Facile preparation and cytocompatibility of poly(lactic acid)/poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) hybrid fibrous scaffolds

A fibrous scaffold is required to provide three‐dimensional (3D) cell growth microenvironments and appropriate synergistic cell guidance cues. In this study, porous scaffolds with different mass ratio of poly(lactic acid) to poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) (P(3HB‐co‐4HB)) for tissue engineering were prepared by a modified particle leaching method. The effect of the addition of P(3HB‐co‐4HB) on microstructural morphology, compression property, swelling behavior, and enzymatic degradation of hybrid scaffolds was systematically investigated. The results indicated that this method was simple but efficient to prepare highly interconnected biomimetic 3D hybrid scaffolds (PP50/50 and PP33/67) with fibrous pore walls. The cytocompatibility of hybrid scaffolds was evaluated by in vitro culture of mesenchymal stem cells. The cell‐cultured hybrid scaffolds presented a complete 3D porous structure, thus allowing cell proliferation on the surface and infiltration into the inner part of scaffolds. The obtained hybrid scaffolds with pore size ranging from 200 to 450 µm, over 90% porosity, adjustable biodegradability, and water‐uptake capability will be promising for cartilage tissue engineering applications. POLYM. ENG. SCI., 54:2902–2910, 2014. © 2014 Society of Plastics Engineers     

Graphene functionalized decellularized scaffold promotes skin cell proliferation

An increasing number of new strategies for skin tissue engineering have been developed with the potential to mimic the biological properties of native tissue with a high degree of complexity, flexibility, and reproducibility. In this study, decellularized tissue (DT) was prepared from the bovine heart by using chemical treatments. However, the mechanical properties of the DT constructs were poorer than the extra cellular matrix of the skin tissue. To overcome this challenge, hybrid scaffolds of DT and graphene oxide (GO) were developed and the effects of the GO concentration on the morphology, pore size, porosity, mechanical strength, and water uptake capacity of the samples were evaluated. Moreover, the biocompatibility of hybrid scaffolds was studied by Live/Dead staining. The results show that a hybrid scaffold incorporating 3 % graphene oxide improved the mechanical strength and cell viability by ~25 % in comparison to the DT scaffolds. Cell viability results confirmed that the porous scaffolds could support cell adhesion, proliferation, and cell activity for 7 days. This study provides new insight into and opportunities for using graphene-based materials to develop biomimetic constructs for clinical applications.     

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     

Fabrication of porous scaffolds with a controllable microstructure and mechanical properties by porogen fusion technique

Macroporous scaffolds with controllable pore structure and mechanical properties were fabricated by a porogen fusion technique. Biodegradable material poly (d, l-lactide) (PDLLA) was used as the scaffold matrix. The effects of porogen size, PDLLA concentration and hydroxyapatite (HA) content on the scaffold morphology, porosity and mechanical properties were investigated. High porosity (90% and above) and highly interconnected structures were easily obtained and the pore size could be adjusted by varying the porogen size. With the increasing porogen size and PDLLA concentration, the porosity of scaffolds decreases, while its mechanical properties increase. The introduction of HA greatly increases the impact on pore structure, mechanical properties and water absorption ability of scaffolds, while it has comparatively little influence on its porosity under low HA contents. These results show that by adjusting processing parameters, scaffolds could afford a controllable pore size, exhibit suitable pore structure and high porosity, as well as good mechanical properties, and may serve as an excellent substrate for bone tissue engineering.     

A review of bioceramic porous scaffolds for hard tissue applications: Effects of structural features

Tissue engineering has acquired remarkable attention as an alternative strategy to treat and restore bone defects during recent years. A scaffold is a fundamental component for tissue engineering, on which cells attach, proliferate and differentiate to form new desirable functional tissue. The composition, and structural features of scaffolds, including porosity and pore size, play a fundamental role in the success of tissue-engineered construct. This review summarizes the effect of porosity and pore size of bioceramic-based scaffolds on their mechanical properties and biological performances. The focus of this review is on scaffolds with porosities 40% and above. From the mechanical point of view, the degree of porosity is a more important factor than pore size and scaffolds with porosities greater than 40% were more likely to substitute trabecular bones. While for in vitro and in vivo performances, pore size appeared more influential feature and co-existence of macropores and micropores led to better bone formation.     

An applicable electrospinning process for fabricating a mechanically improved nanofiber mat

Engineered polymer scaffolds play an important role in tissue engineering. An ideal scaffold should have good mechanical properties and provide a biologically functional implant site. Considering their large surface area and high porosity, nanofibers have good potential as biomimetic scaffolds. However, the main shortcomings of scaffolds consisting of nanofibers are their mechanical inability to sustain a stress environment for neotissues and shape‐ability to form a variety of shapes and sizes. In this study, we produced design‐based poly (ε‐carprolactone) (PCL) nanofiber mats using an electrospinning method with various auxiliary electrodes and an x‐y moving system. To achieve stable initial solution at a nozzle tip of the electrospinning, various types of auxiliary electrodes were introduced. To characterize the effect of the electrodes in the electric‐field distribution near the nozzle tip, we calculated the electric field concentration factor and compared it with the experimental results. The nanofiber mat produced using the moving x‐y target system demonstrated orthotropic mechanical properties due to the fiber orientation, and human dermal fibroblasts seeded on the structure tended to grow according to nanofiber orientation. POLYM. ENG. SCI., 47:707–712, 2007. © 2007 Society of Plastics Engineers.     

Microwave processing of starch‐based porous structures for tissue engineering scaffolds

A novel microwave (MW) processing technique was used to produce biodegradable scaffolds for tissue engineering from different types of starch‐based polymers. Potato, sweet potato, corn starch, and nonisolated amaranth and quinoa starch were used to produce porous structures. Water and glycerol were used as plasticizers for the different types of starch. Characterization of the pore morphology of the scaffolds was carried out with scanning electron microscopy. Three‐dimensional structures with variable porosity and pore size distribution were obtained with the MW foaming technique. The amount of remaining water in the scaffolds and their corresponding densities showed important variations among the different types of starch. Compressive mechanical properties were assessed by indentation tests, and a strong dependence of the indentation stress on the average pore size was found. Studies in simulated body fluid were used to assess the in vitro bioactivity, degradability, and surface topology evolution in the scaffolds. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1332–1339, 2007     

Characterization of 3D elastic porous polydimethylsiloxane (PDMS) cell scaffolds fabricated by VARTM and particle leaching

In this study, elastic porous polydimethylsiloxane (PDMS) cell scaffolds were fabricated by vacuum‐assisted resin transfer moulding (VARTM) and particle leaching technologies. To control the porous morphology and porosity, different processing parameters, such as compression load, compression time, and NaCl particle size for preparing NaCl preform, were studied. The porous structures of PDMS cell scaffolds were characterized by scanning electron microscopy (SEM). The properties of PDMS cell scaffolds, including porosity, water absorption, interconnectivity, compression modulus, and compression strength were also investigated. The results showed that after the porogen–NaCl particles had been leached, the remaining pores had the sizes of 150–300, 300–450, and 450–600 μm, which matched the sizes of the NaCl particles. The interconnectivity of PDMS cell scaffolds increases with an increase in the size of NaCl particles. It was also found that the smaller the size of the NaCl particles, the higher the porosity and water absorption of PDMS cell scaffolds. The content of residual NaCl in PDMS/NaCl scaffolds reduces under ultrasonic treatment. In addition, PDMS scaffolds with a pore size of 300–450 μm have better mechanical properties compared to those with pore sizes of 150–300 and 450–600 μm. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42909.     

Injection‐molded porous hydroxyapatite/polyamide‐66 scaffold for bone repair and investigations on the experimental conditions

Hydroxyapatite/polyamide‐66 (HA/PA66) composite scaffolds were prepared using injection‐molding technique and also analyzed by means of scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and mechanical testing. Compared with common methods to fabricate scaffolds, this process can fabricate composite scaffolds in a rapid and convenient manner by adjusting the experimental conditions of foaming agent and shot size. The interactions between PA66 and HA particles affect the crystallization behavior of PA66 and the pore structure of scaffolds. HA particles can increase the stiffness of composite scaffolds accompanied by the reduction of impact strength, pore size and porosity. The obtained 40 wt% HA/PA66 composite scaffolds with a pore size ranging from 100–500 μm and a porosity more than 65% can simultaneously meet the requirements of porous structure and mechanical performance. POLYM. ENG. SCI., 54:1003–1012, 2014. © 2013 Society of Plastics Engineers     

Fabrication of PCL/β‐TCP scaffolds by 3D mini‐screw extrusion printing

Scaffolds of polycaprolactone (PCL) and PCL composites reinforced with β‐tricalcium phosphate (β‐TCP) were manufactured aiming potential tissue engineering applications. They were fabricated using a three‐dimensional (3D) mini‐screw extrusion printing, a novel additive manufacturing process, which consists in an extrusion head coupled to a 3D printer based on the Fab@Home equipment. Thermal properties were obtained by differential scanning calorimetry and thermogravimetric analyses. Scaffolds morphology were observed using scanning electron microscopy and computed microtomography; also, reinforcement presence was observed by X‐ray diffraction and the polymer chemical structure by Fourier transform infrared spectroscopy. Mechanical properties under compression were obtained by using a universal testing machine and hydrophilic properties were studied by measuring the contact angle of water drops. Finally, scaffolds with 55% of porosity and a pore size of 450 μm have shown promising mechanical properties; the β‐TCP reinforcement improved mechanical and hydrophilic behavior in comparison with PCL scaffolds. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43031.     

Preparation and characterization of Chitosan and PLGA‐based scaffolds for tissue engineering applications

Three dimensional (3D) biodegradable porous scaffolds play a crucial role in bone tissue repair. In this study, four types of 3D polymer/hydroxyapatite (HAp) composite scaffolds were prepared by freeze drying technique in order to mimic the organic/inorganic nature of the bone. Chitosan (CH) and poly(lactic acid‐co‐glycolic acid) (PLGA) were used as the polymeric part and HAp as the inorganic component. Properties of the resultant scaffolds, such as morphology, porosity, degradation, water uptake, mechanical and thermal stabilities were examined. 3D scaffolds having interconnected macroporous structure and 77–89% porosity were produced. The pore diameters were in the range of 6 and 200 µm. PLGA and HAp containing scaffolds had the highest compressive modulus. PLGA maintained the strength by decreasing water uptake but increased the degradation rate. Scaffolds seeded with SaOs‐2 osteoblast cells showed that all scaffolds were capable of encouraging cell adhesion and proliferation. The presence of HAp particles caused an increase in cell number on CH‐HAp scaffolds compared to CH scaffolds, while cell number decreased when PLGA was incorporated in the structure. CH‐PLGA scaffolds showed highest cell number on days 7 and 14 compared to others. Based on the properties such as interconnected porosity, high mechanical strength, and in vitro cell proliferation, blend scaffolds have the potential to be applied in hard tissue treatments. POLYM. COMPOS., 36:1917–1930, 2015. © 2014 Society of Plastics Engineers     

Preparation of chitosan-sodium alginate/bioactive glass composite cartilage scaffolds with high cell activity and bioactivity

Chitosan-sodium alginate/bioactive glass (CSB) composite cartilage scaffold with outstanding in vitro mineralization property and cytocompatibility is synthesized by freeze drying method. The effect of bioactive glass (BG) addition on the microstructure, porosity, swelling/degradation ratio, in vitro mineralization property and cytocompatibility of CSB scaffold is investigated by the characterization techniques of SEM, XRD, FTIR and BET. Results showed that CSB composite cartilage scaffold had a three-dimensional (3D) porous structure, and both porosity and average pore size met the requirements of cartilage tissue repair. Among, the typical CSB-1.0 had the largest overall pore size and lowest compressive modulus (1.083 ± 0.002 MPa). As the amount of BG increased, pore volume and porosity of CSB scaffolds gradually decreased, and the swelling and degradation ratios gradually reduced. After immersing in SBF for 3 d, cauliflower like hydroxyapatite (HA) was formed on CSB surface, indicating that the scaffold had good in vitro mineralization property. Moreover, the introduction of BG into the composite scaffold can improve the relative cell viability of MC3T3-E1 cells, and CSB-1.0 has the strongest ability to promote the proliferation of cells. Therefore, the as-obtained CSB scaffold can be used as a strong candidate for cartilage tissue engineering scaffold to meet clinical needs.     

Novel fabrication of hierarchically porous hydroxyapatite scaffolds with refined porosity and suitable strength

Based on extrusion deposition and foaming technique, a novel method for biological hydroxyapatite (HA) scaffolds was introduced in this paper. The scaffolds were primarily characterised by interconnected and hierarchically porous structures with high porosity, adjustable distribution of pore sizes, as well as considerable mechanical strength. In order to confirm that fine control of bulk porosity and mechanical strength was possible and feasible, further analysis of obtained scaffolds was carried out by field emission scanning electron microscope (FESEM), compressive test and calculation of volumetric shrinkage; in particular, the additional porosity resulting from the introduction of pore former was evaluated. The results indicated that this method can have a great potential to construct HA scaffolds of suitable quality for spongy bone in bone tissue engineering.     

Biofabrication of Gelatin Tissue Scaffolds with Uniform Pore Size via Microbubble Assembly

The control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications.     

Fabrication of a poly(ɛ‐caprolactone)/starch nanocomposite scaffold with a solvent‐casting/salt‐leaching technique for bone tissue engineering applications

A series of nanocomposite scaffolds of poly(?‐caprolactone) (PCL) and starch with a range of porosity from 50 to 90% were fabricated with a solvent‐casting/salt‐leaching technique, and their physical and mechanical properties were investigated. X‐ray diffraction patterns and Fourier transform infrared spectra confirmed the presence of the characteristic peaks of PCL in the fabricated scaffolds. Microstructure studies of the scaffolds revealed a uniform pore morphology and structure in all of the samples. The experimental measurements showed that the average contact angle of the PCL/starch composite was 88.05 ± 1.77°. All of the samples exhibited compressive stress/strain curves similar to those of polymeric foams. The samples with 50, 60, 70, and 80 wt % salt showed compressive‐load‐resisting capabilities in the range of human cancellous bone. With increasing porosity, a significant decrease in the mechanical properties of the scaffolds was observed. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43523.     

Solvent-Free Fabrication of Tissue Engineering Scaffolds With Immiscible Polymer Blends

A completely organic solvent-free fabrication method is developed for tissue engineering scaffolds by gas foaming of immiscible polylactic acid (PLA) and sucrose blends, followed by water leaching. PLA scaffolds with above 90% porosity and 25–200 µm pore size were fabricated. The pore size and porosity was controlled with process parameters including extrusion temperature and foaming process parameters. Dynamic mechanical analysis showed that the extrusion temperature could be used to control the scaffold strength. Both unfoamed and foamed scaffolds were used to culture glioblastoma (GBM) cells M059 K. The results showed that the cells grew better in the foamed PLA scaffolds. The method presented in the paper is versatile and can be used to fabricate tissue engineering scaffolds without any residual organic solvents.     

3D printing of porous scaffolds BaTiO3 piezoelectric ceramics and regulation of their mechanical and electrical properties

A series of porous scaffolds of piezoelectric ceramic barium titanate (BaTiO₃) were successfully fabricated by Digital Light Processing (DLP) 3D printing technology in this work. To obtain a high-precision and high-purity sample, the debinding sintering profile was explored and the optimal parameters were determined as 1425 °C for 2h. With the increase of scaffolds porosity from 10% to 90%, the compressive strength and piezoelectric coefficient (d₃₃) decreased gradually. The empirical formulas about the mechanical and piezoelectric properties were obtained by adjusting BaTiO₃ ceramics with different porosity. In addition, the distribution of potential and stress under 100 MPa pressure were studied by the finite element method (FEM).     

The Tunable Porous Structure of Gelatin–Bioglass Nanocomposite Scaffolds for Bone Tissue Engineering Applications: Physicochemical,Mechanical, and In Vitro Properties

Unidirectional freeze‐casting method is used to fabricate gelatin–bioglass nanoparticles (BGNPs) scaffolds. Transmission electron microscopy (TEM) images show that sol–gel prepared BGNPs are distributed throughout the scaffold with diameters of less than 10 nm. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetric are used to evaluate the physicochemical properties of BGNPs. Scanning electron microscopy (SEM) micrographs present an oriented porous structure and a homogeneous distribution of BGNPs in the gelatin matrix. The lamellar‐type structure indicates an improvement of mechanical strength and absorption capacity of the scaffolds. Increasing the concentration of BGNPs from 0 to 50 wt% have no noticeable effect on pore orientation, but decreases porosity and pore size distribution. Increase in BGNPs content improves the compressive strength. The absorption and biodegradation rate reduces with augmentation in BGNPs concentration. Bioactivity is evaluated through apatite formation after immersion of the nanocomposites in simulated body fluid and is verified by SEM–energy‐dispersive X‐ray spectroscopy (EDS), an element map analysis, X‐ray powder diffractometer, and FTIR spectrum. SEM images and methyl thiazolyl tetrazolium assay confirm the biocompatibility of scaffolds and the supportive behavior of nanocomposites in cellular spreading. The results show that gelatin–(30 wt%)bioglass nanocomposites have incipient physicochemical and biological properties.     

Three-dimensional printing of triply periodic minimal surface structured scaffolds for load-bearing bone defects

The porous and cellular architecture of scaffolds plays a significant role in mechanical strength and bone regeneration during the healing of fractured bones. In this present study, triply periodic minimal surface (TPMS)-based gyroid and primitive lattice structures were used to design the cellular porous biomimetic scaffolds with different unit cell sizes (4, 5, and 6). The fused filament fabrication-based 3D printing technology was used for the fabrication of polylactic acid scaffolds. The surface morphology and mechanical compressive strength of differently structured scaffolds were observed using scanning electron microscopy and a universal testing machine. The unit cell size of 4 showed higher compressive strength in both gyroid and primitive structured scaffolds compared to unit cell sizes 5 and 6. Moreover, the gyroid structured scaffolds have higher compressive strengths as compared to primitive structured scaffolds due to the higher bonding surface area at the intercalated layers of the scaffold. Hence, the mechanical strength of scaffolds can be tailored by varying the unit cell size and cellular structures to avoid stress shielding and ensure implant safety. These TPMS-based scaffolds are promising and can be used as bone substitute materials in tissue engineering and orthopedic applications.     

Bioactive and Biocompatible Macroporous Scaffolds with Tunable Performances Prepared Based on 3D Printing of the Pre‐Crosslinked Sodium Alginate/Hydroxyapatite Hydrogel Ink

Bioactive and biocompatible porous scaffold materials with adjustable pore structures and drug delivery capability are one of the key elements in bone tissue engineering. In this work, bioactive and biocompatible sodium alginate (SA)/hydroxyapatite (HAP) macroporous scaffolds are facilely and effectively fabricated based on 3D printing of the pre‐crosslinked SA/HAP hydrogels followed by further crosslinking to improve the mechanical properties of scaffolds. The pore structures and porosity (>80%) of the porous scaffolds can be readily tailored by varying the formation conditions. Furthermore, the in vitro biomineralization tests show that the bioactivity of the porous scaffolds is effectively enhanced by the addition of HAP nanoparticles into the scaffold matrix. Furthermore, the anti‐inflammatory drug curcumin is loaded into the porous scaffolds and the in vitro release study shows the sustainable drug release function of the porous scaffolds. Moreover, mouse bone mesenchymal stem cells (mBMSCs) are cultured on the porous scaffolds, and the results of the in vitro biocompatibility experiment show that the mBMSCs can be adhered well on the porous scaffolds. All of the results suggest that the bioactive and biocompatible SA/HAP porous scaffolds have great application potential in bone tissue engineering.