Mechanical Properties Of Scaffolds Research Articles

Psidium guajava L. phenolic compound-reinforced lamellar scaffold for tracheal tissue engineering

The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resistance for the 0.3% TFC formulation. The addition of TPC percentages did not result in a significant difference (p > 0.05) in swelling capacity and disintegration rate. The results confirmed that TPC were able to modulate the morphological, morphometric, and mechanical properties of scaffolds. Thus, this study describes a potential new material to improve the regeneration of major tracheal structures after surgical tumor removal.Graphical

Mechanical influence of tissue scaffolding design with different geometries using finite element study.

The mechanical properties of tissue scaffolds are essential in providing stability for tissue repair and growth. Thus, the ability of scaffolds to withstand specific loads is crucial for scaffold design. Most research on scaffold pores focuses on grids with pore size and gradient structure, and many research models are based on scaffolding with vertically arranged holes. However, little attention is paid to the influence of the distribution of holes on the mechanical properties of the scaffold. To address this gap, this research investigates the effect of pore distribution on the mechanical properties of tissue scaffolds. The study involves four types of scaffold designs with regular and staggered pore arrangements and porosity ranging from 30% to 80%. Finite element analysis (FEA) was used to compare the mechanical properties of different scaffold designs, with von-Mises stress distribution maps generated for each scaffold. The results show that scaffolds with regular vertical holes exhibit a more uniform stress distribution and better mechanical performance than those with irregular holes. In contrast, the scaffold with a staggered arrangement of holes had a higher probability of stress concentration. The study emphasized the importance of balancing porosity and strength in scaffold design.

Printing tissue-engineered scaffolds made of polycaprolactone and nano-hydroxyapatite with mechanical properties appropriate for trabecular bone substitutes

BackgroundBone tissue engineering, based on three-dimensional (3D) printing technology, has emerged as a promising approach to treat bone defects using scaffolds. The objective of this study was to investigate the influence of porosity and internal structure on the mechanical properties of scaffolds.MethodsWe fabricated composite scaffolds (which aimed to replicate trabecular bone) from polycaprolactone (PCL) reinforced with 30% (wt.) nano-hydroxyapatite (nHAp) by extrusion printing. Scaffolds with various porosities were designed and fabricated with and without an interlayer offset, termed as staggered and lattice structure, respectively. Mechanical compressive testing was performed to determine scaffold elastic modulus and yield strength. Linear regression was used to evaluate mechanical properties as a function of scaffold porosity.ResultsDifferent relationships between mechanical properties and porosities were noted for the staggered and lattice structures. For elastic moduli, the two relationships intersected (porosity = 55%) such that the lattice structure exhibited higher moduli with porosity values greater than the intersection point; vice versa for the staggered structure. The lattice structure exhibited higher yield strength at all porosities. Mechanical testing results also indicated elastic moduli and yield strength properties comparable to trabecular bone (elastic moduli: 14–165 MPa; yield strength: 0.9–10 MPa).ConclusionsTaken together, this study demonstrates that scaffolds printed from PCL/30% (wt.) nHAp with lattice and staggered structure offer promise for treating trabecular bone defects. This study identified the effect of porosity and internal structure on scaffold mechanical properties and provided suggestions for developing scaffolds with mechanical properties for substituting trabecular bone.

Can we achieve biomimetic electrospun scaffolds with gelatin alone?

Introduction: Gelatin is a natural polymer commonly used in biomedical applications in combination with other materials due to its high biocompatibility, biodegradability, and similarity to collagen, principal protein of the extracellular matrix (ECM). The aim of this study was to evaluate the suitability of gelatin as the sole material to manufacture tissue engineering scaffolds by electrospinning. Methods: Gelatin was electrospun in nine different concentrations onto a rotating collector and the resulting scaffold's mechanical properties, morphology and topography were assessed using mechanical testing, scanning electron microscopy and white light interferometry, respectively. After characterizing the scaffolds, the effects of the concentration of the solvents and crosslinking agent were statistically evaluated with multivariate analysis of variance and linear regressions. Results: Fiber diameter and inter-fiber separation increased significantly when the concentration of the solvents, acetic acid (HAc) and dimethyl sulfoxide (DMSO), increased. The roughness of the scaffolds decreased as the concentration of dimethyl sulfoxide increased. The mechanical properties were significantly affected by the DMSO concentration. Immersed crosslinked scaffolds did not degrade until day 28. The manufactured gelatin-based electrospun scaffolds presented comparable mechanical properties to many human tissues such as trabecular bone, gingiva, nasal periosteum, oesophagus and liver tissue. Discussion: This study revealed for the first time that biomimetic electrospun scaffolds with gelatin alone can be produced for a significant number of human tissues by appropriately setting up the levels of factors and their interactions. These findings also extend statistical relationships to a form that would be an excellent starting point for future research that could optimize factors and interactions using both traditional statistics and machine learning techniques to further develop specific human tissue.

3D Printing of Collagen Nerve Scaffold with Multichannel Characteristics

Given the difficulty in preparing multichannel nerve scaffolds for peripheral nerve repair, a method of manufacturing multichannel collagen nerve scaffolds by multi-nozzle 3D printing technology was proposed. Gelatin material is used as the core melting material because of its temperature-sensitive characteristics. A collagen nerve scaffold with a multichannel structure was manufactured by temperature-rising removal after printing, and the scaffold with different collagen concentrations was analyzed and evaluated in terms of microtubule diameter and mechanical properties. The research results show that the mechanical properties of the scaffold are gradually enhanced with an increase in collagen concentration. When the concentration of collagen is between 5% and 6%, the quality of the microtubule is significantly improved compared with the 4% collagen scaffold. Combined with the distribution of microtubule diameter, a lower concentration of collagen will lead to the collapse and deformation of the print structure, while a higher concentration of collagen will lead to the existence of voids in the print structure. Considering the manufacturing process, microtubule diameter, and mechanical properties of collagen nerve scaffold, 5% collagen nerve scaffold is the best and is expected to meet the requirements of peripheral nerve regeneration.

Three-Dimensional Scaffolds for Bone Tissue Engineering.

Immobilization using external or internal splints is a standard and effective procedure to treat minor skeletal fractures. In the case of major skeletal defects caused by extreme trauma, infectious diseases or tumors, the surgical implantation of a bone graft from external sources is required for a complete cure. Practical disadvantages, such as the risk of immune rejection and infection at the implant site, are high in xenografts and allografts. Currently, an autograft from the iliac crest of a patient is considered the "gold standard" method for treating large-scale skeletal defects. However, this method is not an ideal solution due to its limited availability and significant reports of morbidity in the harvest site (30%) as well as the implanted site (5-35%). Tissue-engineered bone grafts aim to create a mechanically strong, biologically viable and degradable bone graft by combining a three-dimensional porous scaffold with osteoblast or progenitor cells. The materials used for such tissue-engineered bone grafts can be broadly divided into ceramic materials (calcium phosphates) and biocompatible/bioactive synthetic polymers. This review summarizes the types of materials used to make scaffolds for cryo-preservable tissue-engineered bone grafts as well as the distinct methods adopted to create the scaffolds, including traditional scaffold fabrication methods (solvent-casting, gas-foaming, electrospinning, thermally induced phase separation) and more recent fabrication methods (fused deposition molding, stereolithography, selective laser sintering, Inkjet 3D printing, laser-assisted bioprinting and 3D bioprinting). This is followed by a short summation of the current osteochondrogenic models along with the required scaffold mechanical properties for in vivo applications. We then present a few results of the effects of freezing and thawing on the structural and mechanical integrity of PLLA scaffolds prepared by the thermally induced phase separation method and conclude this review article by summarizing the current regulatory requirements for tissue-engineered products.

A Unification of Nanotopography and Extracellular Matrix in Electrospun Scaffolds for Bioengineered Hepatic Models.

Donor liver shortage is a crucial global public health problem as whole-organ transplantation is the only definitive cure for liver disease. Liver tissue engineering aims to reproduce or restore function through in vitro tissue constructs, which may lead to alternative treatments for active and chronic liver disease. The formulation of a multifunctional scaffold that has the potential to mimic the complex extracellular matrix (ECM) and their influence on cellular behavior, are essential for culturing cells on a construct. The separate employment of topographic or biological cues on a scaffold has both shown influences on hepatocyte survival and growth. In this study, we investigate both of these synergistic effects and developed a new procedure to directly blend whole-organ vascular perfusion-decellularized rat liver ECM (dECM) into electrospun fibers with tailored surface nanotopography. Water contact angle, tensile test, and degradation studies were conducted to analyze scaffold hydrophilicity, mechanical properties, and stability. The results show that our novel hybrid scaffolds have enhanced hydrophilicity, and the nanotopography retained its original form after hydrolytic degradation for 14 days. Human hepatocytes (HepG2) were seeded to analyze the scaffold biocompatibility. Cell viability and DNA quantification imply steady cell proliferation over the culture period, with the highest albumin secretion observed on the hybrid scaffold. Scanning electron microscopy shows that cell morphology was distinctly different on hybrid scaffolds compared to control groups, where HepG2 began to form a monolayer toward the end of the culture period; meanwhile, typical hepatic markers and ECM genes were also influenced, such as an increasing trend of albumin appearing on the hybrid scaffolds. Taken together, our findings provide a reproducible approach and utilization of animal tissue-derived ECM and emphasize the synergism of topographical stimuli and biochemical cues on electrospun scaffolds in liver tissue engineering.

Fabrication of polycaprolactone/chitosan/hydroxyapatite structure to improve the mechanical behavior of the hydrogel‐based scaffolds for bone tissue engineering: Biscaffold approach

AbstractThe main idea of this study is to create a 3D printed scaffold to improve the mechanical behavior of hydrogels for bone tissue engineering. This paper investigated the effects of infill percentage and strand diameter on the 3D printed polycaprolactone/Chitosan/HA scaffold's mechanical properties. The printing parameters were optimized by central composite design in response surface methodology. The X, Y, and Z axes measured stiffness (N/m), compressive strength (MPa), and elongation at break (%). The results showed that the highest stiffness of all samples (in both vertical (65 MPa) and horizontal (32 MPa) loading dimensions) could be found in the scaffolds with 40% infill and the strands with 400 μm diameter. It was also indicated that the degradability of the samples could be improved (0.33%–1.03%) with a reduction of strand diameter from 600 to 400 μm. The most swelling was attributed to the scaffold with 50% infill and strand diameter of 600 μm. Hydrophilicity was improved by employing chitosan (78.3°–66.3°). Results depicted good biocompatibility (>80%) of the samples. To sum up, the idea of a biscaffold with suitable engineering can be a good idea to enhance the mechanical behavior of hydrogel‐based scaffolds.

Structure, Piezoresponse, and Physical and Mechanical Properties of Scaffolds Based on Polyhydroxybutyrate with a Magnetite/Reduced Graphene Oxide Composite Filler

Structure, Piezoresponse, and Physical and Mechanical Properties of Scaffolds Based on Polyhydroxybutyrate with a Magnetite/Reduced Graphene Oxide Composite Filler

Additive Manufacturing of Polymer/Bioactive Glass Scaffolds for Regenerative Medicine: A Review.

Tissue engineering (TE) is a branch of regenerative medicine with enormous potential to regenerate damaged tissues using synthetic grafts such as scaffolds. Polymers and bioactive glasses (BGs) are popular materials for scaffold production because of their tunable properties and ability to interact with the body for effective tissue regeneration. Due to their composition and amorphous structure, BGs possess a significant affinity with the recipient's tissue. Additive manufacturing (AM), a method that allows the creation of complex shapes and internal structures, is a promising approach for scaffold production. However, despite the promising results obtained so far, several challenges remain in the field of TE. One critical area for improvement is tailoring the mechanical properties of scaffolds to meet specific tissue requirements. In addition, achieving improved cell viability and controlled degradation of scaffolds is necessary to ensure successful tissue regeneration. This review provides a critical summary of the potential and limitations of polymer/BG scaffold production via AM covering extrusion-, lithography-, and laser-based 3D-printing techniques. The review highlights the importance of addressing the current challenges in TE to develop effective and reliable strategies for tissue regeneration.

Antibacterial 3D-Printed Silver Nanoparticle/Poly Lactic-Co-Glycolic Acid (PLGA) Scaffolds for Bone Tissue Engineering.

Infectious bone defects present a major challenge in the clinical setting currently. In order to address this issue, it is imperative to explore the development of bone tissue engineering scaffolds that are equipped with both antibacterial and bone regenerative capabilities. In this study, we fabricated antibacterial scaffolds using a silver nanoparticle/poly lactic-co-glycolic acid (AgNP/PLGA) material via a direct ink writing (DIW) 3D printing technique. The scaffolds' microstructure, mechanical properties, and biological attributes were rigorously assessed to determine their fitness for repairing bone defects. The surface pores of the AgNPs/PLGA scaffolds were uniform, and the AgNPs were evenly distributed within the scaffolds, as confirmed via scanning electron microscopy (SEM). Tensile testing confirmed that the addition of AgNPs enhanced the mechanical strength of the scaffolds. The release curves of the silver ions confirmed that the AgNPs/PLGA scaffolds released them continuously after an initial burst. The growth of hydroxyapatite (HAP) was characterized via SEM and X-ray diffraction (XRD). The results showed that HAP was deposited on the scaffolds, and also confirmed that the scaffolds had mixed with the AgNPs. All scaffolds containing AgNPs exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). A cytotoxicity assay using mouse embryo osteoblast precursor cells (MC3T3-E1) showed that the scaffolds had excellent biocompatibility and could be used for repairing bone tissue. The study shows that the AgNPs/PLGA scaffolds have exceptional mechanical properties and biocompatibility, effectively inhibiting the growth of S. aureus and E. coli. These results demonstrate the potential application of 3D-printed AgNPs/PLGA scaffolds in bone tissue engineering.

A Biomimetic Approach Utilizing Pulsatile Perfusion Generates Contractile Vascular Grafts.

Surgical implantation of decellularized cadaveric arteries is routinely used to treat right-sided congenital cardiac lesions. These acellular conduits lack the capacity for somatic growth and are prone to stenosis and calcification, necessitating multiple operations throughout childhood. Islet-1+ cardiovascular progenitor cells (CPCs) have demonstrated the capacity for differentiation into all cell types of the heart and outflow tracts. We hypothesize that CPC seeding of decellularized pulmonary arteries and bioreactor culture under physiologic flow conditions will drive vascular differentiation of CPCs and result in a conduit more suitable for implantation and long-term growth. We began by decellularizing ovine pulmonary arteries and characterizing the composition of the extracellular matrix (ECM). Hemodynamic testing of decellularized vessels in a custom bioreactor was used to define the scaffold mechanical properties over a range of pressures and flow rates. Next, our expanded ovine CPCs were suspended in growth media and injected intramurally into decellularized pulmonary arteries that were subsequently cultured in either static or pulsatile cultures. A combination of immunohistochemistry, real-time polymerase chain reaction (PCR), and tissue bath contraction studies were used to evaluate the bioengineered arteries before transplantation. Pulmonary artery patches from the most favorable culture conditions were then implanted into juvenile sheep to provide proof of concept. Hematoxylin and eosin staining indicated complete removal of cell nuclei (n = 9), whereas double-stranded DNA isolation from tissue homogenates showed 99.1% DNA removal (p < 0.01, n = 4). Furthermore, trichrome and elastin staining verified maintenance of collagen and elastin. Immunohistochemistry and PCR analyses (n = 4 per group) confirmed contractile smooth muscle presence on only our 3-week pulsatile scaffolds via presence of calponin 1 and myosin heavy chain 11. Tissue bath studies demonstrated that smooth muscle contraction generated by our 3-week pulsatile scaffolds (2.23 ± 0.19 g, n = 4) is comparable with native tissue contraction strength (2.78 ± 0.06 g, n = 4). Ovine transplantation confirmed that our graft can be safely implanted, retains contractile smooth muscle cells, and recruits native endothelium. Longer duration of physiologic pulsatile culture drives differentiation of CPCs seeded on ECM conduits toward a mature, contractile phenotype that is maintained for several weeks in vivo. Longer term studies to assess somatic growth potential are needed. Impact statement The current field of vascular transplantation relies on cadaveric and synthetic grafts to treat right-sided congenital cardiac lesions. These grafts do not grow somatically with our patients. This results in multiple reoperations throughout childhood to increase the size of the graft. Our bioengineered alternative demonstrates successful implantation, contractile smooth muscle cells, and a native endothelial layer. This research demonstrates a pilot study confirming the viability of a bioengineered alternative to the current standard of care in the field of vascular transplantation.

Formulation development of collagen/chitosan-based porous scaffolds for skin wounds repair and regeneration

Herein we developed a hydrogel based porous cross-linked scaffold intended for the treatment of chronic skin ulcers. It is made of collagen, the most abundant protein of mammals ECM, and chitosan, a natural polysaccharide endowed with numerous positive cues for wound repair. Different cross-linking methods, namely UV irradiation with the addition of glucose, addition of tannic acid as cross-linking agent and ultrasonication, were employed to prepare a cross-linked hydrogel with a highly interconnected 3D internal structure. The variables considered critical to obtain a suitable system for the envisaged application are the composition of hydrogels, especially the concentration of chitosan, and the concentration ratio between chitosan and collagen. Stable systems, characterized by high porosity, were obtained thanks to the use of freeze-drying process. To assess the influence of the above-mentioned variables on scaffold mechanical properties, a Design of Experiments (DoE) approach was exploited, which resulted in the identification of the best hydrogel composition. In vitro and in vivo assays on a fibroblast model cell line and on a murine model, respectively, demonstrated scaffold biocompatibility, biomimicry, and safety.

The Effect of the Mechanical Properties of the 3D Printed Gelatin/Hyaluronic Acid Scaffolds on hMSCs Differentiation Towards Chondrogenesis.

Tissue engineering, including 3D bioprinting, holds great promise as a therapeutic tool for repairing cartilage defects. Mesenchymal stem cells have the potential to treat various fields due to their ability to differentiate into different cell types. The biomimetic substrate, such as scaffolds and hydrogels, is a crucial factor that affects cell behavior, and the mechanical properties of the substrate have been shown to impact differentiation during incubation. In this study, we examine the effect of the mechanical properties of the 3D printed scaffolds, made using different concentrations of cross-linker, on hMSCs differentiation towards chondrogenesis. The 3D scaffold was fabricated using 3D bioprinting technology with gelatin/hyaluronic acid (HyA) biomaterial ink. Crosslinking was achieved by using different concentrations of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methlymorpholinium chloride n-hydrate (DMTMM), allowing for control of the scaffold's mechanical properties. The printability and stability were also evaluated based on the concentration of DMTMM used. The effects of the gelatin/HyA scaffold on chondrogenic differentiation was analyzed by utilizing various concentrations of DMTMM. The addition of HyA was found to improve the printability and stability of 3D printed gelatin/HyA scaffolds. The mechanical properties of the 3D gelatin/HyA scaffold could be regulated through the use of different concentrations of DMTMM cross-linker. In particular, the use of 0.25mM DMTMM for crosslinking the 3D gelatin/HyA scaffold resulted in enhanced chondrocyte differentiation. The mechanical properties of 3D printed gelatin/HyA scaffolds cross-linked using various concentrations of DMTMM can influence the differentiation of hMSCs into chondrocytes.

Conceptual design of compliant bone scaffolds by full-scale topology optimization

A promising new treatment for large and complex bone defects is to implant specifically designed and additively manufactured synthetic bone scaffolds. Optimizing the scaffold design can potentially improve bone in-growth and prevent under- and over-loading of the adjacent tissue. This study aims to optimize synthetic bone scaffolds over multiple-length scales using the full-scale topology optimization approach, and to assess the effectiveness of this approach as an alternative to the currently used mono- and multi-scale optimization approaches for orthopaedic applications. We present a topology optimization formulation, which is matching the scaffold's mechanical properties to the surrounding tissue in compression. The scaffold's porous structure is tuneable to achieve the desired morphological properties to enhance bone in-growth. The proposed approach is demonstrated in-silico, using PEEK, cortical bone and titanium material properties in a 2D parameter study and on 3D designs. Full-scale topology optimization indicates a design improvement of 81% compared to the multi-scale approach. Furthermore, 3D designs for PEEK and titanium are additively manufactured to test the applicability of the method. With further development, the full-scale topology optimization approach is anticipated to offer a more effective alternative for optimizing orthopaedic structures compared to the currently used multi-scale methods.

Monitoring of freezing patterns within 3D collagen-hydroxyapatite scaffolds using infrared thermography

The importance of cryopreservation in tissue engineering is unceasingly increasing. Preparation, cryopreservation, and storage of tissue-engineered constructs (TECs) at an on-site location offer a convenient way for their clinical application and commercialization. Partial freezing initiated at high sub-zero temperatures using ice-nucleating agents (INAs) has recently been applied in organ cryopreservation. It is anticipated that this freezing technique may be efficient for the preservation of both scaffold mechanical properties and cell viability of TECs. Infrared thermography is an instrumental method to monitor INAs-mediated freezing of various biological entities.In this paper, porous collagen-hydroxyapatite (collagen-HAP) scaffolds were fabricated and characterized as model TECs, whereas infrared thermography was proposed as a method for monitoring the crystallization-related events on their partial freezing down to −25 °C. Intra- and interscaffold latent heat transmission were descriptively evaluated. Nucleation, freezing points as well as the degree of supercooling and duration of crystallization were calculated based on inspection of respective thermographic curves. Special consideration was given to the cryoprotective agent (CPA) composition (Snomax®, crude leaf homogenate (CLH) from Hippophae rhamnoides, dimethyl sulfoxide (Me2SO) and recombinant type-III antifreeze protein (AFP)) and freezing conditions (‘in air’ or ‘in bulk CPA’).For CPAs without ice nucleation activity, thermographic measurements demonstrated that the supercooling was significantly milder in the case of scaffolds present in a CPA solution compared to that without them. This parameter (ΔT, °C) altered with the following tendency: 10 Me2SO (2.90 ± 0.54 (‘scaffold in a bulk CPA’) vs. 7.71 ± 0.43 (‘bulk CPA’, P < 0.0001)) and recombinant type-III AFP, 0.5 mg/ml (2.65 ± 0.59 (‘scaffold in a bulk CPA’) vs. 7.68 ± 0.34 (‘bulk CPA’, P < 0.0001)).At the same time, in CPA solutions with ice nucleation activity the least degree of supercooling and the longest crystallization duration (Δt, min) for scaffolds frozen ‘in air’ were documented for CLH from Hippophae rhamnoides (1.57 ± 0.37 °C and 21.86 ± 2.93 min) compared to Snomax, 5 μg/ml (2.14 ± 0.33 °C and 19.91 ± 4.72 min), respectively).Moreover, when frozen ‘in air’ in CLH from Hippophae rhamnoides, collagen-HAP scaffolds were shown to have the longest ice-liquid equilibrium phase during crystallization and the lowest degree of supercooling followed by alginate core-shell capsules and nanofibrous electrospun fiber mats made of poly ɛ-caprolactone (PCL) and polylactic acid (PLA) (PCL/PLA) blend.The paper offers evidence that infrared thermography provides insightful information for monitoring partial freezing events in TECs when using different freezing containers, CPAs and conditions. This may further TEC-specific cryopreservation with enhanced batch homogeneity and optimization of CPA compositions of natural origin active at warm sub-zero temperatures.

Designing Viscoelastic Gelatin-PEG Macroporous Hybrid Hydrogel with Anisotropic Morphology and Mechanical Properties for Tissue Engineering Application

The mechanical properties of scaffolds play a vital role in regulating key cellular processes in tissue development and regeneration in the field of tissue engineering. Recently, scaffolding material design strategies leverage viscoelasticity to guide stem cells toward specific tissue regeneration. Herein, we designed and developed a viscoelastic Gel-PEG hybrid hydrogel with anisotropic morphology and mechanical properties using a gelatin and functionalized PEG (as a crosslinker) under a benign condition for tissue engineering application. The chemical crosslinking/grafting reaction was mainly involved between epoxide groups of PEG and available functional groups of gelatin. FTIR spectra revealed the hybrid nature of Gel-PEG hydrogel. The hybrid hydrogel showed good swelling behavior (water content &gt; 600%), high porosity and pore interconnectivity suitable for tissue engineering application. Simple unidirectional freezing followed by a freeze-drying technique allowed the creation of structurally stable 3D anisotropic macroporous architecture that showed tissue-like elasticity and was capable of withstanding high deformation (50% strain) without being damaged. The tensile and compressive modulus of Gel-PEG hybrid hydrogel were found to be 0.863 MPa and 0.330 MPa, respectively, which are within the range of normal human articular cartilage. In-depth mechanical characterizations showed that the Gel-PEG hybrid hydrogel possessed natural-tissue-like mechanics such as non-linear and J-shaped stress-strain curves, stress softening effect, high fatigue resistance and stress relaxation response. A month-long hydrolytic degradation test revealed that the hydrogel gradually degraded in a homogeneous manner over time but maintained its structural stability and anisotropic mechanics. Overall, all these interesting features provide a potential opportunity for Gel-PEG hybrid hydrogel as a scaffold in a wide range of tissue engineering applications.

Understanding compressive viscoelastic properties of additively manufactured PLA for bone-mimetic scaffold design.

Bone tissue engineering has been recognized as a promising strategy to repair or replace damaged bone tissues. The mechanical properties of bone scaffolds play a critical role in successful bone regeneration, as it is essential to match the mechanical properties of the scaffold with the surrounding bone tissue. In this study, we investigated the effects of fused deposition modeling (FDM) process parameters, including printing speed, printing temperature, and layer thickness, on the compressive viscoelastic properties of polylactic acid (PLA) scaffolds. The compressive viscoelastic properties of bulk PLA specimens were characterized using a Zhu-Wang-Tang (ZWT) constitutive model under different compressive strain rates. A comprehensive statistical analysis comprising multivariate and univariate analysis of variance (MANOVA and ANOVA) and Tukey's post hoc analysis was utilized to quantify the effect of each FDM parameter on the viscoelastic mechanical properties of the PLA specimens. Subsequently, we fabricated modified face-centered cubic (MFCC) scaffolds using FDM and varied the FDM process parameters to achieve a compressive viscoelastic response that matched the natural trabecular bone tissue. The viscoelastic performance of the MFCC scaffolds was compared with traditional orthogonal cylindrical struts (OCS) scaffolds. Our methodology contributes to the design of bone-mimetic scaffolds with optimized mechanical properties by controlling FDM process parameters.

Fabrication and multiscale modeling of polycaprolactone/amniotic membrane electrospun nanofiber scaffolds for wound healing.

Enhancing the efficiency of cell-based skin tissue engineering (TE) approaches is possible via designing electrospun scaffolds possessing natural materials like amniotic membrane (AM) with wound healing characteristics. Concentrating on this aim, we fabricated innovative polycaprolactone (PCL)/AM scaffolds through the electrospinning process. The manufactured structures were characterized by employing scanning electron microscope (SEM), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, tensile testing, Bradford protein assay, etc. In addition, the mechanical properties of scaffolds were simulated by the multiscale modeling method. As a result of conducting various tests, it was concluded that the uniformity and distribution of fibers decreased with an increase in the amniotic content. Furthermore, PCL-AM scaffolds contained amniotic and PCL characteristic bands. In the case of protein release, greater content of AM led to the release of higher amounts of collagen. Tensile testing revealed that scaffolds' ultimate strength increased when the AM content augmented. The multiscale modeling demonstrated that the scaffold had elastoplastic behavior. In order to assess cellular attachment, viability, and differentiation, human adipose-derived stem cells (ASCs) were seeded on the scaffolds. In this regard, SEM and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays showed significant cellular proliferation and viability on the proposed scaffolds, and these analyses illustrated that higher cell survival and adhesion could be achieved when scaffolds possessed a larger amount of AM. After 21 days of cultivation, particular keratinocyte markers, such as keratin I and involucrin, were identified through utilizing immunofluorescence and real-time polymerase chain reaction (PCR) tests. The markers' expressions were higher in the PCL-AM scaffold with a ratio of 90:10 v v-1 compared with the PCL-epidermal growth factor (EGF) structure. Moreover, the presence of AM in the scaffolds resulted in the keratinogenic differentiation of ASCs even without employing EGF. Consequently, this state-of-the-art experiment suggests that the PCL-AM scaffold can be a promising candidate in skin bioengineering. This study showed that mixing AM with PCL, a widely used polymer, in different concentrations can overcome PCL disadvantages such as high hydrophobicity and low cellular compatibility.

Acoustic Force Elastography Microscopy.

Hydrogel scaffolds have attracted attention to develop cellular therapy and tissue engineering platforms for regenerative medicine applications. Among factors, local mechanical properties of scaffolds drive the functionalities of cell niche. Dynamic mechanical analysis (DMA), the standard method to characterize mechanical properties of hydrogels, restricts development in tissue engineering because the measurement provides a single elasticity value for the sample, requires direct contact, and represents a destructive evaluation preventing longitudinal studies on the same sample. We propose a novel technique, acoustic force elastography microscopy (AFEM), to evaluate elastic properties of tissue engineering scaffolds. AFEM can resolve localized and two-dimensional (2D) elastic properties of both transparent and opaque materials with advantages of being non-contact and non-destructive. Gelatin hydrogels, neat synthetic oligo[poly(ethylene glycol)fumarate] (OPF) scaffolds, OPF hydroxyapatite nanocomposite scaffolds and ex vivo biological tissue were examined with AFEM to evaluate the elastic modulus. These measurements of Young's modulus range from approximately 2 kPa to over 100 kPa were evaluated and are in good agreement with finite element simulations, surface wave measurements, and DMA tests. The AFEM can resolve localized and 2D elastic properties of hydrogels, scaffolds and thin biological tissues. These materials can either be transparent or non-transparent and their evaluation can be done in a non-contact and non-destructive manner, thereby facilitating longitudinal evaluation. AFEM is a promising technique to quantify elastic properties of scaffolds for tissue engineering and will be applied to provide new insights for exploring elastic changes of cell-laden scaffolds for tissue engineering and material science.