Polymers for medical and tissue engineering applications

Recent decades have seen great advancements in medical research into materials, both natural and synthetic, that facilitate the repair and regeneration of compromised tissues through the delivery and support of cells and/or biomolecules. Biocompatible polymeric materials have become the most heavily investigated materials used for such purposes. Naturally‐occurring and synthetic polymers, including their various composites and blends, have been successful in a range of medical applications, proving to be particularly suitable for tissue engineering (TE) approaches. The increasing advances in polymeric biomaterial research combined with the developments in manufacturing techniques have expanded capabilities in tissue engineering and other medical applications of these materials. This review will present an overview of the major classes of polymeric biomaterials, highlight their key properties, advantages, limitations and discuss their applications. © 2014 Society of Chemical Industry     

Review on polyphosphazenes-based materials for bone and skeleton tissue engineering

The skeleton performs motley of functions. Defected bones and metameric loss of bone are often resulted due to innate abnormalities and accidental injuries. An assessment is made on the diversity of chemistry of phosphazene with an inflection on new developments and their importance in tissue engineering. Tissue engineering mostly uses polymers that can biodegrade in porous/permeable scaffolds form for treating damaged tissues and skeleton. Demand of these polymers is increasing as timely substrates for tissue regeneration in contrast to the mostly used polyethylene terephalate, polyorthoesters, and poly(α-amino acids). Polyphosphazenes as biodegradable polymers have great potential for applications of tissue engineering. Due to biodegradability of P–N backbone, vast diversity of structure and high functional density polyphosphazenes provides many advantages for the formation of biologically compatible macromolecules. However, the nature of the side group determines the degradation ability of such polymers. These biodegradable polymers (polyphosphazenes) provide harmless and pH neutral substances because phosphates and ammonia have high buffer capacity. This review article focuses on the biocompatible polyphosphazenes and their utilization as regeneration of tissues, skeleton, and bones with a particular focus on materials that contains only polyphosphazenes, blends of polyphosphazene, and composites made from polyphosphazene.     

Strategies for non‐invasive imaging of polymeric biomaterial in vascular tissue engineering and regenerative medicine using ultrasound and photoacoustic techniques

The ability of new polymeric materials to provide excellent biomechanical properties expanded their potential for biomedical applications enormously. The use of non‐invasive imaging modalities could provide crucial information to monitor the efficacy/effectiveness/efficiency of the new materials employed in ‘regenerative’ approaches, including scaffolds, hydrogels, self‐assembling materials and nanosized structures. The assessment of the morpho‐functional and metabolic changes of treated or implanted tissues, the visualization of sites of drug delivery and the real‐time check of the in vivo efficacy of therapeutics could be achieved by non‐invasive micro‐ and macro‐imaging techniques. The macro‐ and nano‐requirements of these new materials and their behaviour in vivo can be investigated using standard approaches such as computed tomography, MRI and ultrasound techniques and the emerging photoacoustic imaging. This paper presents recent advancements of ultrasonography and the novel photoacoustic technique to monitor the morpho‐functional parameters of synthetic polymeric scaffolds and conduits in experimental models. © 2016 Society of Chemical Industry     

Degradable natural polymer hydrogels for articular cartilage tissue engineering

Articular cartilage has poor ability to heal once damaged. Tissue engineering with scaffolds of polymer hydrogels is promising for cartilage regeneration and repair. Polymer hydrogels composed of highly hydrated crosslinked networks mimic the collagen networks of the cartilage extracellular matrix and thus are employed as inserts at cartilage defects not only to temporarily relieve the pain but also to support chondrocyte proliferation and neocartilage regeneration. The biocompatibility, biofunctionality, mechanical properties, and degradation of the polymer hydrogels are the most important parameters for hydrogel‐based cartilage tissue engineering. Degradable biopolymers with natural origin have been widely used as biomaterials for tissue engineering because of their outstanding biocompatibility, low immunological response, low cytotoxicity, and excellent capability to promote cell adhesion, proliferation, and regeneration of new tissues. This review covers several important natural proteins (collagen, gelatin, fibroin, and fibrin) and polysaccharides (chitosan, hyaluronan, alginate and agarose) widely used as hydrogels for articular cartilage tissue engineering. The mechanical properties, structures, modification, and structure–performance relationship of these hydrogels are discussed since the chemical structures and physical properties dictate the in vivo performance and applications of polymer hydrogels for articular cartilage regeneration and repair. © 2012 Society of Chemical Industry     

Biodegradable polymers applied in tissue engineering research: a review

Typical applications and research areas of polymeric biomaterials include tissue replacement, tissue augmentation, tissue support, and drug delivery. In many cases the body needs only the temporary presence of a device/biomaterial, in which instance biodegradable and certain partially biodegradable polymeric materials are better alternatives than biostable ones. Recent treatment concepts based on scaffold‐based tissue engineering principles differ from standard tissue replacement and drug therapies as the engineered tissue aims not only to repair but also regenerate the target tissue. Cells have been cultured outside the body for many years; however, it has only recently become possible for scientists and engineers to grow complex three‐dimensional tissue grafts to meet clinical needs. New generations of scaffolds based on synthetic and natural polymers are being developed and evaluated at a rapid pace, aimed at mimicking the structural characteristics of natural extracellular matrix. This review focuses on scaffolds made of more recently developed synthetic polymers for tissue engineering applications. Currently, the design and fabrication of biodegradable synthetic scaffolds is driven by four material categories: (i) common clinically established polymers, including polyglycolide, polylactides, polycaprolactone; (ii) novel di‐ and tri‐block polymers; (iii) newly synthesized or studied polymeric biomaterials, such as polyorthoester, polyanhydrides, polyhydroxyalkanoate, polypyrroles, poly(ether ester amide)s, elastic shape‐memory polymers; and (iv) biomimetic materials, supramolecular polymers formed by self‐assembly, and matrices presenting distinctive or a variety of biochemical cues. This paper aims to review the latest developments from a scaffold material perspective, mainly pertaining to categories (ii) and (iii) listed above. Copyright © 2006 Society of Chemical Industry     

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     

Oxygen‐releasing biomaterials for tissue engineering

Due to the increasing demand to generate thick and vascularized tissue‐engineered constructs, novel strategies are currently being developed. An emerging example is the generation of oxygen‐releasing biomaterials to tackle mass transport and diffusion limitations within engineered tissue constructs. Biomaterials containing oxygen‐releasing molecules can be fabricated in various forms, such as hybrid thin films, microparticles or three dimensional scaffolds. In this perspective, we summarize various oxygen‐releasing reagents and their potential applications in regenerative engineering. Moreover, we review the main approaches for fabricating oxygen‐releasing biomaterials for a range of tissue engineering applications. © 2013 Society of Chemical Industry     

Halloysite clay nanotube in regenerative medicine for tissue and wound healing

The vital necessity of effective treatment at damaged tissue or wound site has resulted in emerging tissue engineering and regenerative medicine. Tissue engineering has been introduced as an alternative approach for common available therapeutic strategies in the terms of restoring deformed tissue structure and its functionality via the developing of new bio-scaffold. Designed three-dimensional (3D) scaffolds, alone or in combination with bioactive agents, should be able to stimulate and accelerate the development of engineered tissues and provide proper mechanical support during in-vivo implantation and later regeneration process. To cover it up, a series of new bio-structures with higher mechanical strength were designed through the combination of halloysite nanotubes (HNTs) into 3D bio-polymeric networks. HNTs clay mineral with its unique rod-like structure and distinctive chemical surface features, exhibits excellent biocompatibility and biosafety for doping into regenerative scaffolds to enhance their mechanical stiffness and biological performance. In this paper, the ongoing procedures of bone/cartilage tissue engineering and wound healing strategies focusing on the designing of 3D-HNTs bio-composites and their multi-cellular interactions in-vitro and in-vivo preclinical studies are reviewed. Furthermore, the challenges and prospects of 3D-HNTs and HNTs-based functional bio-devices for regenerative medicine are also discussed.     

Bioreactors for heart valve tissue engineering: a review

Bioreactors have great potential in the successful development of tissue‐engineered heart valve replacements, both at the research stage and in commercial platforms. Their ability to mimick the chemical and physiological conditions of the body has allowed researchers to study in vitro cellular responses, and this has helped in the fabrication of better and more efficient tissues in vivo. Use of different bioreactors, such as, rotating, dynamic flexure, cyclic stretch and pulsatile bioreactors, in tissue engineering of heart valves has been widely investigated. However, this research is still at its early stage, and many critical issues need to be resolved to make tissue engineered heart valves sufficiently reliable for clinical applications. In the following article, after a brief introduction to the structure and role of heart valves, the efforts of tissue engineers in designing heart valves using different bioreactors is described. © 2015 Society of Chemical Industry     

Advanced graphene ceramics and their future in bone regenerative engineering

The outstanding properties of graphene materials rely on an exceptional two-dimensional honeycombed lattice. The lattice allows for electrical, thermal, and mechanical reinforcement effects when applied to the ceramic matrix. The biocompatibility of the material allows for providing multifunctional bioceramics applications. However, the potential of graphene lies in its ability to be homogenously distributed as part of a ceramic matrix. Therefore, appropriate processing techniques are important for attaining desired graphene ceramic properties applicable for regenerative biomedical purposes. This article provides an inclusive review of the current knowledge of advanced graphene-based ceramics for bone regenerative engineering. In this review, the opportunities and challenges in utilizing graphene materials in combination with ceramics suitable for applications in load-bearing bone defects are discussed.     

Novel polyurethane‐based thermosensitive hydrogels as drug release and tissue engineering platforms: design and in vitro characterization

Poloxamer P407 (P407) is a Food and Drug Administration approved triblock copolymer; its hydrogels show fast dissolution in aqueous environment and weak mechanical strength, limiting their in vivo application. In this work, an amphiphilic poly(ether urethane) (NHP407) was synthesized from P407, an aliphatic diisocyanate (1,6‐hexanediisocyanate) and an amino acid derived diol (N‐Boc serinol). NHP407 solutions in water‐based media were able to form biocompatible injectable thermosensitive hydrogels with a lower critical gelation temperature behavior, having lower critical gelation concentration (6% w/v versus 18% w/v), superior gel strength (G′ at 37 °C about 40 000 Pa versus 10 000 Pa), faster gelation kinetics (<5 min versus 15–30 min) and higher stability in physiological conditions (28 days versus 5 days) compared to P407 hydrogels. Gel strength and PBS absorption at 37 °C increased whereas dissolution rate (in phosphate‐buffered saline (PBS) at 37 °C) and permeability to nutrients (studied using fluorescein isothiocyanate–dextran model molecule) decreased as a function of NHP407 hydrogel concentration from 10% to 20% w/v. By varying the concentration, NHP407 hydrogels were thus prepared with different properties which could suit specific applications, such as in situ drug/cell delivery or bioprinting of scaffolds. Moreover, deprotected amino groups in NHP407 could be exploited for the grafting of bioactive molecules obtaining biomimetic hydrogels. © 2016 Society of Chemical Industry     

Thermoresponsive and acid-cleavable amphiphilic copolymer micelles for controlled drug delivery

Thermoresponsive and acid-cleavable amphiphilic block copolymers poly(N-isopropylacrylamide)-acetal-poly(4-substituted-ε-caprolactones) (PNiPAAm-a-PXCLs) containing an acidic-cleavable acetal linkage at the junction between the temperature-sensitive hydrophilic PNiPAAm and the degradable hydrophobic block PXCL were synthesized through ring-opening polymerization and electrophilic addition reactions. These polymer solutions showed reversible changes in optical properties and a lower critical solution temperature in the range of 32.0–46.4°C. The copolymers formed micelles in aqueous solution with critical micelle concentrations in the range of 0.83–15.95?mg?L^?1 had hydrodynamic sizes of <200?nm and were spherical. Under the combined stimulation of temperature and pH, the micellar nanoparticles could be dissociated; the loaded molecules could be released from the assemblies more efficiently than that under only one stimulus or without stimulus. In addition, the nanoparticles exhibited low toxicity against human cervical cancer (HeLa) cells at concentrations ≤1000?µg?mL^?1. Doxorubicin-loaded PNiPAAm₁₁-a-PCL₂₈ micelles also effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration (IC₅₀) of 1.60?µg?mL^?1.     

组织工程用水凝胶制备方法研究进展

高分子水凝胶作为-类重要的生物材料被广泛应用于生物医药和组织工程领域.本文综述了基于化学交联和物理交联的有关组织工程用水凝胶的设计方法,重点介绍了通过自由基共聚、结构互补基团间的化学反应、高能辐射和酶交联的化学交联型水凝胶以及通过离子间的相互作用,结晶作用、氢键及疏水性相互作用形成的物理交联型水凝胶的研究进展,对比了各种交联机制的优缺点,并对水凝胶在组织工程领域中的进-步应用进行了展望.     

Bio‐inspired materials for biosensing and tissue engineering

This review gives an overview of the research presented in the lecture by Professor Molly Stevens given on the occasion of the 2010 Polymer International‐IUPAC award for creativity in polymer science. Herein we describe some highlights of our biomaterials‐based approaches in the fields of regenerative medicine and biosensing. We have developed a range of polymeric and inorganic materials for use in tissue engineering scaffolds as well as for elucidating the impact of various materials‐based cues on cell behaviour and tissue formation. Specific examples in the field of bone repair are outlined. Furthermore, recent achievements in the creation of sensitive, simple and robust assays for enzyme detection are presented. Our approaches in this field are based on the combination of various nanoparticles with designer polypeptides to provide quantitative colorimetric read‐outs where a specific active enzyme is present. These enzyme assays are likely to be useful for portable point‐of‐care diagnoses of a range of diseases with significant global impact. Copyright © 2012 Society of Chemical Industry     

Electrospun polycaprolactone scaffolds for tissue engineering: a review

Polycaprolactone is a biodegradable and biocompatible polyester which has a wide range of applications in tissue engineering. Electrospinning, the versatile technique, used for the fabrication of fibrous scaffolds, which is widely used in tissue engineering, due to the ability of fabrication of nano/micro-scale fiber scaffolds. Polycaprolactone nanofiber scaffolds are widely used in tissue engineering and drug delivery. Polycaprolactone can be used in a wide variety of scaffolds construction. In this review, we will discuss the recent advances in the electrospinning of polycaprolactone nanofiber scaffolds in bone, cardiovascular, nerve, and skin tissue engineering.     

Unleashing the potential of supercritical fluids for polymer processing in tissue engineering and regenerative medicine

One of the major scientific challenges that tissue engineering and regenerative medicine (TERM) faces to move from benchtop to bedside regards biomaterials development, despite the latest advances in polymer processing technologies.A variety of scaffolds processing techniques have been developed and include solvent casting and particles leaching, compression molding and particle leaching, thermally induced phase separation, rapid prototyping, among others. Supercritical fluids appear as an interesting alternative to the conventional methods for processing biopolymers as they do not require the use of large amounts of organic solvents and the processes can be conducted at mild temperatures. However, this processing technique has only recently started to receive more attention from researchers. Different processing methods based on the use of supercritical carbon dioxide have been proposed for the creation of novel architectures based on natural and synthetic polymers and these will be unleashed in this paper.     

Albumin-based biomaterial for lung tissue engineering applications

The role of albumin-based biomaterials in tissue engineering (TE) cannot be overemphasized. The authors review the role of albumin in lungs scaffold grafting, which promotes cell seeding. Albumin grafted on decellularized lungs scaffold is presented as a great support material for cell-tissue interaction as well as for ease in attachment, growth, and differentiation when seeded with different types of cells. Albumin scaffold fabrication from different sources is a promising approach that may facilitate medical treatments from bench-to-bed, although the role of this scaffold in lungs surfactant proteins regeneration and binding needs to be fully elucidated.     

Photopolymerization of biomaterials: issues and potentialities in drug delivery,tissue engineering,and cell encapsulation applications

Photopolymerization is a widely explored technology that has recently been recognized to have also great potentialities in the biomedical field. This paper aims to provide a general overview of this technology by briefly describing materials and methods used to produce linear or crosslinked polymer networks for drug delivery, tissue engineering and cell encapsulation. In addition, potentialities and areas of investigation that are not fully explored but that could provide solutions for better control over the technology when applied to the biomedical field will be indicated as well. Copyright © 2006 Society of Chemical Industry     

PVA-based hydrogels for tissue engineering: A review

Poly (vinyl alcohol) (PVA) is a hydrophilic polymer with excellent biocompatibility and has been applied in various biomedical areas due to its favorable properties. PVA-based hydrogels have been recognized as promising biomaterials and suitable candidates for tissue engineering applications and can be manipulated to act various critical roles. However, due to some disadvantages (i.e., lack of cell-adhesive property), they needs further modification for desired and targeted applications. This review highlights recent progress in the design and fabrication of PVA-based hydrogels, including crosslinking and processing techniques. Finally, major challenges and future perspectives in tissue engineering are briefly discussed.     

Polymeric scaffolds for cardiac tissue engineering: requirements and fabrication technologies

Cardiac tissue engineering (TE) is an emerging field, whose main goal is the development of innovative strategies for the treatment of heart diseases, with the aim of overcoming the drawbacks of traditional therapies. One of these strategies involves the implantation of three‐dimensional matrices (scaffolds) capable of supporting tissue formation. Scaffolds designed and fabricated for such application should meet several requirements, concerning both the scaffold‐forming materials and the properties of the scaffold itself. A scaffold for cardiac TE should be biocompatible and biodegradable, mimic the properties of the native cardiac tissue, provide a mechanical support to the regenerating heart and possess an interconnected porous structure to favour cell migration, nutrient and oxygen diffusion, and waste removal. Moreover, the mimesis of myocardium characteristic anisotropy is attracting increasing interest to provide engineered constructs with the possibility to be structurally and mechanically integrated in native tissue. Several conventional and non‐conventional fabrication techniques have been explored in the literature to produce polymeric scaffolds meeting all these requirements. This review describes these techniques, with a focus on their advantages and disadvantages, and their flexibility, with the final goal of providing the reader with the primal knowledge necessary to develop an effective strategy in cardiac TE. © 2013 Society of Chemical Industry