3D-printed hydrogels dressings with bioactive borate glass for continuous hydration and treatment of second-degree burns.

Recent advances in additive manufacturing have led to the development of innovative solutions for tissue regeneration. Hydrogel materials have gained significant attention for burn wound treatment in clinical practice among various advanced dressings due to their soothing and moisturizing activity. However, prolonged healing, pain, and traumatic removal due to the lack of long-term wound hydration are some of the challenges in the treatment of second-degree burn wounds. In this study, 3D-printed dressings were fabricated using gelatin, alginate, and bioactive borate glass (BBG) using an extrusion-based bioprinter. After ionic crosslinking, the 3D-printed dressings were characterized for mechanical properties, degradation rate, hydration activity, and in vitro cell viability using human fibroblasts. The results demonstrated that in 3D-printed dressings with 20 wt% BBG, Young's modulus increased by 105%, and 10-day degradation rate decreased by 62%. Addition of BBG prevented the burst release of water from hydrogel dressings and enabled the continuous water release for up to 10 days, which is crucial in treating second-degree burn wounds. 3D-printed hydrogel dressings with BBG showed long-term cell viability that can be a result of the accumulative release of therapeutic ions from BBG particulate. The in vivo wound healing functionality of the dressings was investigated using a rat model with a second-degree burn wound. Our animal study showed that the 3D-printed dressings with BBG exhibited faster wound closure, non-adhesive contact, non-invasive debridement, and non-traumatic dressing removal. Histological analysis suggested that 3D-printed dressings contributed to more uniform re-epithelialization and tissue remodeling compared to the non-printed hydrogels of the same compositions. Critically, 3D-printed dressings with BBG led to significant regeneration of hair follicles compared to the 3D-printed hydrogel, non-printed hydrogel, and the control groups. The superior outcome of the 3D-printed hydrogel-BBG20 dressings can be attributed to the bioactive formulation, which promotes moist wound healing for longer time periods, and the non-adhesive porous texture of the 3D-printed dressings with increased wound-dressing interactions. Our findings provided proof of concept for the synergistic effect of bioactive formulation and the porous texture of the 3D-printed hydrogel dressings incorporated with BBG on continuous water release and, consequently, on second-degree burn wound healing.

3D-Printed Gelatin-Alginate Hydrogel Dressings for Burn Wound Healing: A Comprehensive Study.

Burn wound treatment is still a clinical challenge due to the severity of tissue damage and dehydration. Among various wound dressings, hydrogel materials have gained significant attention for burn wound treatment in clinical practice due to their soothing and moisturizing activity. In this study, 3D-printed dressings were fabricated using clinically relevant hydrogels for deep partial-thickness burn (PTB) wounds. Different ratios of gelatin and alginate mixture were 3D-printed and examined in terms of rheological behavior, shear thinning behavior, mechanical properties, degradation rate, and hydration activity to tune the hydrogel composition for best functionality. The cell-laden dressings were bioprinted to evaluate the effect of the gelatin: alginate ratio on the proliferation and growth of human dermal fibroblasts. The present findings confirm that the higher alginate content is associated with higher viscosity and Young's modulus, while higher gelatin content is associated with faster degradation and higher cell viability. Together, the 3D-printed dressing with 75% gelatin and 25% alginate showed the best tradeoff between mechanical properties, hydration activity, and in vitro biological response. Findings from in vivo test using the most effective dressing showed the positive effect of 3D-printed porous pattern on wound healing, including faster wound closure, regenerated hair follicles, and non-traumatic dressing removal compared to the non-printed hydrogel with the same composition and the standard of care. Results from this research showed that 3D-printed dressings with an adequate gelatin: alginate ratio enhanced wound healing activity for up to 7 days of moisture retention on deep PTB wounds.

3D-printed Biomimetic Bioactive Glass Scaffolds for Bone Regeneration in Rat Calvarial Defects.

The pore geometry of scaffold intended for the use in the bone repair or replacement is one of the most important parameters in bone tissue engineering. It affects not only the mechanical properties of the scaffold but also the amount of bone regeneration after implantation. Scaffolds with five different architectures (cubic, spherical, x, gyroid, and diamond) at different porosities were fabricated with bioactive borate glass using the selective laser sintering (SLS) process. The compressive strength of scaffolds with porosities ranging from 60% to 30% varied from 1.7 to 15.5 MPa. The scaffold's compressive strength decreased significantly (up to 90%) after 1-week immersion in simulated body fluids. Degradation of scaffolds is dependent on porosity, in which the scaffold with the largest surface area has the largest reduction in strength. Scaffolds with traditional cubic architecture and biomimetic diamond architecture were implanted in 4.6 mm diameter full-thickness rat calvarial defects for 6 weeks to evaluate the bone regeneration with or without bone morphogenetic protein 2 (BMP-2). Histological analysis indicated no significant difference in bone formation in the defects treated with the two different architectures. However, the defects treated with the diamond architecture scaffolds had more fibrous tissue formation and thus have the potential for faster bone formation. Overall, the results indicated that borate glass scaffolds fabricated using the SLS process have the potential for bone repair and the addition of BMP-2 significantly improves bone regeneration.

Aluminum Parts Fabricated by Laser-Foil-Printing Additive Manufacturing: Processing, Microstructure, and Mechanical Properties.

Fabrication of dense aluminum (Al-1100) parts (>99.3% of relative density) by our recently developed laser-foil-printing (LFP) additive manufacturing method was investigated as described in this paper. This was achieved by using a laser energy density of 7.0 MW/cm2 to stabilize the melt pool formation and create sufficient penetration depth with 300 µm thickness foil. The highest yield strength (YS) and ultimate tensile strength (UTS) in the LFP-fabricated samples reached 111 ± 8 MPa and 128 ± 3 MPa, respectively, along the laser scanning direction. These samples exhibited greater tensile strength but less ductility compared to annealed Al-1100 samples. Fractographic analysis showed elongated gas pores in the tensile test samples. Strong crystallographic texturing along the solidification direction and dense subgrain boundaries in the LFP-fabricated samples were observed by using the electron backscattered diffraction (EBSD) technique.

Bioprinting with human stem cell-laden alginate-gelatin bioink and bioactive glass for tissue engineering.

Three-dimensional (3D) bioprinting technologies have shown great potential in the fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin (Alg-Gel) hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12 × 12 × 1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alg-Gel composite hydrogel is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate the feasibility of the solvent-based bioprinting process to fabricate 3D cellularized scaffolds with more than 80% viability on day 0. The decrease in viability after 7 days due to glass concentration and static culture conditions is discussed. The feasibility of modifying Alg-Gel with 13-93B3 glass for bioprinting is also investigated, and the results are discussed.

Near-field electrospinning of a polymer/bioactive glass composite to fabricate 3D biomimetic structures.

Bioactive glasses have recently gained attention in tissue engineering and three-dimensional (3D) bioprinting because of their ability to enhance angiogenesis. Some challenges for developing biological tissues with bioactive glasses include incorporation of glass particles and achieving a 3D architecture mimicking natural tissues. In this study, we investigate the fabrication of scaffolds with a polymer/bioactive glass composite using near-field electrospinning (NFES). An overall controlled 3D scaffold with pores, containing random fibers, is created and aimed to provide superior cell proliferation. Highly angiogenic borate bioactive glass (13-93B3) in 20 wt.% is added to polycaprolactone (PCL) to fabricate scaffolds using the NFES technique. Scaffolds measuring 5 mm × 5 mm × 0.2 mm3 in overall dimensions were seeded with human adipose-derived mesenchymal stem cells to investigate the cell viability. The cell viability on PCL and PCL+glass scaffolds fabricated using NFES technique and 3D printing is compared and discussed. The results indicated higher cell proliferation on 3D biomimetic scaffolds fabricated by NFES technique.

Freeform extrusion fabrication of titanium fiber reinforced 13-93 bioactive glass scaffolds.

Although implants made with bioactive glass have shown promising results for bone repair, their application in repairing load-bearing long bone is limited due to their poor mechanical properties in comparison to human bone. This work investigates the freeform extrusion fabrication of bioactive silicate 13-93 glass scaffolds reinforced with titanium (Ti) fibers. A composite paste prepared with 13-93 glass and Ti fibers (~16µm in diameter and lengths varying from ~200µm to ~2 mm) was extruded through a nozzle to fabricate scaffolds (0-90° filament orientation pattern) on a heated plate. The sintered scaffolds measured pore sizes ranging from 400 to 800µm and a porosity of ~50%. Scaffolds with 0.4vol% Ti fibers measured fracture toughness of ~0.8MPam1/2 and a flexural strength of ~15MPa. 13-93 glass scaffolds without Ti fibers had a toughness of ~0.5MPam1/2 and a strength of ~10MPa. The addition of Ti fibers increased the fracture toughness of the scaffolds by ~70% and flexural strength by ~40%. The scaffolds' biocompatibility and their degradation in mechanical properties in vitro were assessed by immersing the scaffolds in a simulated body fluid over a period of one to four weeks.

Freeform extrusion fabrication of titanium fiber reinforced 13-93 bioactive glass scaffolds.

Although implants made with bioactive glass have shown promising results for bone repair, their application in repairing load-bearing long bone is limited due to their poor mechanical properties in comparison to human bone. This work investigates the freeform extrusion fabrication of bioactive silicate 13-93 glass scaffolds reinforced with titanium (Ti) fibers. A composite paste prepared with 13-93 glass and Ti fibers (~16µm in diameter and lengths varying from ~200µm to ~2 mm) was extruded through a nozzle to fabricate scaffolds (0-90° filament orientation pattern) on a heated plate. The sintered scaffolds measured pore sizes ranging from 400 to 800µm and a porosity of ~50%. Scaffolds with 0.4vol% Ti fibers measured fracture toughness of ~0.8MPam1/2 and a flexural strength of ~15MPa. 13-93 glass scaffolds without Ti fibers had a toughness of ~0.5MPam1/2 and a strength of ~10MPa. The addition of Ti fibers increased the fracture toughness of the scaffolds by ~70% and flexural strength by ~40%. The scaffolds' biocompatibility and their degradation in mechanical properties in vitro were assessed by immersing the scaffolds in a simulated body fluid over a period of one to four weeks.

The effects of 3D bioactive glass scaffolds and BMP-2 on bone formation in rat femoral critical size defects and adjacent bones.

Reconstruction of critical size defects in the load-bearing area has long been a challenge in orthopaedics. In the past, we have demonstrated the feasibility of using a biodegradable load-sharing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. For this reason, 13-93 bioactive glass scaffolds with local BMP-2 delivery were investigated in this study for inducing segmental defect repairs in a load-bearing region. Furthermore, a recent review on BMP-2 revealed greater risks in radiculitis, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. We also evaluated the potential side effects of locally delivered BMP-2 on the structures of adjacent bones. Therefore, cylindrical 13-93 glass scaffolds were fabricated by indirect selective laser sintering with side holes on the cylinder filled with dicalcium phosphate dehydrate as a BMP-2 carrier. The scaffolds were implanted into critical size defects created in rat femurs with and without 10 µg of BMP-2. The x-ray and micro-CT results showed that a bridging callus was found as soon as three weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. Degradation of the scaffolds was noted in both groups. Stiffness, peak load and energy to break of the BMP group were all higher than the control group. There was no statistical difference in bone mineral density, bone area and bone mineral content in the tibiae and contralateral femurs of the control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects.

Driving simulator validation of driver behavior with limited safe vantage points for data collection in work zones.

INTRODUCTION: This study is aimed at validating a driving simulator (DS) for the study of driver behavior in work zones. A validation study requires field data collection. For studies conducted in highway work zones, the availability of safe vantage points for data collection at critical locations can be a significant challenge. A validation framework is therefore proposed in this paper, demonstrated using a fixed-based DS that addresses the issue by using a global positioning system (GPS). METHODS: The validation of the DS was conducted using objective and subjective evaluations. The objective validation was divided into qualitative and quantitative evaluations. The DS was validated by comparing the results of simulation with the field data, which were collected using a GPS along the highway and video recordings at specific locations in a work zone. The constructed work zone scenario in the DS was subjectively evaluated with 46 participants. RESULTS: The objective evaluation established the absolute and relative validity of the DS. The mean speeds from the DS data showed excellent agreement with the field data. The subjective evaluation indicated realistic driving experience by the participants. PRACTICAL APPLICATIONS: The use of GPS showed that continuous data collected along the highway can overcome the challenges of unavailability of safe vantage points especially at critical locations. Further, a validated DS can be used for examining driver behavior in complex situations by replicating realistic scenarios.

Effect of material, process parameters, and simulated body fluids on mechanical properties of 13-93 bioactive glass porous constructs made by selective laser sintering.

The effect of particle size distribution, binder content, processing parameters, and sintering schedule on the microstructure and mechanical properties of porous constructs was investigated. The porous constructs were produced by indirect selective laser sintering (SLS) of 13-93 bioactive glass using stearic acid as a polymeric binder. The binder content and d(50) particle size in the feedstock powders were simultaneously reduced from 22 to 12 wt% and from 20 to 11 µm, respectively, to identify the minimum binder content required for the SLS fabrication. An average particle size of ∼16 µm with a binder content of 15 wt% significantly reduced post-processing time and improved mechanical properties. Increasing the laser power and scan speed at the energy density of 1 cal/cm² maintained the feature sharpness of the parts during the fabrication of green parts and could almost double the mechanical properties of the sintered parts. Changes in the heating rates, ranging from 0.1 to 2 °C/min, during the post-processing of the fabricated "green" scaffolds showed that the heating rate significantly affects the densification and mechanical properties of the sintered scaffolds. The compressive strength of the scaffolds manufactured with the optimized parameters varied from 41 MPa, for a scaffold with a porosity of ∼50%, to 157 MPa, for a dense part. The bioactive scaffolds soaked in simulated body fluids for durations up to 6 weeks were used to evaluate the change in mechanical properties in vitro.

Fabrication of 13-93 bioactive glass scaffolds for bone tissue engineering using indirect selective laser sintering.

Bioactive glasses are promising materials for bone scaffolds due to their ability to assist in tissue regeneration. When implanted in vivo, bioactive glasses can convert into hydroxyapatite, the main mineral constituent of human bone, and form a strong bond with the surrounding tissues, thus providing an advantage over polymer scaffold materials. Bone scaffold fabrication using additive manufacturing techniques can provide control over pore interconnectivity during fabrication of the scaffold, which helps in mimicking human trabecular bone. 13-93 glass, a third-generation bioactive material designed to accelerate the body's natural ability to heal itself, was used in the research described herein to fabricate bone scaffolds using the selective laser sintering (SLS) process. 13-93 glass mixed with stearic acid (as the polymer binder) by ball milling was used as the powder feedstock for the SLS machine. The fabricated green scaffolds underwent binder burnout to remove the stearic acid binder and were then sintered at temperatures between 675 °C and 695 °C. The sintered scaffolds had pore sizes ranging from 300 to 800 µm with 50% apparent porosity and an average compressive strength of 20.4 MPa, which is excellent for non-load bearing applications and among the highest reported for an interconnected porous scaffold fabricated with bioactive glasses using the SLS process. The MTT labeling experiment and measurements of MTT formazan formation are evidence that the rough surface of SLS scaffolds provides a cell-friendly surface capable of supporting robust cell growth.

Freeze extrusion fabrication of 13-93 bioactive glass scaffolds for bone repair.

A solid freeform fabrication technique, freeze extrusion fabrication (FEF), was investigated for the creation of three-dimensional bioactive glass (13-93) scaffolds with pre-designed porosity and pore architecture. An aqueous mixture of bioactive glass particles and polymeric additives with a paste-like consistency was extruded through a narrow nozzle, and deposited layer-by-layer in a cold environment according to a computer-aided design (CAD) file. Following sublimation of the ice in a freeze dryer, the construct was heated according to a controlled schedule to burn out the polymeric additives (below ~500°C), and to densify the glass phase at higher temperature (1 h at 700°C). The sintered scaffolds had a grid-like microstructure of interconnected pores, with a porosity of ~50%, pore width of ~300 µm, and dense glass filaments (struts) with a diameter or width of ~300 µm. The scaffolds showed an elastic response during mechanical testing in compression, with an average compressive strength of 140 MPa and an elastic modulus of 5-6 GPa, comparable to the values for human cortical bone. These bioactive glass scaffolds created by the FEF method could have potential application in the repair of load-bearing bones.

Image processing, geometric modeling and data management for development of a virtual bone surgery system.

This paper describes image processing, geometric modeling and data management techniques for the development of a virtual bone surgery system. Image segmentation is used to divide CT scan data into different segments representing various regions of the bone. A region-growing algorithm is used to extract cortical bone and trabecular bone structures systematically and efficiently. Volume modeling is then used to represent the bone geometry based on the CT scan data. Material removal simulation is achieved by continuously performing Boolean subtraction of the surgical tool model from the bone model. A quadtree-based adaptive subdivision technique is developed to handle the large set of data in order to achieve the real-time simulation and visualization required for virtual bone surgery. A Marching Cubes algorithm is used to generate polygonal faces from the volumetric data. Rendering of the generated polygons is performed with the publicly available VTK (Visualization Tool Kit) software. Implementation of the developed techniques consists of developing a virtual bone-drilling software program, which allows the user to manipulate a virtual drill to make holes with the use of a PHANToM device on a bone model derived from real CT scan data.

Modeling and rendering for a virtual bone surgery system.

A virtual bone surgery system is being developed to guide a novice surgeon practicing bone surgery operations, as well as to allow an experienced orthopedic surgeon planning and rehearsing bone surgery procedures. The development of this system involves medical image processing, geometric modeling, graphics rendering, haptic rendering, and auditory rendering. It is implemented with a personal computer and a PHANToM(TM) device capable of providing the position and orientation information of the virtual tool and generating force feedback. This paper presents the techniques we have devised for the development of this surgery simulation system.