Scaffolds For Tissue Engineering Applications Research Articles

Durotaxis and Topotaxis Orchestrated Guidance on Cell Migration in 3D Printed Scaffold/Hydrogel Composite

Printing three-dimensional (3D) scaffolds with suitable mechanical cues is an effective strategy for guiding tissue regeneration by inducing cell migration and growth. Nevertheless, many studies considered only one type of cue for 3D tissue engineering scaffold fabrication, such as topological cues, which is insufficient. To realize durotaxis- and topotaxis-orchestrated guidance on cell migration, a 3D printed scaffold/hydrogel composite was fabricated in this study. The porous scaffold provided a topological cue (topotaxis), and the combined hydrogel provided a compliance cue (durotaxis). The results indicated that the thin fibers of the scaffold induced cell migration, and the larger pore size and directed fiber number of the scaffold led to more uniform cell orientation (topotaxis). Furthermore, when collagen was cured to cover the scaffold to result in a compliance change, the cells in the collagen still sensed the scaffold topological cue and migrated along it (durotaxis). Collagen also provides a living space and nutrition for cells, thereby significantly increasing their number. The effects of durotaxis and topotaxis synthesis provide a promising solution for tissue engineering scaffold applications.

A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

AbstractMelt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering applications. However, most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate. Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct; however, there are limited strategies available to control the surface density. Here, we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k (PCL5k) containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios. Stable porous three-dimensional (3D) scaffolds were then fabricated using a high weight percentage (75 wt.%) of the low molecular weight PCL5k. As a proof-of-concept test, we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface, yielding a density of 201–561 pmol/cm2. Subsequently, a bone morphogenetic protein 2 (BMP-2)-derived peptide was grafted onto the films comprising different blend compositions, and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was assessed. After two weeks of culturing in a basic medium, cells expressed higher levels of BMP receptor II (BMPRII) on films with the conjugated peptide. In addition, we found that alkaline phosphatase activity was only significantly enhanced on films containing the highest peptide density (i.e., 561 pmol/cm2), indicating the importance of the surface density. Taken together, these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface. Moreover, we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of (modified) polymers. Furthermore, the use of alkyne–azide “click” chemistry enables spatial control over bioconjugation of many tissue-specific moieties, making this approach a versatile strategy for tissue engineering applications. Graphic abstract

3D-printed scaffolds for tissue engineering applications using thermosensitive hydrogels based on biopolymer blends

AbstractThree-dimensional (3D) printing is an emerging technology for the construction of complex 3D constructs used for tissue engineering applications. In this study, we are proposing the preparation of 3D printing hydrogel inks consisting of the synthetic polymers poly(caprolactone) and poly(lactic acid), the biopolymer chitosan, and naturally derived gelatin. In addition, pluronic F-127 was used to improve the miscibility between the hydrophobic and hydrophilic components due to its amphiphilic character, as well as for its good 3D printability. The printability of the hydrogel inks was optimized by varying the composition, the extrusion nozzle, and the temperature, while the integrity of the 3D scaffolds was secured via sol–gel transition. The produced hydrogels with PCL-pluronic-chitosan-gelatin/15-20-4-2 wt% (PC3.75-Pl5-CG) and PLA-pluronic-chitosan-gelatin/10-20-4-2 wt% (PL2.5-Pl5-CG) presented the best printability, producing smooth and uniform porous scaffolds. The prepared hydrogels were formed via the interactions between the polymers through hydrogen bonding. Additionally, the produced hydrogels exhibited temperature-dependent swelling behavior, and the scaffolds with PCL presented lower swelling capacity than the scaffolds with PLA. The produced scaffolds presented slower hydrolyzation rate in simulated body fluid (SBF) at 25 °C compared to 37 °C. Biological studies proved that the 3D-printed porous scaffolds were non-cytotoxic and promoted human adipose-derived mesenchymal stem cell adhesion. Graphical abstract

Investigating long term storage stability and drug release behavior of polypeptide based fibrous scaffold for tissue engineering application

Electrospun poly (γ-benzyl-L-glutamate) (PBG) scaffold felt with aligned fibers shows promising nerve regeneration and neurite growth capability due to the nerve stimulating moiety of glutamate in the PBG material. The nerve regeneration capability can be further enhanced by incorporating 4wt% minocycline hydrochloride (MH) in the scaffold (PBGMH4). They are useful in the nerve tissue engineering to repair and regeneration damaged nerves in central nerve system or peripheral nerve system. Here we investigate the ambient storage capability of PBG and PBGMH4 by monitoring the changes over time of fiber dimension, mechanical properties of both scaffolds and amount of drug release of PBGMH4. It is interesting to observe the diameter of fibers and mechanical strength of scaffolds increases but the amount of drug release decrease with time. By carefully examining the top view of the scaffolds using scanning electron microscopy (SEM), the fiber diameter of PBG increased by 58% over the 12 months storage period, which is larger than the 32% increase observed for PBGMH4. Furthermore, after storage for 12 months, the difference in fiber diameter between the top and bottom sides of PBG scaffold is 25.9%, whereas for PBGMH4 is only 6.3%. These results demonstrate that the PBGMH4 scaffold exhibits superior storage stability compared to that of PBG. Because the fibers of the scaffolds are aligned without any crosslinkage, the scaffolds are porous structure of felts. The porosity of PBGMH4 scaffold is decreased from 90% to 72% which can be accountable for the decrease of drug release from initial 42% to a stabilized 26% after 9 months of storage. The results indicate the specific surface area of the scaffolds play an important role in governing drug release kinetics. This study thoroughly investigates the storage stability of PBG and PBGMH4 electrospun fibrous scaffolds. The observed correlations between fiber diameter, mechanical properties, and drug release behavior hold implications for the design of advanced bioscaffolds. The long shelf life of optimal PBGMH4 scaffold shows potential application for the nerve regeneration and controlled drug delivery systems.

Fabrication of poly(xylitol‐citrate‐sebacate) and strontium‐doped mesoporous bioactive glass scaffold for tissue engineering application

AbstractIn this study, strontium‐doped mesoporous bioactive glass nanoparticles (Sr‐MBGNs) were incorporated into a poly(xylitol‐citrate‐sebacate) (PXCS) matrix using solution mixing techniques. The resulting composites, including PXCS, PXCS/1.5% Sr‐MBGNs, PXCS/3% Sr‐MBGNs, and PXCS/5% Sr‐MBGNs, were characterized for biomedical applications using FTIR, DSC, and x‐ray diffraction analyses. High‐resolution scanning electron microscopy (HRSEM) and a universal testing machine were employed to investigate the structure, morphology, and mechanical properties of the polymer and its nanocomposites. Our findings indicate that the introduction of polymer and its nanocomposites minimally affects the glass transition and crystallinity. The observed decrease in glass transition temperature with increasing Sr‐MBGNs content suggests a plasticizing effect. These results are consistent with previous studies. Additionally, in vitro studies were conducted to evaluate antibacterial properties, VERO cell line proliferation, degradation, and swelling percentage of the scaffolds. Metal ions release behavior was assessed using inductively coupled plasma atomic emission spectrometry (ICP‐AES) Furthermore, the drug loading and release of curcumin from PXCS/5% Sr‐MBGNs and PXCS/Sr‐MBGNs nanocomposite scaffolds were investigated at varying pH levels (pH: 5.5, 6.8, and 7.4). Both PXCS/5% Sr‐MBGNs and PXCS/5% Sr‐MBGNs scaffolds demonstrated enhanced biological properties, highlighting their potential for use in bone regeneration approaches.

On fused filament fabrication of PLA nanofiber reinforced PCL matrix-based smart porous scaffolds

In the past, studies were reported on polycaprolactone (PCL) and polylactic acid (PLA) nanofibers (NF)-based scaffolds for tissue engineering applications. But hitherto, little has been reported on the sensing capability of PLA-NF reinforced PCL composite (PPNC)-based smart porous scaffolds for online health monitoring (OHM) of joint strains/ tendon tears/ contusions/ rhabdomyolysis, etc. In this study, smart porous scaffolds (SPS) were fabricated by fused filament fabrication (FFF) using PPNC for OHM (of joint strains/ tendon tears/ contusions/ rhabdomyolysis, etc.) with tuneable sensing and mechanical properties. The results suggest that FFF parameters, zigzag fill pattern, 0.20 mm layer thickness, and 80 % infill percentage are the best-predicted settings for maximum yield stress (σymax) of SPS. Further, a vector network analyzer was used to ascertain the sensing capability of SPS. The resonance frequency (Rf) for PCL (virgin) and PPNC with minimum yield stress (σymin) and σymax were observed as 2.3021, 2.6008, and 2.4315 GHz respectively. The simulated return loss (S11), specific absorption ratio (SAR), and Rf for PCL (−10.7593 dB, 0.977 W/kg, and 2.6450 GHz), PPNC with σymin (−10.5737 dB, 1.437 W/kg and 2.3400 GHz) and PPNC with σymax (−10.9429 dB, 1.155 W/kg and 2.5050 GHz) indicate that experimental data is in good co-relation with the observed values. The results are supported by a scanning electron microscope and differential scanning calorimetry.

Confined Water Dynamics in the Scaffolds of Polylactic Acid.

Resorbable polylactic acid (PLA) ultrathin fibers have been applied as scaffolds for tissue engineering applications due to their micro- and nanoporous structure that favor cell adhesion, besides inducing cell proliferation and upregulating gene expression related to tissue regeneration. Incorporation of multiwalled carbon nanotubes into PLA fibers has been reported to increase the mechanical properties of the scaffold, making them even more suitable for tissue engineering applications. Ideally, scaffolds should be degraded simultaneously with tissue growth. Hydration and swelling are factors related to scaffold degradation. Hydration would negatively impact the mechanical properties since PLA shows hydrolytic degradation. Water absorption critically affects the catalysis and allowance of the hydrolysis reactions. Moreover, either mass transport and chemical reactions are influenced by confined water, which is an unexplored subject for PLA micro- and nanoporous fibers. Here, we probe and investigate confined water onto highly porous PLA microfibers containing few amounts of incorporated carbon nanotubes by Fourier transform infrared (FTIR) spectroscopy. A hydrostatic pressure was applied to the fibers to enhance the intermolecular interactions between water molecules and C=O groups from polyester bonds, which were evaluated over the wavenumber between 1600 and 2000 cm-1. The analysis of temperature dependence of FTIR spectra indicated the presence of confined water which is characterized by a non-Arrhenius to Arrhenius crossover at T0 = 190 K for 1716 and 1817 cm-1 carbonyl bands of PLA. These bands are sensitive to a hydrogen bond network of confined water. The relevance of our finding relies on the challenge detecting confined water in hydrophobic cavities as in the PLA one. To the best of our knowledge, we present the first report referring the presence of confined water in a hydrophobic scaffold as PLA for tissue engineering. Our findings can provide new opportunities to understand the role of confined water in tissue engineering applications. For instance, we argue that PLA degradation may be affected the most by confined water. PLA degradation involves hydrolytic and enzymatic degradation reactions, which can both be sensitive to changes in water properties.

Carbon nanomaterials‐based electrically conductive scaffolds for tissue engineering applications

Carbon nanomaterials‐based electrically conductive scaffolds for tissue engineering applications

Effect of graphite, graphene oxide, and multi-walled carbon nanotubes on the physicochemical characteristics and biocompatibility of chitosan/hyaluronic acid/hydroxyapatite scaffolds for tissue engineering applications

Bone tissue engineering (BTE) is a promising alternative approach to the repair of damaged bone tissue. This study aims to fabricate and characterize scaffolds composed of chitosan (CS), hyaluronic acid (HA), hydroxyapatite (HAp), and a combination of graphite (Gr), graphene oxide (GO), and multi-walled carbon nanotubes (MWCNT) for BTE applications. The Gr and MWCNT were functionalized by acid oxidation, while the GO was synthesized using the improved Hummers' method. The scaffolds were prepared by lyophilization, and the physical, chemical, and biological properties were evaluated. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, mechanical testing, water contact angle, degradation, and biocompatibility assays were used to characterize the scaffolds. The degradation rate was determined using the liquid displacement method. Pores of different sizes were present on the surface of and throughout the scaffold. According to the FTIR results, the scaffolds contained functional groups that promote cell differentiation and proliferation. These scaffolds have compressive strength, Young's modulus, and toughness similar to cancellous bone, with reasonable porosity and controllable degradation rates. Biocompatibility testing confirmed that the scaffolds support cell proliferation and differentiation.

Biodegradable microfibrous, electrospunned hydroxyapatite nanoparticles/poly(glycerol sebacate)-co-poly(ε-caprolactone) nanocomposite scaffolds for tissue engineering applications

Biodegradable microfibrous, electrospunned hydroxyapatite nanoparticles/poly(glycerol sebacate)-co-poly(ε-caprolactone) nanocomposite scaffolds for tissue engineering applications

Sustainable highly stretchable and tough gelatin-alkali lignin hydrogels for scaffolding and 3D printing applications

Hydrogels and bioinks obtained from gelatin (Gel) generally present poor mechanical properties and require a series of time-consuming and stepwise chemical processes to exhibit improved elasticity and resistance to fatigue. Alkali lignin (AL) is an underutilized by-product of the paper and pulp industry. It is a widely available and inexpensive biomaterial that presents enormous potential for high-value applications owing to its ease of chemical modification and unique naturally occurring polyaromatic structure. This work aims to develop different GelAL hydrogel formulations with a single-step method that are innovative and sustainable. The results obtained from the mechanical, rheological, and degradation studies of the developed GelAL hydrogels demonstrated that their properties can be easily modified and tuned using straightforward processing techniques, allowing these stretchable and tough hydrogels to be used as bioinks in 3D printing. The modulation of mechanical properties through hydrogel formulations is a result of interactions between the Gel and AL which can be associated with the interplay of anionic sulfonates in AL and the arginine and lysine residues from Gel. The tensile stress at the break for the Gel20AL10 formulation was 32% higher than the value for Gel20AL5 and 157% higher than that of Gel10AL10. The elongation at break also decreased as it averaged 659 ± 149% for the Gel20AL10 formulation, which is 20% more than that of Gel20AL5 and 55% more than the average elongation at break of Gel10AL10. Further zeta potential measurements and quartz crystal microbalance with energy dissipation studies demonstrated that Gel and AL seem to form neutral complexes when mixed. These assays support the idea that AL and Gel are readily bound through weak interactions, and chemical crosslinking strategies need to be considered when degradability and mechanical properties tuning are envisioned. Altogether, these high-performance GelAL hydrogels display mechanical properties similar to soft tissues with high elasticity beyond that of natural hydrogels and fulfill the requirements of a broad range of biomedical and tissue engineering scaffolding applications.

Mechanical properties of native and decellularized reproductive tissues: insights for tissue engineering strategies

Understanding the mechanical properties and porosity of reproductive tissues is vital for regenerative medicine and tissue engineering. This study investigated the changes in Young's modulus (YM), storage modulus (E′), loss modulus (Eʺ), and porosity of native and decellularized bovine reproductive tissues during the estrous cycle. Testis tunica albuginea had significantly higher YM, E′, and Eʺ than the inner testis, indicating greater stiffness and viscoelasticity. Endometrium showed no distinct differences in YM, E′, or Eʺ across the estrous cycle or between horns. Ovaries exhibited significant variations in YM, E′, Eʺ, and porosity, with higher YM and E′ in the ipsilateral cortex and medulla during the luteal phase. Decellularized ovarian tissues displayed increased porosity. The oviduct displayed no significant differences in YM or E′ in the isthmus, but the contralateral ampulla had reduced YM and E′ in the luteal phase. These findings offer valuable insights into the dynamic mechanical properties and porosity of reproductive tissues, facilitating the development of biomimetic scaffolds for tissue engineering applications.

Tailoring mechanical properties of printed GelMA scaffolds with multilayers of PLA/Laponite nanocomposite fibers

This study focuses on the fabrication and evaluation of hybrid scaffolds of printed GelMA hydrogels reinforced with multilayered Poly(Lactic Acid) (PLA)/Laponite (LAP) microfibrous membranes. PLA microfibers with different amounts of LAP (0, 1.0, 2.5, and 5%) were prepared by rotary-jet spinning and subjected to oxygen plasma treatment. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and x-ray diffraction (XRD) were used for morphological and compositional analyzes. Their mechanical properties were evaluated by uniaxial tensile tests, showing the improved mechanical strength by the incorporation of LAP, specially in the PLA/ LAP 2.5% group. Then, the microfibrous membranes were integrated into printed GelMA hydrogel layers, resulting in GelMA-PLA/LAP hybrid scaffolds, whose interaction and integrity were confirmed by SEM. The mechanical evaluation using uniaxial compression tests showed a significant improvement in the mechanical properties of the hybrid scaffolds which can be attributed to the inclusion of microfibrous membranes. These results highlight the potential benefits of GelMA-PLA/LAP scaffolds for tissue engineering applications by leveraging the mechanical reinforcement provided by the PLA/LAP microfibrous layers.

Biodegradable and 3D printable lysine functionalized polycaprolactone scaffolds for tissue engineering applications

Tissue engineering (TE) has sparked interest in creating scaffolds with customizable properties and functional bioactive sites. However, due to limitations in medical practices and manufacturing technologies, it is challenging to replicate complex porous frameworks with appropriate architectures and bioactivity in vitro. To address these challenges, herein, we present a green approach that involves the amino acid (l-lysine) initiated polymerization of ɛ-caprolactone (CL) to produce modified polycaprolactone (PCL) with favorable active sites for TE applications. Further, to better understand the effect of morphology and porosity on cell attachment and proliferation, scaffolds of different geometries with uniform and interconnected pores are designed and fabricated, and their properties are evaluated in comparison with commercial PCL. The scaffold morphology and complex internal micro-architecture are imaged by micro-computed tomography (micro-CT), revealing pore size in the range of ~300–900 μm and porosity ranging from 30 to 70 %, while based on the geometry of scaffolds the compressive strength varied from 143 ± 19 to 214 ± 10 MPa. Additionally, the degradation profiles of fabricated scaffolds are found to be influenced by both the chemical nature and product design, where Lys-PCL-based scaffolds with better porosity and lower crystallinity degraded faster than commercial PCL scaffolds. According to in vitro studies, Lys-PCL scaffolds have produced an environment that is better for cell adhesion and proliferation. Moreover, the scaffold design affects the way cells interact; Lys-PCL with zigzag geometry has demonstrated superior in vitro vitality (>90 %) and proliferation in comparison to other designs. This study emphasizes the importance of enhancing bioactivity while meeting morphology and porosity requirements in the design of scaffolds for tissue engineering applications.

Chitosan Poly(vinyl alcohol) Methacrylate Hydrogels for Tissue Engineering Scaffolds.

A major challenge in tissue engineering scaffolds is controlling scaffold degradation rates during healing while maintaining mechanical properties to support tissue formation. Hydrogels are three-dimensional matrices that are widely applied as tissue scaffolds based on their unique properties that can mimic the extracellular matrix. In this study, we develop a hybrid natural/synthetic hydrogel platform to tune the properties for tissue engineering scaffold applications. We modified chitosan and poly(vinyl alcohol) (PVA) with photo-cross-linkable methacrylate functional groups and then synthesized a library of chitosan PVA methacrylate hydrogels (ChiPVAMA) with two different photoinitiators, Irgacure 2959 (I2959) and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). ChiPVAMA hydrogels showed tunability in degradation rates and mechanical properties based on both the polymer content and photoinitiator type. This tunability could enable their application in a range of tissue scaffold applications. In a 2D scratch wound healing assay, all hydrogel samples induced faster wound closure compared to a gauze clinical wound dressing control. NIH/3T3 cells encapsulated in hydrogels showed a high viability (∼92%) over 14 days, demonstrating the capacity of this system as a supportive cell scaffold. In addition, hydrogels containing a higher chitosan content demonstrated a high antibacterial capacity. Overall, ChiPVAMA hydrogels provide a potential tissue engineering scaffold that is tunable, degradable, and suitable for cell growth.

Hydrogel Based on Chitosan/Gelatin/Poly(Vinyl Alcohol) for In Vitro Human Auricular Chondrocyte Culture.

Three-dimensional (3D) hydrogels provide tissue-like complexities and allow for the spatial orientation of cells, leading to more realistic cellular responses in pathophysiological environments. There is a growing interest in developing multifunctional hydrogels using ternary mixtures for biomedical applications. This study examined the biocompatibility and suitability of human auricular chondrocytes from microtia cultured onto steam-sterilized 3D Chitosan/Gelatin/Poly(Vinyl Alcohol) (CS/Gel/PVA) hydrogels as scaffolds for tissue engineering applications. Hydrogels were prepared in a polymer ratio (1:1:1) through freezing/thawing and freeze-drying and were sterilized by autoclaving. The macrostructure of the resulting hydrogels was investigated by scanning electron microscopy (SEM), showing a heterogeneous macroporous structure with a pore size between 50 and 500 μm. Fourier-transform infrared (FTIR) spectra showed that the three polymers interacted through hydrogen bonding between the amino and hydroxyl moieties. The profile of amino acids present in the gelatin and the hydrogel was determined by ultra-performance liquid chromatography (UPLC), suggesting that the majority of amino acids interacted during the formation of the hydrogel. The cytocompatibility, viability, cell growth and formation of extracellular matrix (ECM) proteins were evaluated to demonstrate the suitability and functionality of the 3D hydrogels for the culture of auricular chondrocytes. The cytocompatibility of the 3D hydrogels was confirmed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reaching 100% viability after 72 h. Chondrocyte viability showed a high affinity of chondrocytes for the hydrogel after 14 days, using the Live/Dead assay. The chondrocyte attachment onto the 3D hydrogels and the formation of an ECM were observed using SEM. Immunofluorescence confirmed the expression of elastin, aggrecan and type II collagen, three of the main components found in an elastic cartilage extracellular matrix. These results demonstrate the suitability and functionality of a CS/Gel/PVA hydrogel as a 3D support for the auricular chondrocytes culture, suggesting that these hydrogels are a potential biomaterial for cartilage tissue engineering applications, aimed at the regeneration of elastic cartilage.

Development and Evaluation of Biodegradable Core-Shell Microfibrous and Nanofibrous Scaffolds for Tissue Engineering Applications

Tissue engineering scaffolds as three-dimensional substrates may serve as ideal templates for tissue regeneration by simulating the structure of the extracellular matrix (ECM). Many biodegradable synthetic polymers, either hydrophobic, like Poly-ε-caprolactone (PCL), or hydrophilic, like Poly(Vinyl Alcohol) (PVA), are widely used as candidate bioactive materials for fabricating tissue engineering scaffolds. However, a combination of good cytocompatibility of hydrophilic polymers with good biomechanical performance of hydrophobic polymers could be beneficial for the in vivo performance of the scaffolds. In this study, we aimed to fabricate biodegradable fibrous scaffolds by combining the properties of hydrophobic PCL with those of hydrophilic PVA and evaluate their properties in comparison with pristine PCL scaffolds. Therefore, single-layered PCL scaffolds, sequential tri-layered (PVA/PCL/PVA), and core-shell (PVA as shell and PCL as core) composite scaffolds were developed utilizing the electrospinning technique. The material structural and biomechanical properties of the electrospun scaffolds, before and after their hydrolytic degradation over a seven-month period following storage in phosphate-buffered saline (PBS) at 37 °C, were comprehensively compared. In addition, human embryonic kidney cells (HEK-293) were cultured on the scaffolds to investigate potential cell attachment, infiltration, and proliferation. The results demonstrated the long-term efficacy of core-shell biodegradable fibrous scaffolds in comparison to single-layers PCL and tri-layers PVA/PCL/PVA, not only due to its superior morphological characteristics and mechanical properties, but also due to its ability to promote homogeneous cell distribution and proliferation, without any external chemical or physical stimuli.Graphical

A Combined Computational and Experimental Analysis of PLA and PCL Hybrid Nanocomposites 3D Printed Scaffolds for Bone Regeneration.

A combined computational and experimental study of 3D-printed scaffolds made from hybrid nanocomposite materials for potential applications in bone tissue engineering is presented. Polycaprolactone (PCL) and polylactic acid (PLA), enhanced with chitosan (CS) and multiwalled carbon nanotubes (MWCNTs), were investigated in respect of their mechanical characteristics and responses in fluidic environments. A novel scaffold geometry was designed, considering the requirements of cellular proliferation and mechanical properties. Specimens with the same dimensions and porosity of 45% were studied to fully describe and understand the yielding behavior. Mechanical testing indicated higher apparent moduli in the PLA-based scaffolds, while compressive strength decreased with CS/MWCNTs reinforcement due to nanoscale challenges in 3D printing. Mechanical modeling revealed lower stresses in the PLA scaffolds, attributed to the molecular mass of the filler. Despite modeling challenges, adjustments improved simulation accuracy, aligning well with experimental values. Material and reinforcement choices significantly influenced responses to mechanical loads, emphasizing optimal structural robustness. Computational fluid dynamics emphasized the significance of scaffold permeability and wall shear stress in influencing bone tissue growth. For an inlet velocity of 0.1 mm/s, the permeability value was estimated at 4.41 × 10-9 m2, which is in the acceptable range close to human natural bone permeability. The average wall shear stress (WSS) value that indicates the mechanical stimuli produced by cells was calculated to be 2.48 mPa, which is within the range of the reported literature values for promoting a higher proliferation rate and improving osteogenic differentiation. Overall, a holistic approach was utilized to achieve a delicate balance between structural robustness and optimal fluidic conditions, in order to enhance the overall performance of scaffolds in tissue engineering applications.

Effects of mechanical properties of carbon-based nanocomposites on scaffolds for tissue engineering applications: a comprehensive review.

Mechanical properties, such as elasticity modulus, tensile strength, elongation, hardness, density, creep, toughness, brittleness, durability, stiffness, creep rupture, corrosion and wear, a low coefficient of thermal expansion, and fatigue limit, are some of the most important features of a biomaterial in tissue engineering applications. Furthermore, the scaffolds used in tissue engineering must exhibit mechanical and biological behaviour close to the target tissue. Thus, a variety of materials has been studied for enhancing the mechanical performance of composites. Carbon-based nanostructures, such as graphene oxide (GO), reduced graphene oxide (rGO), carbon nanotubes (CNTs), fibrous carbon nanostructures, and nanodiamonds (NDs), have shown great potential for this purpose. This is owing to their biocompatibility, high chemical and physical stability, ease of functionalization, and numerous surface functional groups with the capability to form covalent bonds and electrostatic interactions with other components in the composite, thus significantly enhancing their mechanical properties. Considering the outstanding capabilities of carbon nanostructures in enhancing the mechanical properties of biocomposites and increasing their applicability in tissue engineering and the lack of comprehensive studies on their biosafety and role in increasing the mechanical behaviour of scaffolds, a comprehensive review on carbon nanostructures is provided in this study.

TISSUE SCAFFOLDING: AN UPCOMING TISSUE FABRICATION TECHNIQUE

Tissue engineering (TE) is a multidisciplinary research that combines clinical medicine, biology, biochemistry, and materials science. TE involves the creation of scaffolds that can replicate the characteristics of the extracellular matrix (ECM) of tissues to ensure complete and whole regeneration. During the past decade, a wide range of materials have been chosen for bone tissue engineering and combined with these production techniques. Several production methods, including electro-spinning, freeze-drying, bio-printing, and de-cellularization, have been used to create scaffolds for tissue engineering applications. In this paper, we review the capabilities and operating methods of the most promising techniques for the future.