Biomedical Tissue Research Articles

3D Printability Assessment of Poly(octamethylene maleate (anhydride) citrate) and Poly(ethylene glycol) Diacrylate Copolymers for Biomedical Applications.

Herein, we present the first example of 3D printing with poly(octamethylene maleate (anhydride) citrate) (POMaC), a bio-adhesive material which has shown particular promise for implantable biomedical devices. The current methods to fabricate such devices made from POMaC are hindered by the imposed constraints of designing complex molds. We demonstrate the feasibility of exploiting additive manufacturing to 3D print structural functional materials consisting of POMaC. We present 3D printing of biomaterial copolymers consisting of mixtures of poly(ethylene glycol) diacrylate (PEGDA) and POMaC at different ratios. The required parameters were optimized, and characterization of the printing fidelity and physical properties was performed. We have also demonstrated that a range of mechanical properties can be achieved by tuning the POMaC/PEGDA ratio. The biocompatibility of the copolymers was ascertained via a cell viability assay. Such tunable 3D printed biomaterials consisting of POMaC and PEGDA will have significant potential application in the development of functional biomaterial tissue scaffolds and biomedical devices for the future of personalized medicine.

Biobanking in times of crisis – The COVID-19 Autopsy and Biosample Registry Baden-Wuerttemberg

Biobanking plays a critical role in diagnostics, biomarker research and development of novel treatment approaches for various diseases. In urgent need of understanding, preventing and treating coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the importance of biobanking including data sharing and management further increased. To provide high quality tissue biomaterials and data for research and public health, the COVID-19 Autopsy and Biosample Registry was established in the state of Baden-Wuerttemberg (BW) in Germany, combining expertise and technologies of the Institutes of Pathology of the five university hospitals in BW (Heidelberg, Tübingen, Ulm, Freiburg, Mannheim). The COVID-19 Autopsy and Biosample Registry BW comprises tissue samples from autopsies and associated data of deceased patients in the context of SARS-CoV-2 infection and/or vaccination against SARS-CoV-2. The aim is to collect autopsy biospecimens, associated clinical and diagnostic data in a timely manner, register them, make them accessible for research projects and thus to support especially tissue-related research addressing COVID-19. By now, the BW network holds multiple collaborations and supported numerous publications to increase the understanding of COVID-19 disease. The achievements of the BW network as a landmark biobanking model project represent a potential blueprint for future disease-related biobanking and registry effort.

Mechanically Diverse Gels with Equal Solvent Content.

Mechanically diverse polymer gels are commonly integrated into biomedical devices, soft robots, and tissue engineering scaffolds to perform distinct yet coordinated functions in wet environments. Such multigel systems are prone to volume fluctuations and shape distortions due to differential swelling driven by osmotic solvent redistribution. Living systems evade these issues by varying proximal tissue stiffness at nearly equal water concentration. However, this feature is challenging to replicate with synthetic gels: any alteration of cross-link density affects both the gel’s swellability and mechanical properties. In contrast to the conventional coupling of physical properties, we report a strategy to tune the gel modulus independent of swelling ratio by regulating network strand flexibility with brushlike polymers. Chemically identical gels were constructed with a broad elastic modulus range at a constant solvent fraction by utilizing multidimensional network architectures. The general design-by-architecture framework is universally applicable to both organogels and hydrogels and can be further adapted to different practical applications.

Reduced Collateral Tissue Damage Using Thermal-Feedback-Based Power Adaptation of an Electrosurgery Inverter.

Well-selected power with accurate delivery is of importance in electrosurgery to generate proper temperature at the cutting site, and thus, reduce undesired collateral tissue damages. Conventional electrosurgery generator (ESG) targets tracking a preset power, manually set by surgeons per their experience before the surgery, with high accurate delivery. It is possible that this fixed power setting is not at the optimal point and, thus, increases the possibility of added-collateral biomedical tissue damage. To eliminate the potential negative impact of the fixed and ill-suited power setting, a real-time feedback control scheme is outlined in this article to adjust the preset power of the ESG to create an adaptive power reference, which is then tracked using an experimental high-frequency inverter (HFI) that enables electrosurgery with a fundamental (sinusoidal) output frequency of 390 kHz. Subsequently, experiments using the gallium nitride (GaN)-based HFI are carried out to demonstrate the efficacy of the new variable-power approach over the conventional fixed power approach in terms of collateral tissue damage reduction.

Design of a Mechanobioreactor to Apply Anisotropic, Biaxial Strain to Large Thin Biomaterials for Tissue Engineered Heart Valve Applications.

Repair and replacement solutions for congenitally diseased heart valves capable of post-surgery growth and adaptation have remained elusive. Tissue engineered heart valves (TEHVs) offer a potential biological solution that addresses the drawbacks of existing valve replacements. Typically, TEHVs are made from thin, fibrous biomaterials that either become cell populated in vitro or in situ. Often, TEHV designs poorly mimic the anisotropic mechanical properties of healthy native valves leading to inadequate biomechanical function. Mechanical conditioning of engineered tissues with anisotropic strain application can induce extracellular matrix remodelling to alter the anisotropic mechanical properties of a construct, but implementation has been limited to small-scale set-ups. To address this limitation for TEHV applications, we designed and built a mechanobioreactor capable of modulating biaxial strain anisotropy applied to large, thin, biomaterial sheets in vitro. The bioreactor can independently control two orthogonal stretch axes to modulate applied strain anisotropy on biomaterial sheets from 13×13mm2 to 70×40 mm2. A design of experiments was performed using experimentally validated finite element (FE) models and demonstrated that biaxial strain was applied uniformly over a larger percentage of the cell seeded area for larger sheets (13×13 mm2: 58% of sheet area vs. 52×31 mm2: 86% of sheet area). Furthermore, bioreactor prototypes demonstrated that over 70% of the cell seeding area remained uniformly strained under different prescribed protocols: equibiaxial amplitudes between 5 to 40%, cyclic frequencies between 0.1 to 2.5 Hz and anisotropic strain ratios between 0:1 (constrained uniaxial) to 2:1. Lastly, proof-of-concept experiments were conducted where we applied equibiaxial (εx = εy = 8.75%) and anisotropic (εx = 12.5%, εy = 5%) strain protocols to cell-seeded, electrospun scaffolds. Cell nuclei and F-actin aligned to the vector-sum strain direction of each prescribed protocol (nuclei alignment: equibiaxial: 43.2°±1.8°, anisotropic: 17.5°±1.7°; p<0.001). The abilities of this bioreactor to prescribe different strain amplitude, frequency and strain anisotropy protocols to cell-seeded scaffolds will enable future studies into the effects of anisotropic loading protocols on mechanically conditioned TEHVs and other engineered planar connective tissues.

Poly(3,4‐ethylenedioxythiophene):Poly(styrene sulfonate) in antibacterial, tissue engineering and biosensors applications: Progress, challenges and perspectives

AbstractWith the advancement of applications in biomedicines and bioelectronics, conducting polymers have attained huge significant attention. For such applications, poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is considered a potential conducting polymer because of its low cost, considerable stability, high conductivity and mechanical strength. Most importantly, its easy aqueous solution processability makes it more attractive. Over the last few years, PEDOT:PSS has been predominantly explored and investigated for different optoelectronic flexible devices, and recently it has been studied for biomedical applications. PEDOT:PSS based materials have made progress in biomedicines due to their properties such as biocompatibility, cell proliferation, antibacterial, nontoxicity and so forth. To adjust the desirable properties, special attention is required for altering the structure of PEDOT:PSS material. PEDOT:PSS offers excellent antibacterial properties against both gram‐positive and gram‐negative bacteria. Moreover, PEDOT:PSS demonstrates an important role in sensing human body humidity, pressure control, glucose detection, as well as employed in human sweat sensors. Besides these, PEDOT:PSS has been studied as a scaffold for endothelial cell preservation. There are several issues which need to be resolved in the future, such as improved biocompatibility and stability to explore the PEDOT:PSS based composite materials in biomedical applications. However, a related review article is lacking, directed on the PEDOT:PSS biomedical applications, namely, antibacterial, tissue engineering, and biosensing. Therefore, the current article summarizes importance of PEDOT:PSS for biomedical applications, and main emphasis is given to its recent advances, challenges and perspectives.

Perspective on non-invasive and non-destructive photoacoustic and photothermal applications

This contribution intends to convince readers that by virtue of the rich physics involved, optical excitation, thermal diffusion, thermal expansion, and acoustic wave propagation, and of the optical nature of the involved excitation and detection, photoacoustic and photothermal methods offer a unique combination of features that makes them very attractive for exploitation in a wide area of scientific and technological fields that involve material property evaluation. A perspective is also given on the high potential of these methods for substantial advances beyond the state of the art in a diverse selection of scientific disciplines: biomedical diagnostics, cell and tissue mechanobiology, thin film and interface characterization, characterization of the microstructure of solids, and the physics of relaxation in glass-forming liquids.

Hierarchical Structures in Macromolecule-Assembled Synthetic Cells.

Various models of synthetic cells have been developed as researchers have sought to explore the origins of life. Based on the fact that structural complexity is the foundation of higher-order functions, this review focuses on hierarchical structures in synthetic cell models that are inspired by living systems, in which macromolecules are the dominant participants. The underlying advantages and functions provided by biomimetic higher-order structures are discussed from four perspectives, including hierarchical structures in membranes, in the composite construction of membrane-coated artificial cytoplasm, in organelle-like subcellular compartments, as well as in synthetic cell-cell assembled synthetic tissues. In parallel, various feasible driving forces and approaches for the fabrication of such higher-order structures are showcased. Furthermore, both the implemented and potential applications of biomimetic systems, bottom-up biosynthesis, biomedical tissue engineering, and disease therapy are highlighted. This thriving field is gradually narrowing the gap between fundamental research and applied science.

Detailed Investigation of Three-Dimensional Modeling and Printing Technologies from Medical Images to Analyze Femoral Head Fractures Using Finite Element Analysis

Objectives: One of the fields, where additive manufacturing has numerous applications, is biomedical engineering. 3D printing is preferred over traditional manufacturing methodologies, mostly while developing subject-specific implants and medical devices. This study aims to provide a process flow detailing all the stages starting from the acquisition of radiological images from different imaging modalities; such as computed tomography (CT) and magnetic resonance imaging (MRI) to the printing of the bone morphology and finite element analysis; including the validation process.Materials & Methods: First, the CT scan of a lower abdomen area of a patient was converted into a 3D image using interactive medical imaging control system software. The segmentation process was applied to isolate the femoral head from the soft tissue and the pelvic bone. After the roughness errors and the gaps in the segments were removed using the 3Matic software, the file was converted to stereolithography (STL) file format to transfer to the 3D printer. The printing process was carried out via commercial powder-based Selective Laser Sintering (SLS) printer. The subject-specific femoral head model was formed in 3D. The Finite Element Analysis (FEA) of the femoral head was performed using a commercial FE software package.Results: The results show that experimental analysis and the CT scan-based FEA were compatible both for the stress distributions and the strain values as predicted by the models (R2=0.99). The deviation was calculated as approximately 12% between the experimental results and the Finite Element (FE) results. In addition, it was observed that the SLS technique produced useful results for modeling biomedical tissues with about 24x faster prototyping time.Conclusion: The prescribed process flow could be utilized in clinical settings for the pre-planning of the surgeries (≈428 minutes for femoral head) and also as an educational tool in the biomedical engineering field.

The Role of Interstitial Fluid Pressure in Cerebral Porous Biomaterial Integration.

Recent advances in biomaterials offer new possibilities for brain tissue reconstruction. Biocompatibility, provision of cell adhesion motives and mechanical properties are among the present main design criteria. We here propose a radically new and potentially major element determining biointegration of porous biomaterials: the favorable effect of interstitial fluid pressure (IFP). The force applied by the lymphatic system through the interstitial fluid pressure on biomaterial integration has mostly been neglected so far. We hypothesize it has the potential to force 3D biointegration of porous biomaterials. In this study, we develop a capillary hydrostatic device to apply controlled in vitro interstitial fluid pressure and study its effect during 3D tissue culture. We find that the IFP is a key player in porous biomaterial tissue integration, at physiological IFP levels, surpassing the known effect of cell adhesion motives. Spontaneous electrical activity indicates that the culture conditions are not harmful for the cells. Our work identifies interstitial fluid pressure at physiological negative values as a potential main driver for tissue integration into porous biomaterials. We anticipate that controlling the IFP level could narrow the gap between in vivo and in vitro and therefore decrease the need for animal screening in biomaterial design.

Progress in the Development of Graphene-Based Biomaterials for Tissue Engineering and Regeneration.

Over the last few decades, tissue engineering has become an important technology for repairing and rebuilding damaged tissues and organs. The scaffold plays an important role and has become a hot pot in the field of tissue engineering. It has sufficient mechanical and biochemical properties and simulates the structure and function of natural tissue to promote the growth of cells inward. Therefore, graphene-based nanomaterials (GBNs), such as graphene and graphene oxide (GO), have attracted wide attention in the field of biomedical tissue engineering because of their unique structure, large specific surface area, good photo-thermal effect, pH response and broad-spectrum antibacterial properties. In this review, the structure and properties of typical GBNs are summarized, the progress made in the development of GBNs in soft tissue engineering (including skin, muscle, nerve and blood vessel) are highlighted, the challenges and prospects of the application of GBNs in soft tissue engineering have prospected.

Impacting different structures of injectable pluronic-conjugated alginate (chitosan) hydrogels on their physicochemical characteristics and morphological fibroblast behavior

Chitosan and alginate have inherent properties that have a tremendous impact on the design of in situ thermal sensitive hydrogels due to their ability to fill complex three-dimensional damaged tissue gaps, which can be applied in the tissue regeneration or drug delivery systems. In this study, pluronic F127-conjugated alginate (Alg-F127) and pluronic F127-conjugated chitosan (CS-F127) copolymers were investigated for their physicochemical characteristics and morphological fibroblast behavior. The structures of the amphiphilic copolymers were characterized by 1H-NMR. The aqueous copolymer solution could reversibly change its state from sol to gel via hydrophobic interactions at body temperature (35°–37 °C). At the same concentration of two grafted copolymers, the alginate-based hydrogel performed higher resistance to degrade in both PBS buffer and DMEM. Regarding their specific charge, CS-F127 showed higher protein absorption as compared to the Alg-F127 copolymer. The typical characteristic could induce the different morphological cell behaviors on the hydrogel platforms. Interestingly, as an inherent characteristic of fibroblasts, the cells were elongated and migrated directionally on the Alg-F127 scaffold, though both had excellent cytocompatibility. The improved understanding of the influence of polysaccharide structure on cell behavior has a significant impact on the design of biomedical devices and specific tissue regeneration.

Fully Synthetic 3D Fibrous Scaffolds for Stromal Tissues—Replacement of Animal‐Derived Scaffold Materials Demonstrated by Multilayered Skin (Adv. Mater. 10/2022)

Porous Fibrous Scaffolds The dimensions of electrospun fibers are predestined for synthetic replacement of extracellular matrix structures. In article number 2106780, Tobias Weigel and co-workers generate highly porous electrospun scaffolds, featuring an ensemble of loose fibers and pores of appropriate size to enable applications in engineering animal-free 3D biomedical tissues. The mechanical properties and structural composition describe a tradeoff between current synthetic porous scaffolds and animal-derived hydrogels, which are deployed as electrospun-based multilayered skin equivalents.

State of the art of bone biomaterials and their interactions with stem cells: Current state and future directions.

There has been a rapid increase in bone tissue regeneration since the concept of "tissue engineering." Stem cell-based biomaterials have revolutionized the field of tissue regeneration. Biomaterials play an essential part in bone regeneration through their crucial substratum for cell differentiation, cohesion, and proliferation by manipulating cells. Numerous studies have been carried out in order to create a biomaterial with diverse biological and physical characteristics. Furthermore, they developed a cell microenvironment with the desired pore magnitude to stimulate stem cells to transform them from artificial to biological microenvironments. The current review aims to give a comprehensive overview of stem cells and biomaterials in bone tissue regeneration. Initially, bone biology and its interaction with stem cells and biomaterials are briefly explained. Following that, the behavior and mechanism of biomaterials influencing the stem cells during bone tissue regeneration are emphasized. Lastly, the future outlook for tackling the current challenges for designing biomaterials/stem cell materials for bone tissue engineering (TE) is discussed. Compatible biomaterial for bone regeneration requires evaluating the structure, matrix, composition, flexibility, and nature of native bone tissue defects. The concept of TE offers a platform for designing biologically, physically, and chemically biocompatible biomaterials for stem cells to proliferate and differentiate. Currently, stem cells are increasingly used for TE with a promising outcome due to their self-renewal and differentiation potential. Furthermore, they can secrete biological-active compounds and modulate the fate and behavior of other cells in native tissues. Bone TE may flourish more rapidly and efficiently using stem cells.

A voyage from 3D to 4D printing in nanomedicine and healthcare: part II.

Recent advancements in biomedical tissue engineering are gaining wide interest. Implementing biology of living cells and organisms using technological solutions such as incorporating4D printing and bioprinting for tissue regeneration/tissue repair, organ regeneration, early diagnosis of deadly diseases (particularlycancer, cardiac disordersand tuberculosis) has successfully opened a new generation of biomedical research. The present review primarily addresses the clinical application of 4D printing and bioprinting techniques for applications such as early detection of diseases and drug delivery. Notably, this review continues the discussion from part I regarding published informative data, in vitro and in vivo findings, commercial biosensors for early diseasediagnosis, drug deliveryand current challenges in 4D printing/bioprinting.

Chitosan-collagen-hydroxyapatite membranes for tissue engineering

Tissue engineering is growing in developing new technologies focused on providing effective solutions to degenerative pathologies that affect different types of connective tissues. The search for biocompatible, bioactive, biodegradable, and multifunctional materials has grown significantly in recent years. Chitosan, calcium phosphates collagen, and their combination as composite materials fulfill the required properties and could result in biostimulation for tissue regeneration. In the present work, the chitosan/collagen/hydroxyapatite membranes were prepared with different concentrations of collagen and hydroxyapatite. Cell adhesion was evaluated by MTS assay for two in vitro models. Additionally, cytotoxicity of the different membranes employing hemolysis of erythrocytes isolated from human blood was carried out. The structure of the membranes was analyzed by X-rays diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermal stability properties by thermogravimetric methods (TGA). The highest cell adhesion after 48 h was obtained for chitosan membranes with the highest hydroxyapatite and collagen content. All composite membranes showed good cell adhesion and low cytotoxicity, suggesting that these materials have a significant potential to be used as biomaterials for tissue engineering.Graphical abstract

Preparation and antimicrobial activity of CS/PVA membranes containing silver nitrate

Chitosan/polyvinyl alcohol (CS/PVA) membranes containing silver nitrate have been prepared and investigated for antimicrobial properties of prepared membranes. CS/PVA membranes containing silver nitrate have been successfully prepared by solution casting method. The prepared membranes have been characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction analysis (XRD) methods. The elemental composition of the membranes is studied by energy dispersive analysis of SEM-EDX. Correspondingly, the EDX analysis confirms the presence of silver ions in the chitosan matrix. The antimicrobial activities of the membranes have been tested with wide spectrum of bacteria. Efficiency of the antimicrobial effect against the selected twelve bacteria type and two yeasts is measured by disc diffusion method. Effect of the concentration of silver solutions to the developed CS/PVA membranes was investigated. It is noticed that the antimicrobial activity of membranes is improved with the increased silver concentration as a bactericidal agent, as expected. Our observations suggest that Chitosan/polyvinyl alcohol/Ag (CS/PVA/Ag) membranes have an excellent antimicrobial effect. Thus, developed membranes can easily be applied in various fields such as biomedical sector, tissue engineering and water treatment sector.

Computer Simulation of Magnetoelectric Antenna and Performance Comparison With Micro-Loop

Electromagnetic radiation can be produced using functional materials such as magnetoelectric (ME) composites, in which the magnetoelasticity and piezoelasticity of material are involved. The mechanical nature of the vibrations is used to miniaturize the ME antenna to micro-scale size. The antenna performance evaluation requires a multiphysics analysis of the structure. An ME antenna design and simulation is detailed using the finite element method (FEM) in COMSOL Multiphysics&#x00AE; in which the structural mechanics, electrostatics, and magnetic field physics are coupled together to address the simulation needs. An antenna size of 250 &#x03BC;m &#x00D7; 50 &#x03BC;m &#x00D7; 1 &#x03BC;m is simulated within a static magnetic bias field of 20 mT. The nonlinear isotropic model is used for magnetostrictive material definition in which the prestress is defined by the magnetic bias. The model is linearized for radio frequency (RF) simulations to account for the AC simulation. The antenna farfield radiation pattern and the gain are computed using finite difference time domain (FDTD) by incorporating the extracted nearfield of the ME antenna in COMSOL. The simulated antenna impedance, radiation pattern and antenna gain are compared to an equivalent micro-loop magnetic antenna. In addition, electromagnetic computations are used to evaluate the coupling performance between the ME antenna and a larger loop antenna over a distance up to 20 mm in free space and biomedical tissues to address the potential of using ME antenna in medical implants for wireless communication and wireless power transfer.

An ethical perspective to using bone grafts in dentistry

An ethical perspective to using bone grafts in dentistry

Real-Time Alignment and Reorientation of Polymer Chains in Liquid Crystal Elastomers

Liquid crystal elastomers (LCEs) exhibit soft elasticity due to the alignment and reorientation of mesogens upon mechanical loading, which provides additional mechanisms to absorb and dissipate energy. This enhanced response makes LCEs potentially transformative materials for biomedical devices, tissue replacements, and protective equipment. However, there is a critical knowledge gap in understanding the highly rate-dependent dissipative behaviors of LCEs due to the lack of real-time characterization techniques that probe the microscale network structure and link it to the mechanical deformation of LCEs. In this work, we employ in situ optical measurements to evaluate the alignment and reorientation degree of mesogens in LCEs. The data are correlated to the quantitative physical analysis using polarized Fourier-transform infrared spectroscopy. The time scale of mesogen alignment is determined at different strain levels and loading rates. The mesogen reorientation kinetics is characterized to establish its relationship with the macroscale tensile strain, and compared to theoretical predictions. Overall, this work provides the first detailed study on the time-dependent evolution of mesogen alignment and reorientation in deformed LCEs. It also provides an effective and more accessible approach for other researchers to investigate the structural-property relationships of different types of polymers.