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.     

Chitosan–Hydroxycinnamic Acids Conjugates: Emerging Biomaterials with Rising Applications in Biomedicine

Over the past thirty years, research has shown the huge potential of chitosan in biomedical applications such as drug delivery, tissue engineering and regeneration, cancer therapy, and antimicrobial treatments, among others. One of the major advantages of this interesting polysaccharide is its modifiability, which facilitates its use in tailor-made applications. In this way, the molecular structure of chitosan has been conjugated with multiple molecules to modify its mechanical, biological, or chemical properties. Here, we review the conjugation of chitosan with some bioactive molecules: hydroxycinnamic acids (HCAs); since these derivatives have been probed to enhance some of the biological effects of chitosan and to fine-tune its characteristics for its application in the biomedical field. First, the main characteristics of chitosan and HCAs are presented; then, the currently employed conjugation strategies between chitosan and HCAs are described; and, finally, the studied biomedical applications of these derivatives are discussed to present their limitations and advantages, which could lead to proximal therapeutic uses.     

Chitosan/nanocellulose-based bionanocomposite films for controlled betamethasone and silver sulfadiazine delivery

Bionanocomposite films based on chitosan and nanocellulose (nanocrystals or nanofibrils) have gained considerable attention for biomedical applications, especially for wound dressings. However, the development of these films as controlled drug release dressings is still under-exploited. Therefore, this work aimed to design chitosan/nanocellulose-based bionanocomposite films, loaded by betamethasone or silver sulfadiazine, as functional dressings. The films were obtained by solvent casting and characterized by physicochemical, mechanical, barrier properties, in vitro drug release, and antimicrobial activity. The nanocellulose type, physical state, and content caused influence on the film's properties providing different physical, barrier, and drug release profiles. They are semi-occlusive and mechanically resistant; the drug release is controlled, and possesses antimicrobial activity. In conclusion, the developed biodegradable bionanocomposite films are promising as active dressings for controlled drug delivery in the wound site and have specific applications according to their features to treat inflamed and purulent wounds, non-infectious dry wounds, and infectious wounds.     

Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems—State of Knowledge and Future Prospects

Fast advances in polymer science have provided new hydrogels for applications in drug delivery. Among modern drug formulations, polymeric type stimuli-responsive hydrogels (SRHs), also called smart hydrogels, deserve special attention as they revealed to be a promising tool useful for a variety of pharmaceutical and biomedical applications. In fact, the basic feature of these systems is the ability to change their mechanical properties, swelling ability, hydrophilicity, or bioactive molecules permeability, which are influenced by various stimuli, particularly enzymes. Indeed, among a great number of SHRs, enzyme-responsive hydrogels (ERHs) gain much interest as they possess several potential biomedical applications (e.g., in controlled release, drug delivery, etc.). Such a new type of SHRs directly respond to many different enzymes even under mild conditions. Therefore, they show either reversible or irreversible enzyme-induced changes both in chemical and physical properties. This article reviews the state-of-the art in ERHs designed for controlled drug delivery systems (DDSs). Principal enzymes used for biomedical hydrogel preparation were presented and different ERHs were further characterized focusing mainly on glucose oxidase-, β-galactosidase- and metalloproteinases-based catalyzed reactions. Additionally, strategies employed to produce ERHs were described. The current state of knowledge and the discussion were made on successful applications and prospects for further development of effective methods used to obtain ERH as DDSs.     

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.     

Cyclodextrin-Based Polymeric Materials Bound to Corona Protein for Theranostic Applications

Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences. In this review, we emphasize ongoing research in biomedical fields using CD-based centered, pendant, and terminated polymers and their interactions with protein corona for theranostic applications. Overall, a perusal of information concerning this novel approach in biomedicine will help to implement this methodology based on host-guest interaction to improve therapeutic and diagnostic strategies.     

Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges

Recently, poly (?-caprolactone) (PCL) has gained a lot of attention, and shown great potential in biomedical applications. Among synthetic polymers, PCL is one of the easiest to process and manipulate into a large range of shapes and sizes due to its low melting temperature and its superior viscoelastic properties. In this review article the authors focus mainly on the properties of PCL-based biomaterials relevant to drug delivery and tissue engineering applications. The authors provide an insight into the recent developments and challenges of PCL-based biomaterials as a critical component of new therapeutic strategies for many diseases.     

Functional dendrimer–gold nanoparticle hybrids for biomedical applications

Dendrimers are a class of nano‐sized synthetic polymers with a well‐defined composition and regularly branched tree‐like structure produced by stepwise growth. The uniform size, globular shape and tunable surface chemistry make dendrimers versatile nanoscaffolds to encapsulate or stabilize various inorganic (metal, metal oxide, semiconductor) nanoparticles. In the past decade, research interest in dendrimer–inorganic nanoparticle hybrids has evolved from the development of interesting properties to the exploitation of advanced and useful functions. In particular, because gold nanoparticles with controlled morphology and optical properties have been demonstrated to be promising and versatile candidates for a diverse field of biomedical applications including sensing, in vitro and in vivo imaging, drug delivery, diagnostics and therapies, dendrimer–gold nanoparticle hybrids with biocompatibility have recently been intensively investigated for promising biomedical applications due to their controllable structures and dimensions, as well as their desirable internal and/or external functionalities. In this review, we discuss the recent progress regarding the development of functional dendrimer–gold nanoparticle hybrids for biomedical applications. The strategies for the fabrication of various structures of dendrimer–gold nanoparticle hybrids will first be summarized, followed by their biomedical applications in drug and gene delivery, photothermal therapy and combined therapies. © 2018 Society of Chemical Industry     

Poly(4‐vinyl pyridine)‐grafted graphene oxide for drug delivery and antimicrobial applications

Graphene oxide (GO) was covalently functionalized with poly(4‐vinyl pyridine) (P4VP) by atom transfer radical polymerization for drug delivery and antimicrobial applications. The physiochemical properties, chemical structure, composition and morphology of the P4VP‐functionalized GO (GO‐P4VP) were studied. Simple physisorption of a cancer drug, camptothecin (CPT), via π ? π stacking and/or hydrophobic interactions on the GO‐P4VP was tested for drug loading and its release by altering the pH. The GO‐P4VP has low cytotoxicity, and the CPT‐loaded GO‐P4VP exhibited a high potency for killing cancer cells in vitro. Prominent antimicrobial properties against Escherichia coli and Staphylococcus aureus were also observed. Thus, the GO‐P4VP can be utilized as a drug delivery vector with high biocompatibility, solubility and stability in physiological solutions, a suitable payload capacity and excellent bacterial toxicity. Owing to its small size, low cost, large specific area, ready scalability and useful non‐covalent interactions, GO‐P4VP is a novel material for biomedical, industrial and environmental applications. © 2015 Society of Chemical Industry     

Emerging Perspectives in the Synthesis of Novel Degradable Biomedical Copolymers

Biodegradable polymer is playing an increasingly significant role in the development of biomedical materials due to its good biocompatibility and biodegradability, and is undoubtedly the focus in the biomedical fields, such as controlled drug delivery, tissue engineering, and regenerative medicine. In this review, some new degradable biomedical copolymers reported over the past 5 years are introduced and discussed in combination with some our research results. The molecular design, chemical structures and related properties of these novel biodegradable copolymers are reported. In summarizing the review, the development, potential applications and future directions of the degradable biomedical copolymers are discussed.     

Polymeric nanostructured materials for biomedical applications

Polymeric nanostructured materials (PNMs), which are polymeric materials in nanoscale or polymer composites containing nanomaterials, have become increasingly useful for biomedical applications. In specific, advances in polymer-related nanoscience and nanotechnology have brought a revolutionary change to produce new biomaterials with tailored properties and functionalities for targeted biomedical applications. These materials, including micelles, polymersomes, nanoparticles, nanocapsules, nanogels, nanofibers, dendrimers and nanocomposites, have been widely used in drug delivery, gene therapy, bioimage, tissue engineering and regenerative medicine. This review presents a comprehensive overview on the various types of PNMs, their fabrication methods and biomedical applications, as well as the challenges in research and development of future PNMs.     

自组装肽基纳米材料运载药物和基因的研究进展

肽基分子自组装以其丰富的自组装驱动力、新颖的自组装体纳米结构、自组装体的特殊功能及良好的生物相容性等,在纳米生物材料、护肤和化妆产品、药物传输释放、组织工程支架材料等方面有着广泛的应用前景。由天然氨基酸组成的自组装短肽具有良好的低细胞毒性,可控的降解性能,高的运载效率及细胞摄取率,同时还具有降低药物的毒副作用等优点。因此,它在作为药物和基因的纳米载药材料方面有着巨大的发展前景。使用自组装肽基材料形成的纳米载体对疏水性抗癌药物、蛋白质药物及基因等进行传递释放已成为生物医药学领域的研究重点,因此,对近年来自组装肽基纳米材料作为药物和基因载体在生物医药学上的研究进展做了综述。     

Synthesis, properties and biomedical applications of poly(glycerol sebacate) (PGS): A review

Poly(glycerol sebacate) (PGS) is a biodegradable polymer increasingly used in a variety of biomedical applications. This polyester is prepared by polycondensation of glycerol and sebacic acid. PGS exhibits biocompatibility and biodegradability, both highly relevant properties in biomedical applications. PGS also involves cost effective production with the possibility of up scaling to industrial production. In addition, the mechanical properties and degradation kinetics of PGS can be tailored to match the requirements of intended applications by controlling curing time, curing temperature, reactants concentration and the degree of acrylation in acrylated PGS. Because of the flexible and elastomeric nature of PGS, its biomedical applications have mainly targeted soft tissue replacement and the engineering of soft tissues, such as cardiac muscle, blood, nerve, cartilage and retina. However, applications of PGS are being expanded to include drug delivery, tissue adhesive and hard tissue (i.e., bone) regeneration. The design and fabrication of PGS based devices for applications that mimic native physiological conditions are also being pursued. Novel designs range from accordion-like honeycomb structures for cardiac patches, gecko-like surfaces for tissue adhesives to PGS (nano) fibers for extra cellular matrix (ECM) like constructs; new design avenues are being investigated to meet the ever growing demand for replacement tissues and organs. In less than a decade PGS has become a material of great scrutiny and interest by the biomedical research community. In this review we consolidate the valuable existing knowledge in the fields of synthesis, properties and biomedical applications of PGS and PGS-related biomaterials and devices.     

Review of crosslinked and non‐crosslinked copolyesters for tissue engineering and drug delivery

Novel degradable biomedical materials are found to have huge potential applications in fields such as drug delivery and release, orthopedic fixation support and tissue engineering. Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. In this review, some new degradable biomedical copolyesters reported in recent years are introduced and discussed in combination with some of our research results, including non‐crosslinked copolyesters, crosslinked copolyesters and their corresponding derivatives. The molecular design, chemical structures and related properties of these biodegradable copolyesters are reported. In summarizing the review, the development, potential applications and future directions of degradable biomedical copolyesters are discussed. © 2013 Society of Chemical Industry     

An Update on Graphene-Based Nanomaterials for Neural Growth and Central Nervous System Regeneration

Thanks to their reduced size, great surface area, and capacity to interact with cells and tissues, nanomaterials present some attractive biological and chemical characteristics with potential uses in the field of biomedical applications. In this context, graphene and its chemical derivatives have been extensively used in many biomedical research areas from drug delivery to bioelectronics and tissue engineering. Graphene-based nanomaterials show excellent optical, mechanical, and biological properties. They can be used as a substrate in the field of tissue engineering due to their conductivity, allowing to study, and educate neural connections, and guide neural growth and differentiation; thus, graphene-based nanomaterials represent an emerging aspect in regenerative medicine. Moreover, there is now an urgent need to develop multifunctional and functionalized nanomaterials able to arrive at neuronal cells through the blood-brain barrier, to manage a specific drug delivery system. In this review, we will focus on the recent applications of graphene-based nanomaterials in vitro and in vivo, also combining graphene with other smart materials to achieve the best benefits in the fields of nervous tissue engineering and neural regenerative medicine. We will then highlight the potential use of these graphene-based materials to construct graphene 3D scaffolds able to stimulate neural growth and regeneration in vivo for clinical applications.     

Surface Modification of Bacterial Cellulose for Biomedical Applications

Bacterial cellulose is a naturally occurring polysaccharide with numerous biomedical applications that range from drug delivery platforms to tissue engineering strategies. BC possesses remarkable biocompatibility, microstructure, and mechanical properties that resemble native human tissues, making it suitable for the replacement of damaged or injured tissues. In this review, we will discuss the structure and mechanical properties of the BC and summarize the techniques used to characterize these properties. We will also discuss the functionalization of BC to yield nanocomposites and the surface modification of BC by plasma and irradiation-based methods to fabricate materials with improved functionalities such as bactericidal capabilities.     

Alginate: properties and biomedical applications

Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.     

Polyphosphazenes—A Promising Candidate for Drug Delivery,Bioimaging, and Tissue Engineering: A Review

Synthetic polymer materials have been surged to the forefront of research in the fields of tissue engineering, drug delivery, and biomonitoring in recent years. Biodegradable synthetic polymers are increasingly needed as transient substrates for tissue regeneration and medicine delivery. In contrast to commonly used polymers including polyesters, polylactones, polyanhydrides, poly(propylene fumarates), polyorthoesters, and polyurethanes, biodegradable polyphosphazenes (PPZs) hold great potential for the purposes indicated above. PPZ's versatility in the synthetic process has enabled the production of a variety of polymers with various physico-chemical, and biological properties have been produced, making them appropriate for biomedical applications. Biocompatible PPZs are often used as scaffolds in the regeneration of skeleton, bones, and other tissues. PPZs have also received special attention as potential drug vehicles of high-value biopharmaceuticals such as anticancer drugs. Additionally, by incorporating fluorophores into the PPZ backbone to produce photoluminescent biodegradable PPZs, the utility of polyphosphazenes is further expanded as they are used in tracking the regeneration of the target tissue as well as the fate of PPZ based scaffolds or drug delivery vehicles. This review provides a summary of the evolution of PPZ applications in the fields of tissue engineering, drug delivery, and bioimaging in recent 5 years.     

Chitin and chitosan in selected biomedical applications

Chitin (CT), the well-known natural biopolymer and chitosan (CS) (bio-based or “artificial polymer”) are non-toxic, biodegradable and biocompatible in nature. The advantages of these biomaterials are such that, they can be easily processed into different forms such as membranes, sponges, gels, scaffolds, microparticles, nanoparticles and nanofibers for a variety of biomedical applications such as drug delivery, gene therapy, tissue engineering and wound healing. Present review focuses on the diverse applications of CT and CS membranes and scaffolds for drug delivery, tissue engineering and targeted regenerative medicine. The chitinous scaffolds of marine sponges’ origin are discussed here for the first time. These CT based scaffolds obtained from Porifera possess remarkable and unique properties such as hydration, interconnected channels and diverse structural architecture. This review will provide a brief overview of CT and CS membranes and scaffolds toward different kinds of delivery applications such as anticancer drug delivery, osteogenic drug delivery, and growth factor delivery, because of their inimitable release behavior, degradation profile, mucoadhesive nature, etc. The review also provides an overview of the key features of CT and CS membranes and scaffolds such as their biodegradability, cytocompatibility and mechanical properties toward applications in tissue engineering and wound healing.     

酶催化超分子自组装及其在癌症诊疗中的应用研究进展

自组装是自然界的普遍现象,也是构建超分子生物材料的有力工具。在众多方法中,酶催化超分子自组装具有优异的肿瘤靶向性及良好的生物安全性,是近年来癌症诊疗的一个重要新方向。针对这一趋势,本文简介了酶催化超分子自组装在细胞内、外的构建方法,详细总结了其在癌症诊疗中的应用。研究表明,酶催化超分子自组装材料在生物医学成像、选择性杀死癌细胞、药物递送和克服药物不良反应方面具有潜在的应用价值。提出了体内超分子组装体的微观形貌需要明确表征、构建自组装方法的酶范围需要扩展以及需要探索酶催化超分子自组装（EISA）与亚细胞器的相互作用等解决其发展中的问题的思路和方向,并对其在抗菌药物开发、免疫调节、创伤修复和组织再生领域的潜在应用作出了展望。