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/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.     

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.     

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.     

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.     

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。     

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.     

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。     

Polybetaines in Biomedical Applications

Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups) situated in the same structural unit represent an important class of smart polymers with unique and specific properties, belonging to the family of zwitterionic materials. According to the anionic groups, polybetaines can be divided into three major classes: poly(carboxybetaines), poly(sulfobetaines) and poly(phosphobetaines). The structural diversity of polybetaines and their special properties such as, antifouling, antimicrobial, strong hydration properties and good biocompatibility lead to their use in nanotechnology, biological and medical fields, water remediation, hydrometallurgy and the oil industry. In this review we aimed to highlight the recent developments achieved in the field of biomedical applications of polybetaines such as: antifouling, antimicrobial and implant coatings, wound healing and drug delivery systems.     

Graphene: a versatile nanoplatform for biomedical applications

Graphene, with its excellent physical, chemical, and mechanical properties, holds tremendous potential for a wide variety of biomedical applications. As research on graphene-based nanomaterials is still at a nascent stage due to the short time span since its initial report in 2004, a focused review on this topic is timely and necessary. In this feature review, we first summarize the results from toxicity studies of graphene and its derivatives. Although literature reports have mixed findings, we emphasize that the key question is not how toxic graphene itself is, but how to modify and functionalize it and its derivatives so that they do not exhibit acute/chronic toxicity, can be cleared from the body over time, and thereby can be best used for biomedical applications. We then discuss in detail the exploration of graphene-based nanomaterials for tissue engineering, molecular imaging, and drug/gene delivery applications. The future of graphene-based nanomaterials in biomedicine looks brighter than ever, and it is expected that they will find a wide range of biomedical applications with future research effort and interdisciplinary collaboration.     

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.     

Designer,Programmable DNA-peptide hybrid materials with emergent properties to probe and modulate biological systems

The chemistry of DNA endows it with certain functional properties that facilitate the generation of self-assembled nanostructures, offering precise control over their geometry and morphology, that can be exploited for advanced biological applications. Despite the structural promise of these materials, their applications are limited owing to lack of functional capability to interact favourably with biological systems, which has been achieved by functional proteins or peptides. Herein, we outline a strategy for functionalizing DNA structures with short-peptides, leading to the formation of DNA-peptide hybrid materials. This proposition offers the opportunity to leverage the unique advantages of each of these bio-molecules, that have far reaching emergent properties in terms of better cellular interactions and uptake, better stability in biological media, an acceptable and programmable immune response and high bioactive molecule loading capacities. We discuss the synthetic strategies for the formation of these materials, namely, solid-phase functionalization and solution-coupling functionalization. We then proceed to highlight selected biological applications of these materials in the domains of cell instruction & molecular recognition, gene delivery, drug delivery and bone & tissue regeneration. We conclude with discussions shedding light on the challenges that these materials pose and offer our insights on future directions of peptide-DNA research for targeted biomedical applications.