ. Surface engineering strategies are a group of techniques that alter or modify the surface properties of the material in order to obtain a product with desired functionalities. There are two categories of surface engineering methods: conventional surface engineering methods (such as coating, bioactive coating, plasma spray coating, hydrothermal, lithography, shot peening, and electrophoretic deposition) and emerging surface engineering methods (laser treatment, robot laser treatment, electrospinning, electrospray, additive manufacturing, and radio frequency magnetron sputtering technique). Atomic-scale engineering, such as chemical vapor deposition, atomic layer etching, plasma immersion ion deposition, and atomic layer deposition, is a subsection of emerging technology that has demonstrated improved control and flexibility at finer length scales than compared to the conventional methods. With the advancements in technologies and the demand for even better control of biomaterial surfaces, research efforts in recent years are aimed at the atomic scale and molecular scale while incorporating functional agents in order to elicit optimal in situ performance. The functional agents include synthetic materials (monolithic ZnO, quaternary ammonium salts, silver nano-clusters, titanium dioxide, and graphene) and natural materials (chitosan, totarol, botanical extracts, and nisin). This review highlights the various strategies of surface engineering of biomaterial including their functional mechanism, applications, and shortcomings. Additionally, this review article emphasizes atomic scale engineering of biomaterials for fabricating antimicrobial biomaterials and explores their challenges.     

Silicone-based biomaterials for biomedical applications: Antimicrobial strategies and 3D printing technologies

Silicone is a synthetic polymer widely used in the biomedical industry as implantable devices since 1940, owing to its excellent mechanical properties and biocompatibility. Silicone biomaterials are renowned for their biocompatibility due to their inert nature and hydrophobic surface. A timeline illustration shows critical development periods of using silicone in varied biomedical applications. In this review, silicone properties are discussed along with several biomedical applications, including medical inserts, speciality contact lenses, drains and shunts, urinary catheters, reconstructive gel fillers, craniofacial prosthesis, nerve conduits, and metatarsophalangeal joint implants. Silicones are prone to microbial infections when exposed and interactions with the host tissue. As in the case of medical inserts, the development of specific antimicrobial strategies is essential. The review highlights silicone implants' interaction with soft and bone tissue and various antimicrobial strategies, including surface coating, physical or chemical modifications, treating with antibiotics or plasma-activated surfaces to develop the resistance to bacterial infection. Finally, 3D printing technology, tissue engineering, regenerative medicine applications, and future trends are also critically presented, indicating the silicone's potential as a biomaterial.     

Ionomer‐based polyurethanes: a comparative study of properties and applications

Polyurethanes cover a large range of materials exhibiting various physical and mechanical properties making them useful in different applications such as elastomers or biomaterials, for instance. The introduction of ionic groups in the polyurethane backbone opens the way to new applications where the ionic groups can act as physical crosslinkers that greatly modify the final mechanical and thermal properties of the materials. Furthermore, the hydrophilicity of the chains can be enhanced by the presence of the ionic species, and so the materials can be processed as conventional dispersions even in a polar solvent such as water. As a consequence the applications are numerous; the main commercial outlets are focused on coatings and textiles industries where they can be used as waterproof coatings or substitutes for leather. But these materials can also be used in high‐tech industries for shape memory materials, biomedical devices and biocompatible materials. This review summarizes the latest developments of this class of promising materials and provides the reader with the potentialities of these polymers in various areas.     

Biomedical applications of boronic acid polymers

Boron-containing organic compounds have found widespread use in synthetic organic chemistry. More recently, boronic acid-containing polymers have proven valuable in a variety of biomedical applications, including the treatment of HIV, obesity, diabetes, and cancer. However, as compared to many other classes of functional polymers, boronic acid-containing (co)polymers remain underutilized, despite their unique reactivity, solubility, and responsive nature. This Feature Article highlights research in this area, with particular focus on recent developments in synthesis, processing, and materials development that have enabled the preparation of new biomaterials. In addition to providing an overview to the current state of the art, we emphasize the versatility of boronic acid polymers and suggest routes for their further employment in other potential biomedical applications.     

Review on rubbers in medicine: natural,silicone and polyurethane rubbers

Abstract

Natural, silicone and polyurethane rubbers are considered as three important biomaterials which have found widespread applications in medical technology. Biocompatibility, biodurability, sterilisability, processibility, as well as mechanical properties, such as flexibility and resilience, are properties that make these kinds of rubbers appropriate candidates for medical applications. Medical devices based on natural rubber, silicone and polyurethane rubbers include cardiac pacemaker leads, mammary prostheses, artificial skin, catheters, denture liners, diaphragms, blood pressure cuff coil, tubes and seals. These types of rubbers are commonly used in controlled drug delivery systems as a carrier for pharmaceutical agents and in the fabrication of other medical devices. These polymers were evaluated for release of hormones (e.g. estradiol and progesterone), metronidazole, nonoxynol-9, etc. In this paper, some recent advances on the development of these polymers in the biomedical field and some reports on the modification and improvement of their properties such as drug release and mechanical properties are reviewed.     

The synthesis,mechanisms, and additives for bio-compatible polyvinyl alcohol hydrogels: A review on current advances,trends, and future outlook

Vinyl polymers are widely used in biological, textile and industrial applications and are currently attracting research attention for specialized bio-based applications. Polyvinyl alcohol (PVA) hydrogels show great advantages as a material with high biocompatibility, permeability, hydrophilicity, and low-friction coefficient, allowing applications as smart materials, wound dressings, and flexible sensors. However, the poor mechanical properties of PVA hydrogels and biocompatibility less than natural polymers make them unsuitable in practical applications. Additives are often added to PVA hydrogels to enhance mechanical properties, endow more compatibility, functionality and expand their application range. Among them, bio-additives such as nanocellulose, natural polysaccharides and proteins are biodegradable, biocompatible, and inexpensive, broadening their applications in the biomedical and tissue engineering fields. This work reviews the synthesis of PVA hydrogels, methods to enhance their mechanical properties, types of bio-additives incorporated for biocompatibility, their mechanism of interaction with PVA and future prospects of PVA composite bio-hydrogels for application in various fields. Representative cases are carefully selected and discussed with regard to their composition and pros and cons are discussed. Finally, future requirements, as well as the opportunities and challenges of these bio-additives for improving the multifunctionality of PVA hydrogels are also presented.     

A comparative assessment of poly(vinylidene fluoride)/conducting polymer electrospun nanofiber membranes for biomedical applications

Piezoelectric polymers, especially poly(vinylidene fluoride) (PVDF) are increasingly receiving interest as smart biomaterials for tissue engineering, energy harvesting, microfluidic, actuator, and biosensor applications. Despite possessing the greatest piezoelectric coefficients among all piezoelectric polymers, it is often desirable to increase the electrical outputs from PVDF for several of these applications. Blending with intrinsically conducting polymers (CP) in the form of nanofiber membranes is one of the facile methods to achieve the same. However, these polymers and their composites have so far been primarily investigated only for their physical property enhancements and in applications like energy storage while their biomedical applications and comparative assessment of their biocompatibility properties have not been yet explored. In this report, electrospinning of PVDF blends with polypyrrole (PPy), polyaniline (PANI), and a modified PANI with l -glutamic acid (PANI-LGA/P-LGA) is performed to obtain different electrically active material membranes. The PVDF:CP composite nanofibers are compared with respect to their nanostructures, β-phase content, and electrical conductivity. Further, biocompatibility of all the membranes was compared. It was found that incorporation of PPy, PANI, and P-LGA increased the electrical conductivity of PVDF while the β-phase content was also substantially enhanced. The highest biocompatibility with a pre-osteoblast cell line (MC3T3) was exhibited in the order p-LGA/PVDF > PANI/PVDF > PPy/PVDF, all being significantly higher than PVDF (p < .001). Although P-LGA/PVDF showed higher electrical conductivity, biocompatibility with MC3T3, it was found to be highly cytotoxic to a HeLa (cancer) cell line. It is concluded that such structure property relations would help in selection of materials for specific biomaterial applications.     

Marine biological waste as a source of hydroxyapatite for bone tissue engineering applications

The demand for bone graft substitutes for orthopedics and dentistry is constantly growing due to the increase of ageing-related diseases. Synthetic hydroxyapatite (HA) is largely used as a bone graft material thanks to its biocompatibility, osteointegration, osteoconductive and osteoinductive properties and similarity to biological apatite, the main mineral component of bones and teeth. Biogenic apatite has gained attention due to its peculiar intrinsic characteristics: multi-doped ion composition and micro- and nano-scale architecture make natural-derived HA particularly promising for biomedical applications.At the same time, the growing interest in green materials is pushing towards the use of more sustainable biomaterials precursors, including re-use materials: marine waste, such as mollusk-shells, shellfish carapaces, cuttlefish bone, and fishbone have become widely studied sources of biogenic HA. Indeed, they are rich in calcium carbonate (CaCO₃), which can be converted into HA by environmentally sustainable processes. This allows the transformation of waste into valuable materials, while paying attention to the issues of sustainability and circular economy.In this review, we listed and discussed the methods to produce HA starting from shell-derived CaCO₃, describing all the steps and synthesis routes proposed for the conversion procedure, with a special focus on the different species of marine shells used. We discussed the use of HA alone or in combination with other materials (natural and synthetic polymers), used to enhance the mechanical and biological properties.We summarized the types of devices obtained by marine-derived HA, including nanorods, particulates and scaffolds and we described their in vitro and in vivo behavior.The up-to-date literature was summarized in tables with a special focus on the in vitro and in vivo biological evaluation of such materials.In conclusion, composite biomaterials based on marine-derived biogenic HA are reported as potential candidates for synthetic bone substitutes highlighting their potential, limitations and future perspectives.     

Recent advances in nanocellulose for biomedical applications

Nanocellulose materials have undergone rapid development in recent years as promising biomedical materials because of their excellent physical and biological properties, in particular their biocompatibility, biodegradability, and low cytotoxicity. Recently, a significant amount of research has been directed toward the fabrication of advanced cellulose nanofibers with different morphologies and functional properties. These nanocellulose fibers are widely applied in medical implants, tissue engineering, drug delivery, wound‐healing, cardiovascular applications, and other medical applications. In this review, we reflect on recent advancements in the design and fabrication of advanced nanocellulose‐based biomaterials (cellulose nanocrystals, bacterial nanocellulose, and cellulose nanofibrils) that are promising for biomedical applications and discuss material requirements for each application, along with the challenges that the materials might face. Finally, we give an overview on future directions of nanocellulose‐based materials in the biomedical field. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41719.     

Stimuli-Responsive Natural Proteins and Their Applications

Natural proteins are essential biomacromolecules that fulfill versatile functions in the living organism, such as their usage as cytoskeleton, nutriment transporter, homeostasis controller, catalyzer, or immune guarder. Due to the excellent mechanical properties and good biocompatibility/biodegradability, natural protein-based biomaterials are well equipped for prospective applications in various fields. Among these natural proteins, stimuli-responsive proteins can be reversibly and precisely manipulated on demand, rendering the protein-based biomaterials promising candidates for numerous applications, including disease detection, drug delivery, bio-sensing, and regenerative medicine. Therefore, we present some typical natural proteins with diverse physical stimuli-responsive properties, including temperature, light, force, electrical, and magnetic sensing in this review. The structure-function mechanism of these proteins is discussed in detail. Finally, we give a summary and perspective for the development of stimuli-responsive proteins.     

Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering

Studies related to biomaterials that stimulate the repair of living tissue have increased considerably, improving the quality of many people's lives that require surgery due to traumatic accidents, bone diseases, bone defects, and reconstructions. Among these biomaterials, bioceramics and bioactive glasses (BGs) have proved to be suitable for coating materials, cement, scaffolds, and nanoparticles, once they present good biocompatibility and degradability, able to generate osteoconduction on the surrounding tissue. However, the role of biomaterials in hard tissue engineering is not restricted to a structural replacement or for guiding tissue regeneration. Nowadays, it is expected that biomaterials develop a multifunctional role when implanted, orchestrating the process of tissue regeneration and providing to the body the capacity to heal itself. In this way, the incorporation of specific metal ions in bioceramics and BGs structure, including magnesium, silver, strontium, lithium, copper, iron, zinc, cobalt, and manganese are currently receiving enhanced interest as biomaterials for biomedical applications. When an ion is incorporated into the bioceramic structure, a new category of material is created, which has several unique properties that overcome the disadvantages of primitive material and favors its use in different biomedical applications. The doping can enhance handling properties, angiogenic and osteogenic performance, and antimicrobial activity. Therefore, this review aims to summarize the effect of selected metal ion dopants into bioceramics and silicate-based BGs in bone tissue engineering. Furthermore, new applications for doped bioceramics and BGs are highlighted, including cancer treatment and drug delivery.     

Recent Advances in Food-Packing,Pharmaceutical and Biomedical Applications of Zein and Zein-Based Materials

Zein is a biodegradable and biocompatible material extracted from renewable resources; it comprises almost 80% of the whole protein content in corn. This review highlights and describes some zein and zein-based materials, focusing on biomedical applications. It was demonstrated in this review that the biodegradation and biocompatibility of zein are key parameters for its uses in the food-packing, biomedical and pharmaceutical fields. Furthermore, it was pointed out that the presence of hydrophilic-hydrophobic groups in zein chains is a very important aspect for obtaining material with different hydrophobicities by mixing with other moieties (polymeric or not), but also for obtaining derivatives with different properties. The physical and chemical characteristics and special structure (at the molecular, nano and micro scales) make zein molecules inherently superior to many other polymers from natural sources and synthetic ones. The film-forming property of zein and zein-based materials is important for several applications. The good electrospinnability of zein is important for producing zein and zein-based nanofibers for applications in tissue engineering and drug delivery. The use of zein’s hydrolysate peptides for reducing blood pressure is another important issue related to the application of derivatives of zein in the biomedical field. It is pointed out that the biodegradability and biocompatibility of zein and other inherent properties associated with zein’s structure allow a myriad of applications of such materials with great potential in the near future.     

Advancements in MXene-Polymer composites for various biomedical applications

2D materials have brought about significant technological advancements in the field of biomaterials. ‘MXene’, a ceramic-based 2D nanomaterial, is comprised of transition metal carbides, nitrides, and carbonitrides having a planar structure educed from a ceramic ‘MAX’ phase by etching out ‘A’ from it, has emerged to surpass drawbacks of conventional biomaterials. In spite of their substantial properties like large surface area, biocompatibility, hydrophilicity, metallic conductivity, and size tunability, the use of MXene is restricted in biomedical applications due of its poor stability in physiological environments, lack of sustained and controlled drug release, and low biodegradability, and these limitations lead to the notion of adopting MXene/Polymer nanocomposites. The availability of functional groups on the surface of MXenes enables polymer functionalization. These polymers functionalized MXene nanocomposites exhibit high photothermal conversion efficiency, selectivity, and stimuli-responsiveness towards malignant cells, electron sensitivity, higher antibacterial properties, and the like. This review emphasizes the innovative exemplars of polymer functionalized MXene composites for the burgeoning biomedical applications, which include controlled and sustained drug delivery, antibacterial activity, photothermal cancer therapy, unambiguous biosensing, contrast-enhanced diagnostic imaging, and bone regeneration.