Biodegradable polymer blends: miscibility,physicochemical properties and biological response of scaffolds

This review provides an overview of synthetic biodegradable polymer blends prepared for tissue engineering applications and aims at establishing structure‐physicochemical‐biological properties relationships. The characteristics of blends consisting of semi‐crystalline/semi‐crystalline and semi‐crystalline/amorphous polymers are presented. Their biological properties such as degradability and biocompatibility and their biological performance as scaffolds in relation to cell adhesion, proliferation, infiltration, morphology and type are discussed. From available data, it can be deduced that miscibility influences physicochemical properties of the corresponding biodegradable polymeric blend scaffold, which in turn impacts on biological response. Immiscibility in polymer blends generally translates into good cell adhesion and proliferation. However, better cellular infiltration has been noted in compatible blends compared to immiscible blends. Factors such as crystallinity versus amorphous character, chirality, surface properties, degradation rate/products, mechanical properties and scaffold fabrication techniques are shown to have a major bearing on cell growth. © 2015 Society of Chemical Industry     

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     

Plasma polymerization‐modified bacterial polyhydroxybutyrate nanofibrillar scaffolds

The design and the development of novel scaffold materials for tissue engineering have attracted much interest in recent years. Especially, the prepared nanofibrillar scaffold materials from biocompatible and biodegradable polymers by electrospinning are promising materials to be used in biomedical applications. In this study, we propose to produce low‐cost and cell‐friendly bacterial electrospun PHB polymeric scaffolds by using Alcaligenes eutrophus DSM 545 strain to PHB production. The produced PHB was characterized by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). Nanofibrous scaffolds were fabricated via electrospinning method that has a fiber diameter approximately 700–800 nm. To investigate cell attachment, cell growth, and antioxidant enzyme activity on positively and negatively charged PHB scaffold, PHB surface was modified by plasma polymerization technique using polyethylene glycol (PEG) and ethylenediamine (EDA). According to the results of superoxide dismutase (SOD) activity study, PEG‐modified nanofibrillar scaffolds indicated more cellular resistance against oxidative stress compared to the EDA modification. As can be seen in cell proliferation results, EDA modification enhanced the cell proliferation more than PEG modification, while PEG modification is better as compared with nonmodified scaffolds. In general, through plasma polymerization technique, surface modified nanofibrillar structures are effective substrates for cell attachment and outgrowth. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Additive Manufacturing of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Poly(D,L-lactide-co-glycolide) Biphasic Scaffolds for Bone Tissue Regeneration

Polyhydroxyalkanoates are biopolyesters whose biocompatibility, biodegradability, environmental sustainability, processing versatility, and mechanical properties make them unique scaffolding polymer candidates for tissue engineering. The development of innovative biomaterials suitable for advanced Additive Manufacturing (AM) offers new opportunities for the fabrication of customizable tissue engineering scaffolds. In particular, the blending of polymers represents a useful strategy to develop AM scaffolding materials tailored to bone tissue engineering. In this study, scaffolds from polymeric blends consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(D,L-lactide-co-glycolide) (PLGA) were fabricated employing a solution-extrusion AM technique, referred to as Computer-Aided Wet-Spinning (CAWS). The scaffold fibers were constituted by a biphasic system composed of a continuous PHBV matrix and a dispersed PLGA phase which established a microfibrillar morphology. The influence of the blend composition on the scaffold morphological, physicochemical, and biological properties was demonstrated by means of different characterization techniques. In particular, increasing the content of PLGA in the starting solution resulted in an increase in the pore size, the wettability, and the thermal stability of the scaffolds. Overall, in vitro biological experiments indicated the suitability of the scaffolds to support murine preosteoblast cell colonization and differentiation towards an osteoblastic phenotype, highlighting higher proliferation for scaffolds richer in PLGA.     

Investigating the effect of PGA on physical and mechanical properties of electrospun PCL/PGA blend nanofibers

In the field of tissue engineering there is always a need for new engineered polymeric biomaterials which have ideal properties and functional customization. Unfortunately the demands for many biomedical applications need a set of properties that no polymers can fulfill. One method to satisfy these demands and providing desirable new biomaterials is by mixing two or more polymers. In this work, random nanofibrous blends of poly (ε‐caprolactone) (PCL) and polyglycolic acid (PGA) with various PCL/PGA compositions (100/0, 80/20, 65/35, 50/50, and 0/100) were fabricated by electrospinning method and characterized for soft‐tissue engineering applications. Physical, chemical, thermal, and mechanical properties of PCL/PGA blend nanofibers were measured by scanning electron microscopy (SEM), porosimetry, contact angle measurement, water uptake, attenuated total reflectance Fourier transform‐infrared spectroscopy (ATR‐FT‐IR), X‐ray diffraction (XRD), differential scanning calorimetric (DSC), dynamic mechanical thermal analysis (DMTA), and tensile measurements. Morphological characterization showed that the addition of PGA to PCL results in an increase in the average diameter of the nanofibers. According to these results, when the amount of PGA in the blend solution increased, the hydrophilicity and water uptake of the nanofibrous scaffolds increased concurrently, approaching those of PGA nanofibers. Differential scanning calorimetric studies showed that the PCL and PGA were miscible in the nanofibrous structure and the mechanical characterization under dry conditions showed that increasing PGA content results in a tremendous increase in the mechanical properties. In conclusion, the random nanofibrous PCL/PGA scaffold used in this study constitutes a promising material for soft‐tissue engineering. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Development of novel porous nasal scaffold using injection molding

Porous scaffolds fabricated from biodegradable polymers have been widely used and play a vital role in tissue engineering and in situ tissue reconstruction. This study presents a novel fabrication technique involving injection molding and conventional particulate leaching (IM/PL) to obtain the L‐shaped nasal scaffold for rhinoplasty. The results indicate that the porous nasal scaffold made by the IM/PL method shows the acceptable biocompatibility and degradation. The nasal scaffold may degrade well after surgery and the cartilage tissue may grow well in it. This IM/PL technique may replace the traditional artificial silicone filler and reduce the surgery cost. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers     

Composite scaffolds for cartilage tissue engineering based on natural polymers of bacterial origin,thermoplastic poly(3‐hydroxybutyrate) and micro‐fibrillated bacterial cellulose

Cartilage tissue engineering is an emerging therapeutic strategy that aims to regenerate damaged cartilage caused by disease, trauma, ageing or developmental disorder. Since cartilage lacks regenerative capabilities, it is essential to develop approaches that deliver the appropriate cells, biomaterials and signalling factors to the defect site. Materials and fabrication technologies are therefore critically important for cartilage tissue engineering in designing temporary, artificial extracellular matrices (scaffolds), which support 3D cartilage formation. Hence, this work aimed to investigate the use of poly(3‐hydroxybutyrate)/microfibrillated bacterial cellulose (P(3HB)/MFC) composites as 3D‐scaffolds for potential application in cartilage tissue engineering. The compression moulding/particulate leaching technique employed in the study resulted in good dispersion and a strong adhesion between the MFC and the P(3HB) matrix. Furthermore, the composite scaffold produced displayed better mechanical properties than the neat P(3HB) scaffold. On addition of 10, 20, 30 and 40 wt% MFC to the P(3HB) matrix, the compressive modulus was found to have increased by 35%, 37%, 64% and 124%, while the compression yield strength increased by 95%, 97%, 98% and 102% respectively with respect to neat P(3HB). Both cell attachment and proliferation were found to be optimal on the polymer‐based 3D composite scaffolds produced, indicating a non‐toxic and highly compatible surface for the adhesion and proliferation of mouse chondrogenic ATDC5 cells. The large pores sizes (60 ‐ 83 µm) in the 3D scaffold allowed infiltration and migration of ATDC5 cells deep into the porous network of the scaffold material. Overall this work confirmed the potential of P(3HB)/MFC composites as novel materials in cartilage tissue engineering. © 2016 Society of Chemical Industry     

A review on mechanical and In-vitro studies of polymer reinforced bioactive glass-scaffolds and their fabrication techniques

Over the last few decades, extensive research has been carried out in the field of bioactive scaffolds as replacement material in bone-tissue engineering. The scaffolds have been fabricated employing a combination of biodegradable polymers (due to their biocompatibility and adaptive degradation) and bioactive glass (to impart strength and bioactivity). In this review, a detailed study on the mechanical behavior of polymer-bioactive glass scaffold has been conducted, revealing insufficient strength compared to human cortical bone. The impact of ceramic filler content on the in-vitro bioactivity and biodegradability of scaffold have been discussed. Finally, the rationale and approach for fabricating these 3-D scaffolds with well-distributed and interconnected pores have been reviewed.     

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.     

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     

Fabrication of co‐continuous poly(ε‐caprolactone)/polyglycolide blend scaffolds for tissue engineering

The apparent inability of a single biomaterial to meet all the requirements for tissue engineering scaffolds has led to continual research in novel engineered biomaterials. One method to provide new materials and fine‐tune their properties is via mixing materials. In this study, a biodegradable powder blend of poly(ε‐caprolactone) (PCL), polyglycolide (PGA), and poly(ethylene oxide) (PEO) was prepared and three‐dimensional interconnected porous PCL/PGA scaffolds were fabricated by combining cryomilling and compression molding/polymer leaching techniques. The resultant porous scaffolds exhibited co‐continuous morphologies with ～50% porosity. Mean pore sizes of 24 and 56 μm were achieved by varying milling time. The scaffolds displayed high mechanical properties and water uptake, in addition to a remarkably fast degradation rate. The results demonstrate the potential of this fabrication approach to obtain PCL/PGA blend scaffolds with interconnected porosity. In general, these results provide significant insight into an approach that will lead to the development of new composites and blends in scaffold manufacturing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42471.     

Wet‐spinning of biomedical polymers: from single‐fibre production to additive manufacturing of three‐dimensional scaffolds

Wet‐spinning of polymeric materials has been widely investigated for various biomedical applications, such as extracorporeal blood treatment, controlled drug release and tissue engineering. This review is aimed at summarizing and assessing current advances in wet‐spinning of biomedical polymers to manufacture single fibres and three‐dimensional scaffolds, as well as their functionalization through loading with bioactive agents. The theoretical principles and the main technological aspects of fibre production by wet‐spinning on either a laboratory or an industrial scale are outlined. The non‐solvent‐induced phase inversion determining polymer coagulation during the wet‐spinning process is discussed by highlighting its influence on the resulting fibre morphology and how it can be exploited to induce a nano/microporosity in the solidified polymeric matrix. The versatility of wet‐spinning in material selection, bioactive agent loading and fibre morphology tuning is underlined through an overview of significant literature reporting on the processing of various naturally derived and synthetic polymers. A special focus is given to cutting‐edge advancements in the application of additive manufacturing principles to wet‐spinning for enhanced control and reproducibility of three‐dimensional polymeric scaffold morphology at different scale levels (i.e. macrostructural to micro/nanostructural features). © 2017 Society of Chemical Industry     

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     

Chitin scaffolds in tissue engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.     

Silk fibroin‐chondroitin sulfate‐alginate porous scaffolds: Structural properties and in vitro studies

The development of porous biodegradable scaffolds is of great interest in tissue engineering. In this regard, exploration of novel biocompatible materials is needed. Silk fibroin‐chondroitin sulfate‐sodium alginate (SF‐CHS‐SA) porous hybrid scaffolds were successfully prepared via lyophilization method and crosslinked by 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide‐ethanol treatment. According to the scanning electron microscopy studies, mean pore diameters of the scaffolds were in the range of 60–187 μm. The porosity percentage of the scaffold with SF‐CHS‐SA ratio of 70 : 15 : 15 (w/w/w %) was 92.4 ± 3%. Attenuated total reflectance Fourier transform infrared spectroscopy, X‐ray diffraction, and differential scanning calorimetry results confirmed the transition from amorphous random coil to crystalline β‐sheet in treated SF‐CHS‐SA scaffold. Compressive modulus was significantly improved in hybrid scaffold with SF‐CHS‐SA ratio of 70 : 15 : 15 (3.35 ± 0.15 MPa). Cytotoxicity assay showed that the scaffolds have no toxic effects on chondrocytes. Attachment of chondrocytes was much more improved within the SF‐CHS‐SA hybrid scaffold. Real‐time polymerase chain reaction analyses showed a significant increase in gene expression of collagen type II, aggrecan, and SOX9 and decrease in gene expression of collagen type I for SF‐CHS‐SA compared with SF scaffold. This novel hybrid scaffold can be a good candidate to be utilized as an efficient scaffold for cartilage tissue engineering. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41048.     

Development of 3D in Vitro Technology for Medical Applications

In the past few years, biomaterials technologies together with significant efforts on developing biology have revolutionized the process of engineered materials. Three dimensional (3D) in vitro technology aims to develop set of tools that are simple, inexpensive, portable and robust that could be commercialized and used in various fields of biomedical sciences such as drug discovery, diagnostic tools, and therapeutic approaches in regenerative medicine. The proliferation of cells in the 3D scaffold needs an oxygen and nutrition supply. 3D scaffold materials should provide such an environment for cells living in close proximity. 3D scaffolds that are able to regenerate or restore tissue and/or organs have begun to revolutionize medicine and biomedical science. Scaffolds have been used to support and promote the regeneration of tissues. Different processing techniques have been developed to design and fabricate three dimensional scaffolds for tissue engineering implants. Throughout the chapters we discuss in this review, we inform the reader about the potential applications of different 3D in vitro systems that can be applied for fabricating a wider range of novel biomaterials for use in tissue engineering.     

肝组织工程材料的研究进展

肝组织工程支架材料是肝组织工程学的重要研究内容，是解决肝脏器官严重短缺的关键。目前用于肝组织工程支架材料的主要有天然生物材料和人工合成生物材料。天然类主要包括生物相容性较好的壳聚糖、海藻酸钠等，但其力学性能和可加工性较差；人工合成材料主要包括优良机械性能和可加工性的聚乙酰内脂、聚乳酸-羟基乙酸共聚物等，但其组织相容性较差。如果能利用修饰或者改性的方法，使天然生物材料和人工高分子聚合物扬长避短，则有可能制造出一类兼有良好的力学性能和细胞相容性的生物材料。     

Biocomposites: Their multifunctionality

During the last decade, tissue engineering has shown a considerable promise in providing more viable alternatives to surgical procedures for harvested tissues, implants and prostheses. Due to the fast development on nano- and biomaterial technologies, it is now possible for doctors to use patients' cells to repair orthopaedic defects such as focal articular cartilage lesions. In order to support the three-dimensional tissue formation, scaffolds made by biocompatible and bioresorbable polymers and composite materials, for providing temporary support of damaged body and cell structures, have been developed recently. Although ceramic and metallic materials have been widely accepted for the development of implants, their non-resorbability and necessity of second surgical operation (like for bone repair), which induce extra pain for the patients, limit their wide applications. The development of different types of biocomposites for biomedical engineering applications is described. These biocomposites include (i) basic biomaterials; (ii) natural fiber-reinforced biocomposites and (iii) nanoparticle-reinforced biocomposites. Their multifunctionality is discussed in terms of the control of mechanical properties, biodegradability and bioresorbability.     

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.