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1.
Sci Rep ; 14(1): 17764, 2024 08 01.
Article in English | MEDLINE | ID: mdl-39085375

ABSTRACT

Robotic 3D bioprinting is a rapidly advancing technology with applications in organ fabrication, tissue restoration, and pharmaceutical testing. While the stepwise generation of organs characterizes bioprinting, challenges such as non-linear material behavior, layer shifting, and trajectory tracking are common in freeform reversible embedding of suspended hydrogels (FRESH) bioprinting, leading to imperfections in complex organ construction. To overcome these limitations, we propose a computer vision-based strategy to identify discrepancies between printed filaments and the reference robot path. Employing error compensation techniques, we generate an adjusted reference path, enhancing robotic 3D bioprinting by adapting the robot path based on vision system data. Experimental assessments confirm the reliability and agility of our vision-based robotic 3D bioprinting approach, showcasing precision in fabricating human blood vessel segments through case studies. Significantly, it minimizes the printing layer width disparity to just 0.15 mm compared to the 0.6 mm in traditional methods, and it decreases the average error for curved filaments to 7.0 mm2 from the previous 12.7 mm2 in conventional printing. While these results underscore the significant potential of our innovation in creating precise biomimetic constructs, further investigation is necessary to tackle challenges such as accurately distinguishing closely stacked layers using a vision system, especially under varying lighting conditions. These limitations, coupled with issues of computational complexity and scalability in larger-scale bioprinting, emphasize the importance of enhancing the reliability of the vision-based approach across various conditions. Nonetheless, our innovation demonstrates substantial promise in creating precise biomimetic constructs and paves the way for future advancements in vision-guided robotic bioprinting, including the integration of multi-material printing techniques to enhance versatility.


Subject(s)
Bioprinting , Printing, Three-Dimensional , Robotics , Bioprinting/methods , Robotics/methods , Robotics/instrumentation , Humans , Tissue Engineering/methods , Hydrogels/chemistry
2.
Biomater Adv ; 161: 213885, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38743993

ABSTRACT

Essential organs, such as the heart and liver, contain a unique porous network that allows oxygen and nutrients to be exchanged, with distinct random to ordered regions displaying varying degrees of strength. A novel technique, referred to here as flow-induced lithography, was developed. This technique generates tunable anisotropic three-dimensional (3D) structures. The ink for this bioprinting technique was made of titanium dioxide nanorods (Ti) and kaolinite nanoclay (KLT) dispersed in a GelMA/PEGDA polymeric suspension. By controlling the flow rate, aligned particle microstructures were achieved in the suspensions. The application of UV light to trigger the polymerization of the photoactive prepolymer freezes the oriented particles in the polymer network. Because the viability test was successful in shearing suspensions containing cells, the flow-induced lithography technique can be used with both acellular scaffolds and cell-laden structures. Fabricated hydrogels show outstanding mechanical properties resembling human tissues, as well as significant cell viability (> 95 %) over one week. As a result of this technique and the introduction of bio-ink, a novel approach has been pioneered for developing anisotropic tissue implants utilizing low-viscosity biomaterials.


Subject(s)
Hydrogels , Printing, Three-Dimensional , Stereolithography , Tissue Scaffolds , Hydrogels/chemistry , Tissue Scaffolds/chemistry , Anisotropy , Humans , Titanium/chemistry , Tissue Engineering/methods , Cell Survival , Bioprinting/methods
3.
Biotechnol Bioeng ; 121(2): 507-523, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37905703

ABSTRACT

Bacterial adhesion and biofilm formation on surfaces pose a significant risk of microbial contamination and chronic diseases, leading to potential health complications. To mitigate this concern, the implementation of antibacterial coatings becomes paramount in reducing pathogen propagation on contaminated surfaces. To address this requirement, our study focuses on developing cost-effective and sustainable methods using polymer composite coatings. Copper and titanium dioxide nanoparticles were used to assess their active antimicrobial functions. After coating the surface with nanoparticles, four different combinations of two postprocessing treatments were performed. Intense pulsed light was utilized to sinter the coatings further, and plasma etching was applied to manipulate the physical properties of the nanocomposite-coated sheet surface. Bacterial viability was comparatively analyzed at four different time points (0, 30, 60, and 120 min) upon contact with the nanocomposite coatings. The samples with nanoparticle coatings and postprocessing treatments showed an above-average 84.82% mortality rate at 30 min and an average of 89.77% mortality rate at 120 min of contact. In contrast, the control sample, without nanoparticle coatings and postprocessing treatments, showed a 95% microbe viability after 120 min of contact. Through this study, we gained critical insights into effective strategies for preventing the spread of microorganisms on high-touch surfaces, thereby contributing to the advancement of sustainable antimicrobial coatings.


Subject(s)
Anti-Infective Agents , Nanocomposites , Nanoparticles , Anti-Bacterial Agents/pharmacology , Polymers , Coated Materials, Biocompatible/pharmacology , Titanium
4.
J Mech Behav Biomed Mater ; 150: 106285, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38088008

ABSTRACT

Multifunctional bio-adhesives with tunable mechanical properties are obtained by controlling the orientation of anisotropic particles in a blend of fast-curing hydrogel with an imposed capillary flow. The suspensions' microstructural evolution was monitored by the small-angle light scattering (SALS) method during flow up to the critical Péclet number (Pe≈1) necessary for particle orientation and hydrogel crosslinking. The multifunctional bio-adhesives were obtained by combining flow and UV light exposure for rapid photo-curing of PEGDA medium and freezing titania rods' ordered microstructures. Blending the low- and high-molecular weight of PEGDA polymer improved the mechanical properties of the final hydrogel. All the hydrogel samples were non-cytotoxic up to 72 h after cell culturing. The system shows rapid blood hemostasis and promotes adhesive and cohesive strength matching targeted tissue properties with an applicating methodology compatible with surgical conditions. The developed SALS approach to optimize nanoparticles' microstructures in bio-adhesive applies to virtually any optically transparent nanocomposite and any type of anisotropic nanoparticles. As such, this method enables rational design of bio-adhesives with enhanced anisotropic mechanical properties which can be tailored to potentially any type of tissue.


Subject(s)
Nanocomposites , Tissue Adhesives , Adhesives/chemistry , Biocompatible Materials/pharmacology , Hydrogels/chemistry , Nanocomposites/chemistry , Sutures , Tissue Adhesives/chemistry
5.
Macromol Biosci ; : e2300376, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38031512

ABSTRACT

Even with the current advancements in wound management, addressing most skin injuries and wounds continues to pose a significant obstacle for the healthcare industry. As a result, researchers are now focusing on creating innovative materials utilizing cellulose and its derivatives. Cellulose, the most abundant biopolymer in nature, has unique properties that make it a promising material for wound healing, such as biocompatibility, tunable physiochemical characteristics, accessibility, and low cost. 3D bioprinting technology has enabled the production of cellulose-based wound dressings with complex structures that mimic the extracellular matrix. The inclusion of bioactive molecules such as growth factors offers the ability to aid in promoting wound healing, while cellulose creates an ideal environment for controlled release of these biomolecules and moisture retention. The use of 3D bioprinted cellulose-based wound dressings has potential benefits for managing chronic wounds, burns, and painful wounds by promoting wound healing and reducing the risk of infection. This review provides an up-to-date summary of cellulose-based dressings manufactured by 3D bioprinting techniques by looking into wound healing biology, biofabrication methods, cellulose derivatives, and the existing cellulose bioinks targeted toward wound healing.

6.
Adv Healthc Mater ; 12(20): e2203172, 2023 08.
Article in English | MEDLINE | ID: mdl-36971091

ABSTRACT

Currently, the demand for more reliable drug screening devices has made scientists and researchers develop novel potential approaches to offer an alternative to animal studies. Organ-on-chips are newly emerged platforms for drug screening and disease metabolism investigation. These microfluidic devices attempt to recapitulate the physiological and biological properties of different organs and tissues using human-derived cells. Recently, the synergistic combination of additive manufacturing and microfluidics has shown a promising impact on improving a wide array of biological models. In this review, different methods are classified using bioprinting to achieve the relevant biomimetic models in organ-on-chips, boosting the efficiency of these devices to produce more reliable data for drug investigations. In addition to the tissue models, the influence of additive manufacturing on microfluidic chip fabrication is discussed, and their biomedical applications are reviewed.


Subject(s)
Bioprinting , Animals , Humans , Bioprinting/methods , Drug Evaluation, Preclinical/methods , Microfluidics/methods , Lab-On-A-Chip Devices , Biomimetics
7.
ACS Appl Mater Interfaces ; 15(12): 16034-16045, 2023 Mar 29.
Article in English | MEDLINE | ID: mdl-36930887

ABSTRACT

Hydrogels with different functionalities such as printability, antifreezing properties, adhesion, biocompatibility, and toughness are being continually developed. However, it has been extremely challenging to design adhesive, antifreezing, tough, and biocompatible multifunctional hydrogels with complex shapes simultaneously and prepare them in a short period. In this paper, novel composite hydrogels, which consist of poly(vinyl alcohol) grafted with styrylpyridinium group (PVA-SbQ) and TEMPO-oxidized cellulose nanofibrils (CNF), were successfully synthesized via UV photo-cross-linking. In addition to UV photo-cross-linking, the PVA-SbQ/CNF hydrogels with different shapes could be rapidly printed by facile visible light-based stereolithography printing and laser direct-writing without any photoinitiators in 3 min and 30 s, respectively. The results show that PVA-SbQ/CNF hydrogels are biocompatible because there are no photoinitiators and cross-linkers required during the printing process under visible light. Moreover, the adhesive, antifreezing, mechanical properties, and water-binding capacity of PVA-SbQ/CNF with high-water contents improved significantly as the CNF contents increased. Such hydrogels, which combine multiple advantages, present great potential for application in wound dressings and portable devices with specific requirements for shapes, adhesion, toughness, and tolerance in extreme environments such as dry environments and low temperatures.


Subject(s)
Adhesives , Hydrogels , Hydrogels/chemistry , Water/chemistry , Light , Cold Temperature
8.
Biomater Adv ; 147: 213318, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36746100

ABSTRACT

Currently, the lack of bioinks and long printing time limits the further development of biofabrication. Here we report a novel biocompatible, multi-functional and tough 3D printable hydrogel via visible light photocrosslinking of polyvinyl alcohol bearing styrylpyridinium group (PVA-SbQ). The high-resolution PVA-SbQ hydrogels with different designed shapes can be generated via laser direct-writing in 30 s without extra toxic crosslinkers or photoinitiators, and demonstrates excellent biocompatibility. The rapid laser direct-writing technology also results in a super-strong, tough hydrogel with excellent adhesive, swelling, self-healing, and photo-tunable properties due to the photodimerization of styrylpyridinium (SbQ) groups and the left-over massive amount of free hydroxyl groups in the hydrogel. For example, the maximum tensile strength, elongation, compressive strength adhesive strength of printed PVA-SbQ hydrogels can reach 1.0 MPa, 810 %, 33 MPa, 31 kPa, and 25,000 % respectively. And these properties can be adjusted by controlling the parameters for laser direct-writing. In addition, the introduced nitrogen cations by SbQ groups further endow hydrogels with the potential to develop novel functionality, which is demonstrated by integrating negatively charged nanocelluloses in the PVA-SbQ system to develop underwater adhesives, anti-freezing (-24.9 °C), and anti-bacterial hydrogels. This discovery opens multiple doors for developing PVA-SbQ based multi-functional hydrogel for various applications including biofabrication and tissue engineering.


Subject(s)
Biocompatible Materials , Hydrogels , Tensile Strength , Light , Writing , Adhesives
9.
Biofabrication ; 15(2)2023 02 14.
Article in English | MEDLINE | ID: mdl-36716495

ABSTRACT

Vascularization is an indispensable requirement for fabricating large solid tissues and organs. The natural vasculature derived from medical imaging modalities for large tissues and organs are highly complex and convoluted. However, the present bioprinting capabilities limit the fabrication of such complex natural vascular networks. Simplified bioprinted vascular networks, on the other hand, lack the capability to sustain large solid tissues. This work proposes a generalized and adaptable numerical model to design the vasculature by utilizing the tissue/organ anatomy. Starting with processing the patient's medical images, organ structure, tissue-specific cues, and key vasculature tethers are determined. An open-source abdomen magnetic resonance image dataset was used in this work. The extracted properties and cues are then used in a mathematical model for guiding the vascular network formation comprising arterial and venous networks. Next, the generated three-dimensional networks are used to simulate the nutrient transport and consumption within the organ over time and the regions deprived of the nutrients are identified. These regions provide cues to evolve and optimize the vasculature in an iterative manner to ensure the availability of the nutrient transport throughout the bioprinted scaffolds. The mass transport of six components of cell culture media-glucose, glycine, glutamine, riboflavin, human serum albumin, and oxygen was studied within the organ with designed vasculature. As the vascular structure underwent iterations, the organ regions deprived of these key components decreased significantly highlighting the increase in structural complexity and efficacy of the designed vasculature. The numerical method presented in this work offers a valuable tool for designing vascular scaffolds to guide the cell growth and maturation of the bioprinted tissues for faster regeneration post bioprinting.


Subject(s)
Bioprinting , Tissue Scaffolds , Humans , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Bioprinting/methods , Printing, Three-Dimensional
10.
Gels ; 8(10)2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36286183

ABSTRACT

The development of adhesive hydrogel materials has brought numerous advances to biomedical engineering. Hydrogel adhesion has drawn much attention in research and applications. In this paper, the study of hydrogel adhesion is no longer limited to the surface of hydrogels. Here, the effect of the internal crosslinking degree of hydrogels prepared by different methods on hydrogel adhesion was explored to find the generality. The results show that with the increase in crosslinking degree, the hydrogel adhesion decreased significantly due to the limitation of segment mobility. Moreover, two simple strategies to improve hydrogel adhesion generated by hydrogen bonding were proposed. One was to keep the functional groups used for hydrogel adhesion and the other was to enhance the flexibility of polymer chains that make up hydrogels. We hope this study can provide another approach for improving the hydrogel adhesion generated by hydrogen bonding.

11.
Micromachines (Basel) ; 13(3)2022 Feb 25.
Article in English | MEDLINE | ID: mdl-35334656

ABSTRACT

The need for organ transplants has risen, but the number of available organ donations for transplants has stagnated worldwide. Regenerative medicine has been developed to make natural organs or tissue-like structures with biocompatible materials and solve the donor shortage problem. Using biomaterials and embedded cells, a bioprinter enables the fabrication of complex and functional three-dimensional (3D) structures of the organs or tissues for regenerative medicine. Moreover, conventional surgical 3D models are made of rigid plastic or rubbers, preventing surgeons from interacting with real organ or tissue-like models. Thus, finding suitable biomaterials and printing methods will accelerate the printing of sophisticated organ structures and the development of realistic models to refine surgical techniques and tools before the surgery. In addition, printing parameters (e.g., printing speed, dispensing pressure, and nozzle diameter) considered in the bioprinting process should be optimized. Therefore, machine learning (ML) technology can be a powerful tool to optimize the numerous bioprinting parameters. Overall, this review paper is focused on various ideas on the ML applications of 3D printing and bioprinting to optimize parameters and procedures.

12.
J Biomed Mater Res A ; 110(3): 708-724, 2022 03.
Article in English | MEDLINE | ID: mdl-34558808

ABSTRACT

Gelatin methacryloyl (GelMA), a photocrosslinkable gelatin-based hydrogel, has been immensely used for diverse applications in tissue engineering and drug delivery. Apart from its excellent functionality and versatile mechanical properties, it is also suitable for a wide range of fabrication methodologies to generate tissue constructs of desired shapes and sizes. Despite its exceptional characteristics, it is predominantly limited by its weak mechanical strength, as some tissue types naturally possess high mechanical stiffness. The use of high GelMA concentrations yields high mechanical strength, but not without the compromise in its porosity, degradability, and three-dimensional (3D) cell attachment. Recently, GelMA has been blended with various natural and synthetic biomaterials to reinforce its physical properties to match with the tissue to be engineered. Among these, nanomaterials have been extensively used to form a composite with GelMA, as they increase its biological and physicochemical properties without affecting the unique characteristics of GelMA and also introduce electrical and magnetic properties. This review article presents the recent advances in the formation of hybrid GelMA nanocomposites using a variety of nanomaterials (carbon, metal, polymer, and mineral-based). We give an overview of each nanomaterial's characteristics followed by a discussion of the enhancement in GelMA's physical properties after its incorporation. Finally, we also highlight the use of each GelMA nanocomposite for different applications, such as cardiac, bone, and neural regeneration.


Subject(s)
Gelatin , Tissue Engineering , Gelatin/chemistry , Hydrogels/chemistry , Methacrylates , Nanogels , Tissue Engineering/methods , Tissue Scaffolds/chemistry
13.
Biomed Eng Lett ; 11(4): 335-365, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34513114

ABSTRACT

Humans have suffered from a variety of infectious diseases since a long time ago, and now a new infectious disease called COVID-19 is prevalent worldwide. The ongoing COVID-19 pandemic has led to research of the effective methods of diagnosing respiratory infectious diseases, which are important to reduce infection rate and help the spread of diseases be controlled. The onset of COVID-19 has led to the further development of existing diagnostic methods such as polymerase chain reaction, reverse transcription polymerase chain reaction, and loop-mediated isothermal amplification. Furthermore, this has contributed to the further development of micro/nanotechnology-based diagnostic methods, which have advantages of high-throughput testing, effectiveness in terms of cost and space, and portability compared to conventional diagnosis methods. Micro/nanotechnology-based diagnostic methods can be largely classified into (1) nanomaterials-based, (2) micromaterials-based, and (3) micro/nanodevice-based. This review paper describes how micro/nanotechnologies have been exploited to diagnose respiratory infectious diseases in each section. The research and development of micro/nanotechnology-based diagnostics should be further explored and advanced as new infectious diseases continue to emerge. Only a handful of micro/nanotechnology-based diagnostic methods has been commercialized so far and there still are opportunities to explore.

14.
Biofabrication ; 13(4)2021 09 27.
Article in English | MEDLINE | ID: mdl-34507314

ABSTRACT

Hyaluronic acid is a native extra-cellular matrix derivative that promises unique properties, such as anti-inflammatory response and cell-signaling with tissue-specific applications under its bioactive properties. Here, we investigate the importance of the duration of synthesis to obtain photocrosslinkable methacrylated hyaluronic acid (MeHA) with high degree of substitution. MeHA with high degree of substitution can result in rapid photocrosslinking and can be used as a bioink for stereolithographic (SLA) three dimensional 3D bioprinting. Increased degree of substitution results Our findings show that a ten-day synthesis results in an 88% degree of methacrylation (DM), whereas three-day and five-day syntheses result in 32% and 42% DM, respectively. The rheological characterization revealed an increased rate of photopolymerization with increasing DM. Further, we developed a hybrid bioink to overcome the non-cell-adhesive nature of MeHA by combining it with gelatin methacryloyl (GelMA) to fabricate 3D cell-laden hydrogel scaffolds. The hybrid bioink exhibited a 55% enhancement in stiffness compared to MeHA only and enabled cell-adhesion while maintaining high cell viability. Investigations also revealed that the hybrid bioink was a more suitable candidate for stereolithography (SLA) 3D bioprinting than MeHA because of its mechanical strength, printability, and cell-adhesive nature. This research lays out a firm foundation for the development of a stable hybrid bioink with MeHA and GelMA for first-ever use with SLA 3D bioprinting.


Subject(s)
Bioprinting , Gelatin , Hyaluronic Acid , Hydrogels , Printing, Three-Dimensional , Stereolithography , Tissue Engineering , Tissue Scaffolds
15.
Sci Rep ; 11(1): 13378, 2021 06 28.
Article in English | MEDLINE | ID: mdl-34183720

ABSTRACT

The highly infectious nature of SARS-CoV-2 necessitates the use of widespread testing to control the spread of the virus. Presently, the standard molecular testing method (reverse transcriptase-polymerase chain reaction, RT-PCR) is restricted to the laboratory, time-consuming, and costly. This increases the turnaround time for getting test results. This study sought to develop a rapid, near-patient saliva-based test for COVID-19 (Saliva-Dry LAMP) with similar accuracy to that of standard RT-PCR tests. A lyophilized dual-target reverse transcription-loop-mediated isothermal amplification (RT-LAMP) test with fluorometric detection by the naked eye was developed. The assay relies on dry reagents that are room temperature stable. A device containing a centrifuge, heat block, and blue LED light system was manufactured to reduce the cost of performing the assay. This test has a limit of detection of 1 copy/µL and achieved a positive percent agreement of 100% [95% CI 88.43% to 100.0%] and a negative percent agreement of 96.7% [95% CI 82.78-99.92%] relative to a reference standard test. Saliva-Dry LAMP can be completed in 105 min. Precision, cross-reactivity, and interfering substances analysis met international regulatory standards. The combination of ease of sample collection, dry reagents, visual detection, low capital equipment cost, and excellent analytical sensitivity make Saliva-Dry LAMP particularly useful for resource-limited settings.


Subject(s)
COVID-19/diagnosis , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , RNA, Viral/analysis , Saliva/virology , COVID-19/virology , Fluorometry , Humans , Limit of Detection , Molecular Diagnostic Techniques/instrumentation , Molecular Diagnostic Techniques/standards , Nucleic Acid Amplification Techniques/instrumentation , Nucleic Acid Amplification Techniques/standards , RNA, Viral/standards , Reference Standards , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Temperature
16.
RSC Adv ; 11(39): 23881-23891, 2021 Jul 06.
Article in English | MEDLINE | ID: mdl-35479023

ABSTRACT

Supplies of respiratory masks have recently become a concern due to the onset of the SARS-CoV-2 pandemic. Sanitization and reuse of masks can alleviate high mask consumption and production stresses. In the present work, improved sanitization potency of vaporous hydrogen peroxide (VHP) treatment of resilient bacterial spores while retaining polymeric filter performance was explored. A batch fumigation chamber with hydrogen peroxide (H2O2) vapor and ozone (O3) is featured, followed by intense pulsed light (IPL) flash treatments. A resilient bacterial indicator, Geobacillus stearothermophilus (G. stearothermophilus), was utilized to compare the efficacy of various H2O2 concentrations in combination with O3 and IPL. It was found that exposure to 30 minutes of 4.01 L min-1 0.03% H2O2 aqueous vapor and 3 g h-1 O3 followed by 10 IPL flashes per side completely inactivated G. stearothermophilus. The xenon sourced IPL irradiation was found to synergistically enhance radical production and strengthen the complementary biocidal interaction of H2O2 with O3. Due to the synergistic effects, H2O2 was able to sanitize at a diluted concentration of 0.03% H2O2. The physical properties, such as surface potential, tensile strength, hydrophobicity, and filtration efficiency of >300 nm saline water aerosol of fibrous polypropylene (PP) sheets, were maintained. In addition, no residue of sanitizers was detected, thus confirming the biosafety and applicability of this method to disposable masks. Performance was benchmarked and compared with commercially available processes. The synergistic regime was found to achieve sterilization of G. stearothermophilus at drastically reduced H2O2 concentrations and in ambient conditions relative to commercial methods.

17.
J Biomed Mater Res B Appl Biomater ; 109(5): 622-629, 2021 05.
Article in English | MEDLINE | ID: mdl-32945089

ABSTRACT

Polyether ether ketone (PEEK) has shown great promise for implant and biomedical applications because of its excellent chemical, mechanical, and biocompatible properties. However, PEEK is bioinert, which causes weak cell adhesion and limits its use for biomedical applications such as bone implants. Therefore, the activation of the PEEK's surface for cell attachment is desirable. In this study, oxygen plasma and gelatin were used to modify PEEK's surface and the effects of surface roughness, wettability, and cell adhesion to the surface were studied. Surface roughness was measured using a laser scanning confocal microscope, and wettability was measured using the sessile drop method. There was no significant difference in the roughness of the three samples. The gelatin-coated surface showed higher wettability than the plasma-modified or control samples. The cell attachment and proliferation rate were assessed by scanning electron microscopy and the XTT assay, respectively. The XTT assay results indicated that a greater number of cells grew on the gelatin-coated PEEK surface than on the control or plasma-treated surfaces. These results confirmed that the plasma and gelatin treatments enhanced the biocompatibility of the PEEK samples. The increase in biocompatibility could make PEEK a better material candidate for treating bone related injuries and defects.


Subject(s)
Benzophenones/chemistry , Ketones/chemistry , Polymers/chemistry , Animals , Biocompatible Materials/chemistry , Cell Adhesion/drug effects , Cell Proliferation , Gelatin/pharmacology , Mice , Microscopy, Confocal , Microscopy, Electron, Scanning , NIH 3T3 Cells , Osteoblasts/cytology , Osteogenesis/drug effects , Oxygen/chemistry , Polyethylene Glycols/chemistry , Prostheses and Implants , Surface Properties , Titanium/chemistry , Wettability
18.
Macromol Biosci ; 21(1): e2000317, 2021 01.
Article in English | MEDLINE | ID: mdl-33043610

ABSTRACT

Bioinks play a key role in determining the capability of the biofabricatoin processes and the resolution of the printed constructs. Excellent biocompatibility, tunable physical properties, and ease of chemical or biological modifications of gelatin methacryloyl (GelMA) have made it an attractive choice as bioinks for biomanufacturing of various tissues or organs. However, the current preparation methods for GelMA-based bioinks lack the ability to tailor their physical properties for desired bioprinting methods. Inherently, GelMA prepolymer solution exhibits a fast sol-gel transition at room temperature, which is a hurdle for its use in stereolithography (SLA) bioprinting. Here, synthesis parameters are optimized such as solvents, pH, and reaction time to develop GelMA bioinks which have a slow sol-gel transition at room temperature and visible light crosslinkable functions. A total of eight GelMA combinations are identified as suitable for digital light processing (DLP)-based SLA (DLP-SLA) bioprinting through systematic characterizations of their physical and rheological properties. Out of various types of GelMA, those synthesized in reverse osmosis (RO) purified water (referred to as RO-GelMA) are regarded as most suitable to achieve high DLP-SLA printing resolution. RO-GelMA-based bioinks are also found to be biocompatible showing high survival rates of encapsulated cells in the photocrosslinked gels. Additionally, the astrocytes and fibroblasts are observed to grow and integrate well within the bioprinted constructs. The bioink's superior physical and photocrosslinking properties offer pathways of tuning the scaffold microenvironment and highlight the applicability of developed GelMA bioinks in various tissue engineering and regenerative medicine applications.


Subject(s)
Bioprinting , Gelatin/pharmacology , Methacrylates/pharmacology , Stereolithography , Tissue Engineering , Cell Survival/drug effects , Gelatin/chemical synthesis , Gelatin/radiation effects , Humans , Hydrogels/chemistry , Hydrogels/pharmacology , Ink , Light , Methacrylates/chemical synthesis , Methacrylates/radiation effects , Printing, Three-Dimensional , Tissue Scaffolds/chemistry
19.
Small ; 16(30): e2000941, 2020 07.
Article in English | MEDLINE | ID: mdl-32588966

ABSTRACT

Cells in vivo are constantly subjected to multiple microenvironmental mechanical stimuli that regulate cell function. Although 2D cell responses to the mechanical stimulation have been established, these methods lack relevance as physiological cell microenvironments are in 3D. Moreover, the existing platforms developed for studying the cell responses to mechanical cues in 3D either offer low-throughput, involve complex fabrication, or do not allow combinatorial analysis of multiple cues. Considering this, a stretchable high-throughput (HT) 3D cell microarray platform is presented that can apply dynamic mechanical strain to cells encapsulated in arrayed 3D microgels. The platform uses inkjet-bioprinting technique for printing cell-laden gelatin methacrylate (GelMA) microgel array on an elastic composite substrate that is periodically stretched. The developed platform is highly biocompatible and transfers the applied strain from the stretched substrate to the cells. The HT analysis is conducted to analyze cell mechano-responses throughout the printed microgel array. Also, the combinatorial analysis of distinct cell behaviors is conducted for different GelMA microenvironmental stiffnesses in addition to the dynamic stretch. Considering its throughput and flexibility, the developed platform can readily be scaled up to introduce a wide range of microenvironmental cues and to screen the cell responses in a HT way.


Subject(s)
Bioprinting , High-Throughput Screening Assays , Gelatin , Hydrogels , Methacrylates , Printing, Three-Dimensional
20.
Ann Biomed Eng ; 48(7): 1955-1970, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32504140

ABSTRACT

3D bioprinting technology is a promising approach for corneal stromal tissue regeneration. In this study, gelatin methacrylate (GelMA) mixed with corneal stromal cells was used as a bioink. The visible light-based stereolithography (SLA) 3D bioprinting method was utilized to print the anatomically similar dome-shaped structure of the human corneal stroma. Two different concentrations of GelMA macromer (7.5 and 12.5%) were tested for corneal stroma bioprinting. Due to high macromer concentrations, 12.5% GelMA was stiffer than 7.5% GelMA, which made it easier to handle. In terms of water content and optical transmittance of the bioprinted scaffolds, we observed that scaffold with 12.5% GelMA concentration was closer to the native corneal stroma tissue. Subsequently, cell proliferation, gene and protein expression of human corneal stromal cells encapsulated in the bioprinted scaffolds were investigated. Cytocompatibility in 12.5% GelMA scaffolds was observed to be 81.86 and 156.11% at day 1 and 7, respectively, which were significantly higher than those in 7.5% GelMA scaffolds. Elongated corneal stromal cells were observed in 12.5% GelMA samples after 7 days, indicating the cell attachment, growth, and integration within the scaffold. The gene expression of collagen type I, lumican and keratan sulfate increased over time for the cells cultured in 12.5% GelMA scaffolds as compared to those cultured on the plastic tissue culture plate. The expression of collagen type I and lumican were also visualized using immunohistochemistry after 28 days. These findings imply that the SLA 3D bioprinting method with GelMA hydrogel bioinks is a promising approach for corneal stroma tissue biofabrication.


Subject(s)
Bioprinting , Corneal Stroma/growth & development , Printing, Three-Dimensional , Stereolithography , Tissue Engineering/methods , Collagen Type I , Corneal Stroma/cytology , Gelatin/chemistry , Humans , Hydrogels/chemistry , Lumican , Methacrylates/chemistry , Tissue Scaffolds
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