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.     

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     

Protein encapsulated in electrospun nanofibrous scaffolds for tissue engineering applications

The main purpose of tissue engineering is the preparation of fibrous scaffolds with similar structural and biochemical cues to the extracellular matrix in order to provide a substrate to support the cells. Controlled release of bioactive agents such as growth factors from the fibrous scaffolds improves cell behavior on the scaffolds and accelerates tissue regeneration. In this study, nanofibrous scaffolds were fabricated from biocompatible and biodegradable poly(lactic‐co‐glycolic acid) through the electrospinning technique. Nanofibers with a core–sheath structure encapsulating bovine serum albumin (BSA) as a model protein for hydrophilic bioactive agents were prepared through emulsion electrospinning. The morphology of the nanofibers was evaluated by field‐emission scanning electron microscopy and the core–sheath structure of the emulsion electrospun nanofibers was observed by transmission electron microscopy. The results of the mechanical properties and X‐ray diffraction are reported. The scaffolds demonstrated a sustained release profile of BSA. Biocompatibility of the scaffolds was evaluated using the MTT (3(4,5‐ dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay for NIH‐3T3 fibroblast cells. The results indicated desirable biocompatibility of the scaffolds with the capability of encapsulation and controlled release of the protein, which can serve as tissue engineering scaffolds. © 2013 Society of Chemical Industry     

Numerical simulations of bioextruded polymer scaffolds for tissue engineering applications

Scaffolds provide a temporary mechanical and vascular support for tissue regeneration while shaping the in‐growth tissues. These scaffolds must be biocompatible, biodegradable, enclose appropriate porosity, pore structure and pore distribution, and have optimal structural and vascular performance, with both surface and structural compatibility. Surface compatibility means a chemical, biological and physical suitability to the host tissue. Structural compatibility corresponds to an optimal adaptation to the mechanical behaviour of the host tissue. Recent advances in the design of tissue engineering scaffolds are increasingly relying on computer‐aided design modelling and numerical simulations. The design of optimized scaffolds based on fundamental knowledge of their macro microstructure is a relevant topic of research. This research work presents a comparison between experimental compressive data and numerical simulations of bioextruded polymer scaffolds with different pore sizes for the elastic and plastic domain. Constitutive behaviour models of cellular structures are used in numerical simulations to compare numerical data with the experimental compressive data. Vascular simulation is also used in the design process of the extrusion‐based scaffolds in order to define an optimized scaffold design. © 2013 Society of Chemical Industry     

碳纤维增强聚合物组织工程支架的制备及表征

以碳纤维（CF）作为增强材料,将CF有序排列于聚乳酸羟基乙酸（PLGA）多孔结构中,制备性能优良的CF/PLGA复合支架,并对其力学性能及细胞生物学性能进行表征.对增强体CF进行有序排列以提高支架的力学性能,扫描电子显微镜（SEM）观察CF/PLGA复合支架的微观形貌,可以看出CF在聚合物基体内部是呈有序结构并且二者结合情况良好.为了提高CF的生物相容性,利用对氨基苯甲酸对CF进行表面修饰,细胞生长在支架上的SEM照片反映了成纤维细胞对PLGA及CF/PLGA复合支架的黏附性能良好;通过细胞毒性测试,发现表面修饰的CF对细胞的生长没有负面作用,且在一定程度上促进了细胞的生长.研究结果表明,制备的CF/PLGA支架具有良好的力学性能和生物相容性,在骨组织工程支架的应用中具有一定的潜力.     

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.     

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     

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.     

组织工程多孔支架微管内流场数值模拟

骨支架内部微管结构对营养液和细胞在其内部的流动有着非常重要的影响。利用流体计算软件Fluent对不同尺寸的人工骨微管结构内部营养液和细胞的流动状况进行了数值模拟,得到了不同几何结构骨支架内部流场的速度和压力分布图。结果表明,从进口到出口,主管道内流体流速随管道的深入不断减小。上端浮克曼管中流体流速比下端浮克曼管中流体流速高,但是比同一高度主管道内流体流速低。哈佛氏管与第一行浮克曼管交叉处下端的哈佛氏管内存在流动缓慢区,第三行浮克曼管与哈佛氏管交叉处开始,流体速度不断增大。随浮克曼管长度的增加,上端哈佛氏管中流体流动的缓慢区减小;随浮克曼管直径的增加,浮克曼管中的流速有所增加,并且各微管中流体的流速更为均匀;随浮克曼管与主管道夹角的增加,骨支架各微管内流体流速更加均匀,利于细胞和营养液在各管道的输运。本数值模拟范围内,最佳骨支架结构参数为浮克曼管长度3mm,直径0.6mm,浮克曼管与主管道夹角90°。     

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     

Thermal processing of a degradable carboxylic acid-functionalized polycarbonate into scaffolds for tissue engineering

Degradable polymers are often desirable for the fabrication of medical implants, but thermal processing of these polymers is a challenge. We describe here how these problems can be addressed by discussing the extrusion of fibers and injection molding of bone pins from a hydrolytically degradable tyrosine-derived polycarbonate. Our initial attempts produced fibers and pins with bubbles, voids, and discoloration and resulted in the formation of large polymer plugs that seized screws and blocked extruder dies. The material and process parameters that contribute to these issues were investigated by studying the physical and chemical changes that occur during processing. Differential scanning calorimetry and thermogravimetric analysis combined with IR analysis showed that residual moisture and solvents in conjunction with heat cause degradation and crosslinking as indicated by gel permeation chromatography. Rheology and melt flow index measurements were useful in characterizing the extent of dependence of polymer viscosity on temperature and molecular weight. With these insights, we could process our polymer into fibers and rods by controlling residual moisture, time, and temperature and by adjusting processing parameters in real time. The systematic approach described here is applicable to other degradable polymers that are difficult to process.     

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     

Incorporation of inorganic bioceramics into electrospun scaffolds for tissue engineering applications: A review

Today, the integration of medical and engineering principles for producing biological replacements has attracted much attention. Tissue engineering is an interdisciplinary field introduced for recovery, preservation, and improvement of tissues' function. During the process of reproduction, scaffolds with the support of cells and biological materials and growth factors underlie the effective regeneration of the target tissue. Among the numerous methods, the electrospinning method has the great ability to mimic the extracellular matrix by creating a network of polymer fibers with a high surface area at the nanoscale in order to provide more binding sites for cells. Considering the capabilities and limitations of different polymers, the use of ceramics as a reinforcement phase is a promising approach. Over the past few decades, electrospun scaffolds have been developed by adding different ceramics in terms of their nature, bioinert, bioactive, and biodegradable properties. The main results are related to enhancing the mechanical properties and biological behavior of the polymeric scaffolds after the incorporation of ceramics. Enhanced hydrophilicity, antibacterial and antioxidant properties are other aspects caused by chemical interactions of ceramics and polymers. In this review, the effect of adding inorganic ceramic structures incorporated into polymeric electrospun scaffolds is discussed by highlighting the most recent studies in tissue engineering applications.     

An assessment of biopolymer‐ and synthetic polymer‐based scaffolds for bone and vascular tissue engineering

The promise of tissue engineering is the combination of a scaffold with cells to initiate the regeneration of tissues or organs. Engineering of scaffolds is critical for success and tailoring of polymer properties is essential for their good performance. Many different materials of natural and synthetic origins have been investigated, but the challenge is to find those that have the right mix of mechanical performance, biodegradability and biocompatibility for biological applications. This article reviews key polymeric properties for bone and vascular scaffold eligibility with focus on biopolymers, synthetic polymers and their blends. The limitations of these polymeric systems and ways and means to improve scaffold performance specifically for bone and vascular tissue engineering are discussed. © 2013 Society of Chemical Industry     

骨组织工程中的碳纤维材料

归纳了聚合物支架材料在提高其力学性能方面的一些研究工作,并综述了碳纤维材料在骨组织工程上应用的进展.分析表明,骨组织工程是修复骨缺损的有效方法之一,而碳纤维材料的结构性能优势使其成为提高组织工程支架性能的首选材料之一.在提高聚合物支架力学性能的同时,进一步提高材料的生物活性和促进骨的修复是目前研究的重点和难点.指出可通过对碳纤维材料的改性、有序排列等手段来进一步提高碳纤维材料的作用.     

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     

Silicon-doped hydroxyapatite prepared by a thermal technique for hard tissue engineering applications

Hydroxyapatite (HA, Ca₅(PO₄)₃OH) has been extensively used for bone implantation due to its similarity to the mineral component of bone, which makes it strongly osteoconductive. However, HA has low resorbability, and it is difficult to replace by a newly regenerated bone. Si doping can enhance the resorbability of HA by modifying its crystal structure. Here, we developed a simple thermal technique for preparing Si-doped HA from silica (SiO₂) and HA precursors, both of which are inexpensive and commercially available. This method included the physical binding of SiO₂ and HA particles, followed by pressing and sintering the mixture at an elevated temperature, which enhanced the atomic diffusion of Si into HA unit cells. We also evaluated the simulated body fluid (SBF) activity of the Si-doped HA prepared by this technique and showed that it significantly had higher resorbability and mineralizing potential compared to the pure HA. Our experimental design including, the individual precipitation and resorption assays enabled us to explain the mechanism behind the improved activity of Si-doped HA in SBF. This was attributed to the formation of new phases, such as β-tricalcium phosphate (β-TCP) and calcium silicate (Ca₂SiO₄) with higher solubility than HA on the SiO₂-contating HA during the sintering stage. This can provide some guidelines for designing new calcium phosphate-based materials for hard tissue engineering applications.     

A comprehensive review on the preparation and application of calcium hydroxyapatite: A special focus on atomic doping methods for bone tissue engineering

Hydroxyapatite (HAP) has been considered to be one of the most preferred scaffold materials among many in the last decade for the bone tissue engineering. Be it prosthetic implants, scaffolds or artificial bone cement, hydroxyapatite has received highest attraction among all due to its chemical and physical properties similar to that of human bone. Although it can be used in the bone tissue engineering as the original composition; for enhancing its different properties relevant to in vivo applications, the calcium in HAP may also be replaced by other atomic dopants depending on usage. Here, we review various HAP coating agents and methods, their merits and demerits. We also review various HAP doping materials, including both cationic as well as anionic materials. We discuss the effects and usage of substitution of hydroxyapatite and their subsequent usage in both bone tissue engineering and maxillofacial surgeries. We consider various research articles published in recent times to accomplish detailed discussion on the subject.