Degradation Rate Of Scaffolds Research Articles

A novel 3D-printed scaffold for patient-specific partial breast reconstruction: A prospective, single-arm clinical trial.

e23227 Background: The current scarcity of appropriate breast fillers restricts the availability of breast-conserving surgery for breast cancer patients. The advent of 3D printing technology has introduced novel possibilities for breast reconstruction by fabricating the patient-specific and custom-designed medical products in three dimensions. Methods: We performed a prospective, single-arm clinical trial. The trial population included woman aged between 18 and 60 years with histologically confirmed breast cancer. (Primary) tumors with a size greater than 1.0 cm and less than 8.0 cm, or those presenting as multiple diffuse lesions limited to a single quadrant, preclude the feasibility of traditional breast-conserving surgery. Patients were assigned to receive the patient-specific 3D-printed scaffolds transplantation surgery. Degradation of 3D-printed scaffold, cosmetic outcomes, complications, satisfaction of patients was assessed. Results: Between August of 2016 and August of 2023, 26 patients received partial breast reconstruction using 3D-printed patient-specific scaffolds. The median follow-up was 58.9 months (range, 29 to 88 months). Patients who received partial breast reconstruction with 3D-printed scaffolds have natural-looking and symmetrical breasts after surgery. One year after operation, mild depression at the implantation site was observed in four patients (15.4%). This number increased to seven (26.9%) after two years of surgery. No flap necrosis or ischemia was observed in the nipple and areola area in all patients. Hematoxylin & Eosin showed that fibrous connective tissue, fibroblast cells and blood vessels were observed inside/around the scaffold after one year of surgery. The average degradation rate of 3D-printed scaffolds is 54.07% at 12 months, 74.48% at 24 months, 86.94% at 36 months,87.36% at 48 months, and 92.76% at 60 months. The breast satisfaction score rating by Breast-q scale is 68.5±15.7 at 6 months, 65.4±14.2 at 12 months, and 62.8±15.9 at 24 months. Conclusions: This is the first report of 3D-printed biodegradable scaffolds for breast reconstruction. Partial breast reconstruction using a 3D-printed scaffold presents a viable alternative for breast cancer patients who are not suitable candidates for conventional breast-conserving surgery, yielding promising outcomes. Clinical trial information: NCT03348293 .

Extrusion 3D-printed tricalcium phosphate-polycaprolactone biocomposites for quercetin-KCl delivery in bone tissue engineering.

Critical-sized bone defects pose a significant challenge in advanced healthcare due to limited bone tissue regenerative capacity. The complex interplay of numerous overlapping variables hinders the development of multifunctional biocomposites. Phytochemicals show promise in promoting bone growth, but their dose-dependent nature and physicochemical properties halt clinical use. To develop a comprehensive solution, a 3D-printed (3DP) extrusion-based tricalcium phosphate-polycaprolactone (TCP-PCL) scaffold is augmented with quercetin and potassium chloride (KCl). This composite material demonstrates a compressive strength of 30 MPa showing promising stability for low load-bearing applications. Quercetin release from the scaffold follows a biphasic pattern that persists for up to 28 days, driven via diffusion-mediated kinetics. The incorporation of KCl allows for tunable degradation rates of scaffolds and prevents the initial rapid release. Functionalization of scaffolds facilitates the attachment and proliferation of human fetal osteoblasts (hfOB), resulting in a 2.1-fold increase in cell viability. Treated scaffolds exhibit a 3-fold reduction in osteosarcoma (MG-63) cell viability as compared to untreated substrates. Ruptured cell morphology and decreased mitochondrial membrane potential indicate the antitumorigenic potential. Scaffolds loaded with quercetin and quercetin-KCl (Q-KCl) demonstrate 76% and 89% reduction in bacterial colonies of Staphylococcus aureus, respectively. This study provides valuable insights as a promising strategy for bone tissue engineering (BTE) in orthopedic repair.

PHASE SEPARATION AND PARTICULATE LEACHING INTEGRATED 3D PRINTING OF POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING APPLICATIONS

Conventional 3D printing by itself is incapable of creating pores on a micro scale within deposited filaments throughout 3D scaffolds. These pores and hence larger surface areas are needed for cells to be adhered, proliferated, and differentiated. The aim of this work was to fabricate 3D polycaprolactone (PCL) scaffolds with internal multiscale porosity by using two different 3D printing techniques (ink/pellet of polymer-salt composite in low/high temperature printing) combined with salt leaching to improve cell adhesion, and cell proliferation besides to change degradation rate of PCL scaffolds:1. Non-solvent phase separation integrated 3D printing of polymer-salt inks with various salt content (i.e., low temperature ink-based printing, LT).2. FDM printing of composite polymer-salt pellets which will be obtained by casting and evaporating of prepared ink (i.e., high temperature composite-pellet-based printing, HT).Further, the two approaches were followed by post salt leaching. Stem cells were able to attach on the surface and grow up to 14 days based on increasing cellular activities.

Development and characterization of antibacterial 3D porous hydroxyapatite-gelatin-PVA scaffolds containing zinc oxide nanoparticles

There is still a need to develop hydroxyapatite (HAp)/gelatin-based porous scaffolds to provide a hybrid system with structural and biochemical properties equivalent to those of bone. Here, we fabricated and characterized 3D hybrid scaffolds composed of HAp nanoparticles synthesized in situ in gelatin and PVA solutions and loaded with combustionally synthesized (10 wt%) zinc oxide nanoparticles (ZnO NPs) to ensure their homogeneous embedding in the polymer matrices. The phase analysis, composition, morphological and microstructural properties of ZnO NPs and freeze-dried hybrid scaffolds were studied. The compressive strength, porosity, swelling capacity, degradation rate, and antibacterial activity of the hybrid scaffolds were measured. The fabricated 3D scaffolds showed high porosity of up to 78 % with a pore size of about 50–300 μm, good mechanical strength in the range of about 55 kPa, high swelling capacity of up to 505 %, and long-term degradation rate of about 22–25 % for up to 35 days. ZnO NPs have a pure phase and a quasi-spherical shape with a size of about 78 ± 25 nm structure and there are no significant differences between the physicochemical properties of ZnO-free scaffolds and ZnO-loaded scaffolds. Incorporation of ZnO NPs into the scaffolds enhanced their antibacterial response against pathogenic Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This work provides advanced 3D porous hybrid bone scaffolds with favorable mechanical performance and antibacterial activity for bone repair and regeneration.

Physically cross-linked chitosan gel with tunable mechanics and biodegradability for tissue engineering scaffold

Chitosan, a cationic polysaccharide, exhibits promising potential for tissue engineering applications. However, the poor mechanical properties and rapid biodegradation have been the major limitations for its applications. In this work, an effective strategy was proposed to optimize the mechanical performance and degradation rate of chitosan gel scaffolds by regulating the water content. Physical chitosan hydrogel (HG, with 93.57 % water) was prepared by temperature-controlled cross-linking, followed by dehydration to obtain xerogel (XG, with 2.84 % water) and rehydration to produce wet gel (WG, with 56.06 % water). During this process, changes of water content significantly influenced the water existence state, hydrogen bonding, and the chain entanglements of chitosan in the gel network. The mechanical compression results showed that the chitosan gel scaffolds exhibited tunable compressive strength (0.3128–139 MPa) and compressive modulus (0.2408–1094 MPa). XG could support weights exceeding 65,000 times its own mass while maintaining structural stability. Furthermore, in vitro and in vivo experiments demonstrated that XG and WG exhibited better biocompatibility and resistance to biodegradation compared with HG. Overall, this work contributes to the design and optimization of chitosan scaffolds without additional chemical crosslinkers, which has potential in tissue engineering and further clinical translation.

3D printed PLGA/MgO/PDA composite scaffold by low-temperature deposition manufacturing for bone tissue engineering applications

IntroductionBones are easily damaged. Biomimetic scaffolds are involved in tissue engineering. This study explored polydopamine (PDA)-coated poly lactic-co-glycolic acid (PLGA)-magnesium oxide (MgO) scaffold properties and its effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. MethodsPLGA/MgO scaffolds were prepared by low-temperature 3D printing technology and PDA coatings were prepared by immersion method. Scaffold structure was observed by scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS), fourier transform infrared spectrometer (FTIR). Scaffold hydrophilicity, compressive/elastic modulus, and degradation rates were analyzed by water contact angle measurement, mechanical tests, and simulated-body fluid immersion. Rat BMSCs were cultured in scaffold extract. Cell activity on days 1, 3, and 7 was detected by MTT. Cells were induced by osteogenic differentiation, followed by evaluation of alkaline phosphatase (ALP) activity on days 3, 7, and 14 of induction and Osteocalcin, Osteocalcin, and Collagen I expressions. ResultsThe prepared PLGA/MgO scaffolds had dense microparticles. With the increase of MgO contents, the hydrophilicity was enhanced, scaffold degradation rate was accelerated, magnesium ion release rate and scaffold extract pH value were increased, and cytotoxicity was less when magnesium mass ratio was less than 10%. Compared with other scaffolds, compressive and elastic modulus of PLGA/MgO (10%) scaffolds were increased; BMSCs incubated with PLGA/MgO (10%) scaffold extract had higher ALP activity and Osteocalcin, Osteopontin, and Collagen I expressions. PDA coating was prepared in PLGA/MgO (10%) scaffolds and the mechanical properties were not affected. PLGA/MgO (10%)/PDA scaffolds had better hydrophilicity and biocompatibility and promoted BMSC osteogenic differentiation. ConclusionLow-temperature 3D printing PLGA/MgO (10%)/PDA scaffolds had good hydrophilicity and biocompatibility, and were conducive to BMSC osteogenic differentiation.

A silk fibroin scaffold that accelerates both biodegradation and cell proliferation by incorporating sericin

When 3D silk fibroin scaffolds are used for the regeneration of soft tissues with fast regeneration rates, such as skin dermis, one concern is to accelerate the biodegradation of scaffolds and to match the degradation rate of scaffolds with the regeneration rate of tissues. In this study, sericin was incorporated into 3D silk fibroin scaffolds through crosslinking and followed by freeze-drying. The effects of incorporating sericin on the pore wall microstructure within the scaffolds, the biodegradability of scaffolds and cell proliferation within scaffolds were investigated. It was found that a large number of secondary pores and nanoscale particles were generated on the pore walls within the scaffolds due to the incorporation of sericin and that the number of secondary pores and the size of the particles increased with increasing sericin proportion. The results of in vitro biodegradation and coculture with human umbilical vein vascular endothelial cells demonstrated that the incorporation of sericin not only significantly accelerated the degradation of 3D silk fibroin scaffolds, but also promoted cell adhesion and proliferation. The secondary pores and particles generated on the pore walls inside the fibroin/sericin hybrid scaffolds had a positive contribution to promoting cell adhesion and proliferation. This study provides a biocompatible method for the modification of silk fibroin scaffolds, which can not only accelerate the biodegradation of the scaffold but also promote the adhesion and proliferation of seeded cells.

Novel barium-doped-baghdadite incorporated PHBV-PCL composite fibrous scaffolds for bone tissue engineering

Bioceramic/polymer composites have dragged a lot of attention for treating hard tissue damage in recent years. In this study, we synthesized barium-doped baghdadite (Ba-BAG), as a novel bioceramic, and later developed fibrous composite poly (hydroxybutyrate) co (hydroxyvalerate)- polycaprolactone (PHBV-PCL) scaffolds containing different amounts of baghdadite (BAG) and Ba-BAG, intended to be used in bone regeneration. Our results demonstrated that BAG and Ba-doped BAG powders were synthesized successfully using the sol-gel method and their microstructural, physicochemical, and cytotoxical properties results were evaluated. In the following, PHBV/PCL composite scaffolds containing different amounts of BAG and Ba-BAG (1, 3, and 5 wt%) were produced by the wet electrospinning method. The porosity of scaffolds decreased from 78% to 72% in Ba-BAG-incorporated PHBV/PCL scaffolds. The compressive strength of the scaffolds was between 4.69 and 9.28 kPa, which was increased to their maximum values in the scaffolds with Ba-BAG. The presence of BAG and Ba-BAG in the polymer scaffolds resulted in increasing bioactivity, and it was introduced as a suitable way to control the degradation rate of scaffolds. The presence of the BAG component was a major reason for higher cell proliferation in reinforced PHBV/PCL polymeric scaffolds, while Ba existence played its influential role in the higher osteogenic activity of cells on Ba-BAG incorporated PHBV/PCL scaffolds. Thus, the incorporation of Ba-BAG bioceramic materials into the structure of polymeric PHBV/PCL scaffolds promoted their various properties, and allow these scaffolds to be used as promising candidates in bone tissue engineering applications.

In vitro degradation of fibrous bilayer poly-L-lactic acid scaffolds

Polymer degradation and mechanical properties are of paramount importance in tissue engineering. The degradation rate of polymeric scaffolds is influenced by several important material and environmental factors. In particular, the mechanical support provided by the scaffold to the surrounding tissue during tissue regeneration is critical for that it directly impacts the cell behavior through mechanical signals sensed by mechanoreceptors on the cell surface. Consequently, the principal objective of the present study was to investigate the degradation behavior of electrospun poly-L-lactic acid (PLLA) bilayer microfibrous scaffolds in pH-neutral medium. Changes in the morphology, molecular weight, crystallinity, mass loss, and thermomechanical properties of the scaffolds over an extended period were studied by scanning electron microscopy, differential scanning calorimetry, gel permeation chromatography, and tensile testing. An interplay between chain scission and orderly chain rearrangement in the polymer scaffold commenced during degradation, leading to the decrease of the molecular weight and stiffness, a constant mass loss, and an increase in crystallinity, tensile strength, and glass transition temperature, with virtually constant yield strength and melting temperature. The unchanged structure morphology and adequate matrix stiffness after prolonged degradation illuminated the potential of the bilayer PLLA scaffolds for tissue engineering and drug delivery applications. Nonetheless, modifications to the scaffold structure or surface may be required to accordingly tune the degradation rate in these applications. The experimental methodology introduced in this study can be extended to potentially investigate material degradation in other fields, such as agriculture, packaging, and disposable products.

Improving physio-mechanical and biological properties of 3D-printed PLA scaffolds via in-situ argon cold plasma treatment

As a bone tissue engineering material, polylactic acid (PLA) has received significant attention and interest due to its ease of processing and biocompatibility. However, its insufficient mechanical properties and poor wettability are two major drawbacks that limit its extensive use. For this purpose, the present study uses in-situ cold argon plasma treatment coupled with a fused deposition modeling printer to enhance the physio-mechanical and biological behavior of 3D-printed PLA scaffolds. Following plasma treatment, field emission scanning electron microscopy images indicated that the surface of the modified scaffold became rough, and the interlayer bonding was enhanced. This resulted in an improvement in the tensile properties of samples printed in the X, Y, and Z directions, with the enhancement being more significant in the Z direction. Additionally, the root mean square value of PLA scaffolds increased (up to 70-fold) after plasma treatment. X-ray photoelectron spectroscopy analysis demonstrated that the plasma technique increased the intensity of oxygen-containing bonds, thereby reducing the water contact angle from 92.5° to 42.1°. The in-vitro degradation study also demonstrated that argon plasma treatment resulted in a 77% increase in PLA scaffold degradation rate. Furthermore, the modified scaffold improved the viability, attachment, and proliferation of human adipose-derived stem cells. These findings suggest that in-situ argon plasma treatment may be a facile and effective method for improving the properties of 3D-printed parts for bone tissue engineering and other applications.

Degradation behavior of 2D auxetic structure with biodegradable polymer under mechanical stress

Coronary heart disease is serious harm to human health. Vascular scaffold implantation is the main treatment. Biodegradable polymers are widely used in vascular scaffolds for good biodegradability and biocompatibility. However, whether the mechanical properties and radial expansion ability can successfully implant the scaffold without acute elastic retraction remains to be further studied. Because of the unique deformation mechanism, shear resistance, and resilience, auxetic structures can effectively avoid the restenosis of degraded vascular scaffolds. Firstly, the plane isotropic and plane anisotropic auxetic structural scaffolds were designed. The control structures (traditional structures) scaffolds were taken as the contrast. PCL was used to prepare the vascular auxetic by 3D printing. The printing parameters of fused deposition 3D printing, such as printing temperature, printing speed, and printing pressure, were studied to determine the optimal printing parameters of PCL. A self-assembled cyclic tensile stress loading device was used to investigate the degradation behavior of different scaffolds under different sizes of cyclic tensile stress, such as surface morphology, pH changes, mass loss rate, and mechanical properties. The increase of stress, surface roughness, and mass loss rate of the scaffolds all showed an increasing trend. pH gradually decreased from the fifth week, and the decrease was proportional to the stress. A large level of stress loading intensifies the decline of elastic modulus and the ultimate strength of the scaffold. In conclusion, the increase of periodic tensile stress will accelerate the degradation of scaffolds, and the degradation behavior of scaffolds with different configurations is different. The degradation rate of dilatant scaffolds was higher than that of control scaffolds, and the degradation rate of anisotropic auxetic scaffolds was higher than that of isotropic auxetic scaffolds, which provides a theoretical reference for the application of auxetic structure in the degradation of vascular scaffolds.

A tailored hydroxyapatite/magnesium silicate 3D composite scaffold: Mechanical, degradation, and bioactivity properties

Today, hydroxyapatite (HA)-based composite scaffolds are widely studied, but there is a lack of a doping method that can simultaneously improve the mechanical strength, degradation rate, and bioactivity of HA scaffolds. In this paper, the amorphous magnesium silicate (MS) with a low melting point is selected as the doping phase of HA. The hydroxyapatite/magnesium silicate composite was fabricated using photocuring technology. In addition, at high temperatures, ionic substitution can occur between the magnesium silicate glass phase and the HA lattice. Therefore, a new phase with a pinning effect can be obtained at the grain boundary and the magnesium silicate can further improve the biocompatibility of HA scaffolds. In the sintering process, the magnesium silicate was melted to a liquid state, and then the sintering temperature of the scaffold was reduced for grain refinement. The morphological analysis shows that MS doping is an important factor for grain refinement, which has been reduced from 12 μm to 6 μm. Furthermore, the formation of new diopside and whitlockite phases with a pinning effect has been observed at the grain boundaries. Specifically, the compressive stress of the composite scaffold is increased by 59.15% compared to the pure HA scaffold. However, the soaking and cell experimental findings show that the composite scaffold has a better degradation rate, cell activity, and bone induction. Finally, this study found that a composite scaffold with improved mechanical strength, degradation performance, and biocompatibility can be obtained with the addition of magnesium silicate as the doping phase of HA with 30 wt% of.

Combined Effects of HA Concentration and Unit Cell Geometry on the Biomechanical Behavior of PCL/HA Scaffold for Tissue Engineering Applications Produced by LPBF.

This experimental study aims at filling the gap in the literature concerning the combined effects of hydroxyapatite (HA) concentration and elementary unit cell geometry on the biomechanical performances of additively manufactured polycaprolactone/hydroxyapatite (PCL/HA) scaffolds for tissue engineering applications. Scaffolds produced by laser powder bed fusion (LPBF) with diamond (DO) and rhombic dodecahedron (RD) elementary unit cells and HA concentrations of 5, 30 and 50 wt.% were subjected to structural, mechanical and biological characterization to investigate the biomechanical and degradative behavior from the perspective of bone tissue regeneration. Haralick's features describing surface pattern, correlation between micro- and macro-structural properties and human mesenchymal stem cell (hMSC) viability and proliferation have been considered. Experimental results showed that HA has negative influence on scaffold compaction under compression, while on the contrary it has a positive effect on hMSC adhesion. The unit cell geometry influences the mechanical response in the plastic regime and also has an effect on the cell proliferation. Finally, both HA concentration and elementary unit cell geometry affect the scaffold elastic deformation behavior as well as the amount of micro-porosity which, in turn, influences the scaffold degradation rate.

Synergistic intrafibrillar/extrafibrillar mineralization of collagen fibrils and scaffolds enhanced by introducing polyacrylamide to PILP for osteogenic differentiation

AbstractMineralization can help improve the mechanical properties and degradation rates of collagen scaffolds while ensuring good biocompatibility, thereby providing a suitable microenvironment for osteogenic differentiation. Intrafibrillar/extrafibrillar mineralization of collagen is promoted by polymer‐induced liquid precursors (PILP). In this study, polyacrylamide (PAM) was introduced to PILP which synergistically mineralized collagen scaffold intrafibrillarly and extrafibrillarly. PAM and polyacrylic acid (PAA) can stabilize the amorphous calcium phosphate (ACP), to form a PILP of PAM and PAA/ACP. As a control, another scaffold material was formed using the conventional mineralization method, that is, soaking collagen in a simulated body fluid. Collagen mineralization was characterized using SEM and TEM. After 7 days of mineralization with PILP, intrafibrillar crystallization of collagen was significantly higher than that in the control group, and the stiffness and modulus of this scaffold material significantly increased. Cellular experiment results indicated that the PILP‐mineralized collagen scaffold was biocompatible and promoted the osteogenic differentiation of MC3T3‐E1 pre‐osteoblasts. Biomimetic mineralization by PILP will assist the fabrication of mineralized collagen scaffold for bone repair applications.

3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair.

Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.

Optical coherence tomography for in vivo longitudinal monitoring of artificial dermal scaffold.

Artificial dermal scaffold (ADS) has undergone rapid development and been increasingly used for treating skin wound in clinics due to its good biocompatibility, controllable degradation, and low risk of disease infection. To obtain good treatment efficacy, ADS needs to be monitored longitudinally during the treatment process. For example, scaffold-tissue fit, cell in-growth, vascular regeneration, and scaffold degradation are the key properties to be inspected. However, to date, there are no effective, real-time, and noninvasive techniques to meet the requirement of the scaffold monitoring above. In this study, we propose to use optical coherence tomography (OCT) to monitor ADS in vivo through three-dimensional imaging. A swept source OCT system with a handheld probe was developed for in vivo skin imaging. Moreover, a cell in-growth, vascular regeneration, and scaffold degradation rate (IRDR) was defined with the volume reduction rate of the scaffold's collagen sponge layer. To measure the IRDR, a semiautomatic image segmentation algorithm was designed based on U-Net to segment the collagen sponge layer of the scaffold from OCT images. The results show that the scaffold-tissue fit can be clearly visualized under OCT imaging. The IRDR can be computed based on the volume of the segmented collagen sponge layer. It is observed that the IRDR appeared to a linear function of the time and in addition, the IRDR varied among different skin parts. Overall, it can be concluded that OCT has a good potential to monitor ADS in vivo. This can help guide the clinicians to control the treatment with ADS to improve the therapy.

Angiogenic Modification of Microfibrous Polycaprolactone by pCMV-VEGF165 Plasmid Promotes Local Vascular Growth after Implantation in Rats.

Insufficient vascular growth in the area of artificial-material implantation contributes to ischemia, fibrosis, the development of bacterial infections, and tissue necrosis around the graft. The purpose of this study was to evaluate angiogenesis after implantation of polycaprolactone microfiber scaffolds modified by a pCMV-VEGF165-plasmid in rats. Influence of vascularization on scaffold degradation was also examined. We investigated flat microfibrous scaffolds obtained by electrospinning polycaprolactone with incorporation of the pCMV-VEGF-165 plasmid into the microfibers at concentrations of 0.005 ng of plasmid per 1 mg of polycaprolactone (0.005 ng/mg) (LCGroup) and 0.05 ng/mg (HCGroup). The samples were subcutaneously implanted in the interscapular area of rats. On days 7, 16, 33, 46, and 64, the scaffolds were removed, and a histological study with a morphometric evaluation of the density and diameter of the vessels and microfiber diameter was performed. The number of vessels was increased in all groups, as well as the resorption of the scaffold. On day 33, the vascular density in the HCGroup was 42% higher compared to the control group (p = 0.0344). The dose-dependent effect of the pCMV-VEGF165-plasmid was confirmed by enhanced angiogenesis in the HCGroup compared to the LCGroup on day 33 (p-value = 0.0259). We did not find a statistically significant correlation between scaffold degradation rate and vessel growth (the Pearson correlation coefficient was ρ = 0.20, p-value = 0.6134). Functionalization of polycaprolactone by incorporation of the pCMV-VEGF165 plasmid provided improved vascularization within 33 days after implantation, however, vessel growth did not seem to correlate with scaffold degradation rate.

3D-printed PLA-Gr-Mg composite scaffolds for bone tissue engineering applications

3D porous PLA-graphite composite scaffolds are recently introduced as promising candidates in tissue engineering practices owing to their significantly enhanced mechanical strength in comparison with pure PLA. However, they mainly suffer from low degradation rate as well as undesirable hydrophobic surface. In this regard and to address such challenges, Mg particles, as one of the lightest metallic fillers, were added to PLA-graphite scaffolds via the fused deposition modeling (FDM) technique. The obtained results indicated that introduction of 1 wt% Mg inhibited polymeric chain mobility of PLA, and hence, increased the glass transition temperature. Also, Mg particles behaved as nucleating agents, thus crystallization temperature was decreased. Compression and tensile tests demonstrated an enhanced trend in strength with the incorporation of Mg. Notably, the hydrophobic surface of PLA-graphite scaffold changed to a hydrophilic surface with the addition of Mg, which also led to a higher degradation rate of Mg-incorporated PLA-graphite composite scaffolds. The obtained results indicated the beneficial effects of Mg in tackling the challenges of PLA-graphite scaffolds for bone tissue applications.

An Injectable Enzymatically Crosslinked and Mechanically Tunable Silk Fibroin/Chondroitin Sulfate Chondro‐Inductive Hydrogel

AbstractAn injectable hybrid hydrogel is synthesized, comprising silk fibroin (SF) and chondroitin sulfate (CS) through di‐tyrosine formation bond of SF chains. CS and SF are reported with excellent biocompatibility as tissue engineering scaffolds. Nonetheless, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate articular cartilage. As CS is one of the cartilage extracellular matrix (ECM) components, it has the potential to enhance the biological activity of SF‐based hydrogel in terms of cartilage repair. Therefore, altering the CS concentrations (i.e., 0 wt%, 0.25 wt%, 0.5 wt%, 1 wt%, and 2 wt%), which are interpenetrated between SF β‐sheets and chains, can potentially adjust the physical, chemical, and mechanical features of these hybrid hydrogels. The formation of β‐sheets by 30 days of immersion in de‐ionized (DI) water can improve the compression strength of the SF/CS hybrid hydrogels in comparison with the same SF/CS hybrid hydrogels in the dried state. Biological investigation and observation depicts proper cell attachment, proliferation and cell viability for C28/I2 cells. Gene expression of sex‐determining region YBox 9 (SOX9), Collagen II α1, and Aggrecan (AGG) exhibits positive C3H10T1/2 growth and expression of cartilage‐specific genes in the 0.25 wt% and 0.5 wt% SF/CS hydrogels.

3D-printed magnesium-doped wollastonite/nano-hydroxyapatite bioceramic scaffolds with high strength and anti-tumor property

It is still a major challenge to remove tumor cells and fill bone defects after tumor resection. Combined with the 3D printing technology, the composite bioceramics scaffolds were fabricated with interconnected porous magnesium-doped wollastonite (CSi-Mg) scaffolds as the architecture and nano-hydroxyapatite (n-HA) as the surface. The influence of manufacturing process on the n-HA layer thickness and degradation performance, biological performance and anti-tumor performance of the composite scaffolds were investigated. The n-HA surface layer could effectively retard the degradation rate of CSi-Mg scaffolds and maintain high mechanical strength (over 90 MPa) after immersion in simulated body fluid for 3 weeks. Meanwhile, CSi-Mg/n-HA3 scaffold induced about 50 % of cell death for human osteosarcoma cells (MG-63) in vitro. CSi-Mg/n-HAx (x = 1, 3) scaffolds could improve the osteogenic performance of Rat BMSC. These findings demonstrate that the bioceramic composite scaffold with high strength, good osteogenic performance and anti-tumor performance is promising for the treatment of tissue injury after resection of osteosarcoma.