Mechanical Comparison of Headless Screw Fixation and Locking Plate Fixation for Talar Neck Fractures.

For talar neck fractures, open reduction and internal fixation have been thought to facilitate revascularization and prevent osteonecrosis. Newer screw systems allow for placement of cannulated headless screws, which provide compression by virtue of a variable pitch thread. The present study compared the biomechanical fixation strength of cannulated headless variable-pitch screw fixation and locking plate fixation. A reproducible talar neck fracture was created in 14 fresh cadaver talar necks. Talar head fixation was then performed using 2 cannulated headless variable-pitch 4-mm/5-mm diameter (4/5) screws (Acutrak; Acumed, Hillsboro, OR) and locking plate fixation. Headless variable-pitch screw fixation had lower failure displacement than did locking plate fixation. No statistically significant differences were found in failure stiffness, yield stiffness (p = .655), yield load (p = .142), or ultimate load between the 2 fixation techniques. Cannulated headless variable-pitch screw fixation resulted in better failure displacement than locking plate fixation in a cadaveric talus model and could be considered a viable option for talus fracture fixation. Headless, fully threaded, variable-pitch screw fixation has inherent advantages compared with locking plate fixation, because it might cause less damage to the articular surface and can compress the fracture for improved reduction. Additionally, plate fixation can increase the risk of avascular necrosis owing to the wider incision and dissection of soft tissues.

Smart Biomaterials in Biomedical Applications: Current Advances and Possible Future Directions.

Smart biomaterials with the capacity to alter their properties in response to an outside stimulus or from within the environment around them have picked up significant attention in the biomedical community. This is primarily due to the interest in their biomedical applications that may be anticipated from them in a considerable number of dynamic structures and devices. Shape-memory materials are some of these materials that have been exclusively used for these applications. They exhibit unique structural reconfiguration features they adapt as per the provided environmental conditions and can be designed for their enhanced biocompatibility. Numerous research initiatives have focused on these smart biocompatible materials over the last few decades to enhance their biomedical applications. Shape-memory materials play a significant role in this regard to meet new surgical and medical devices' requirements for special features and utility cases. Because of the favorable design variety, different biomedical shape-memory materials can be developed by modifying their chemical and physical behaviors to accommodate the desired requirements. In this review, recent advances and characteristics of smart biomaterials for biomedical applications are described. The authors also discuss about their clinical translations in tissue engineering, drug delivery, and medical devices.

Strength of different Krackow stitch configurations using high-strength suture.

The purpose of the present study concerning high-strength sutures was to determine whether increasing the number of locking loops with different size sutures or decreasing the suture size with increased suture strands would have any influence on the strength of Achilles tendon repair. A total of 32 fresh bovine Achilles tendon specimens were randomly assigned to 4 groups. For 3 of the groups, 1 suture was used (no. 2 or no. 5 FiberWire™ with 2 or 4 Krackow locking loops). For the fourth group, 2 sutures (2-0 FiberWire™) with 2 locking loops were used. After repair, the study groups underwent cyclic loading (0 to 200 N, 200 cycles) and then underwent tension to failure in a testing machine. Cyclic elongation, peak to peak displacement, ultimate load, stiffness, and failure mode were recorded for each specimen. The tendon width and thickness were measured in all specimens. The mean width, thickness, cyclic displacement, load to failure, and pull-out stiffness showed no differences among the 4 groups. The cyclic peak to peak displacements (0.01 ± 0.01 mm) were smallest with the no. 5 suture with 4 locking loops (p < .05), with no failure during cyclic loading, unlike in the other groups. In the group with 2-0 suture with 4 strands and 2 locking loops, 6 failed during cyclic loading. The number of locking loops used might have had an influence on the strength of the Krackow suture configuration using the larger diameter, high-strength sutures. However, decreasing the suture diameter, with a simultaneous increase in the number of strands, failed to improve the initial strength of the repair.

Engineered Liposomes in Interventional Theranostics of Solid Tumors.

Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly "liposome" may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.

Application of Convergent Science and Technology toward Ocular Disease Treatment.

Eyes are one of the main critical organs of the body that provide our brain with the most information about the surrounding environment. Disturbance in the activity of this informational organ, resulting from different ocular diseases, could affect the quality of life, so finding appropriate methods for treating ocular disease has attracted lots of attention. This is especially due to the ineffectiveness of the conventional therapeutic method to deliver drugs into the interior parts of the eye, and the also presence of barriers such as tear film, blood-ocular, and blood-retina barriers. Recently, some novel techniques, such as different types of contact lenses, micro and nanoneedles and in situ gels, have been introduced which can overcome the previously mentioned barriers. These novel techniques could enhance the bioavailability of therapeutic components inside the eyes, deliver them to the posterior side of the eyes, release them in a controlled manner, and reduce the side effects of previous methods (such as eye drops). Accordingly, this review paper aims to summarize some of the evidence on the effectiveness of these new techniques for treating ocular disease, their preclinical and clinical progression, current limitations, and future perspectives.

Biosensor integrated brain-on-a-chip platforms: Progress and prospects in clinical translation.

Because of the brain's complexity, developing effective treatments for neurological disorders is a formidable challenge. Research efforts to this end are advancing as in vitro systems have reached the point that they can imitate critical components of the brain's structure and function. Brain-on-a-chip (BoC) was first used for microfluidics-based systems with small synthetic tissues but has expanded recently to include in vitro simulation of the central nervous system (CNS). Defining the system's qualifying parameters may improve the BoC for the next generation of in vitro platforms. These parameters show how well a given platform solves the problems unique to in vitro CNS modeling (like recreating the brain's microenvironment and including essential parts like the blood-brain barrier (BBB)) and how much more value it offers than traditional cell culture systems. This review provides an overview of the practical concerns of creating and deploying BoC systems and elaborates on how these technologies might be used. Not only how advanced biosensing technologies could be integrated with BoC system but also how novel approaches will automate assays and improve point-of-care (PoC) diagnostics and accurate quantitative analyses are discussed. Key challenges providing opportunities for clinical translation of BoC in neurodegenerative disorders are also addressed.

Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells.

Oxygenating biomaterials can alleviate anoxic stress, stimulate vascularization, and improve engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under a severely oxygen deficient microenvironment. To this end, CPO is microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl (GelMA) hydrogels containing osteogenesis-inducing silicate nanoparticles (SNP hydrogels), OMPs (OMP hydrogels), or both SNP and OMP (SNP/OMP hydrogels) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OMP hydrogels associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk mRNAseq analyses suggest that OMP hydrogels under anoxia regulate osteogenic differentiation pathways more strongly than SNP/OMP or SNP hydrogels under either anoxia or normoxia. Subcutaneous implantations reveal a stronger host cell invasion in SNP hydrogels, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveals progressive differentiation of hMSCs in OMP, SNP, and SNP/OMP hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.

3D Bioprinted Hydrogel Microfluidic Devices for Parallel Drug Screening.

Conventional high-throughput screening (HTS) platforms suffer from the need for large cell volumes, high reagent consumption, significant assembly cost, and handling efforts. The assembly of three-dimensional (3D) bioprinted hydrogel-based microfluidic chips within platforms can address these problems. We present a continuous and seamless manufacturing approach to create a bioprinted microfluidic chips with a circular pattern scalable toward HTS platforms. Digital light processing 3D bioprinting is used to tune the local permeability of our chip, made of polyethylene glycol diacrylate and cell-laden gelatin methacryloyl, for creating predefined gradients of biochemical properties. We measured the flow-induced physical characteristics, the mass transport of drug agents, and the biological features of the proposed chip. We measured reactive oxygen species from the encapsulated cells through an integrated process and showed the capacity of the hydrogel-based chip for creating drug/agent gradients. This work introduces a chip design based on a hydrogel that can be changed and could be used for modern HTS platforms such as in vitro organoids.

Selection of natural biomaterials for micro-tissue and organ-on-chip models.

The desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new technologies to meet clinical expectations and improve patient outcomes fusing disease modeling.

Loofah-chitosan and poly (-3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) based hydrogel scaffolds for meniscus tissue engineering applications.

The meniscus is a fibrocartilaginous tissue that is very important for the stability of the knee joint. However, it has a low ability to heal itself, so damage to it will always lead to articular cartilage degeneration. The goal of this study was to make a new type of meniscus scaffold made of chitosan, loofah mat, and PHBV nanofibers, as well as to describe hydrogel composite scaffolds in terms of their shape, chemical composition, mechanical properties, and temperature. Three different concentrations of genipin (0.1, 0.3, and 0.5 %) were used and the optimal crosslinker concentration was 0.3 % for Chitosan/loofah (CL) and Chitosan/loofah/PHBV fiber (CLF). Scaffolds were seeded using undifferentiated MSCs and incubated for 21 days to investigate the chondrogenic potential of hydrogel scaffolds. Cell proliferation analyses were performed using WST-1 assay, GAG content was analyzed, SEM and fluorescence imaging observed morphologies and cell attachment, and histological and immunohistochemical studies were performed. The in vitro analysis showed no cytotoxic effect and enabled cells to attach, proliferate, and migrate inside the scaffold. In conclusion, the hydrogel composite scaffold is a promising material for engineering meniscus tissue.

Layered double hydroxide-based nanocomposite scaffolds in tissue engineering applications.

Layered double hydroxides (LDHs), when incorporated into biomaterials, provide a tunable composition, controllable particle size, anion exchange capacity, pH-sensitive solubility, high-drug loading efficiency, efficient gene and drug delivery, controlled release and effective intracellular uptake, natural biodegradability in an acidic medium, and negligible toxicity. In this review, we study potential applications of LDH-based nanocomposite scaffolds for tissue engineering. We address how LDHs provide new solutions for nanostructure stability and enhance in vivo studies' success.

Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives.

Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug-body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms.

Tissue Adhesives: From Research to Clinical Translation.

Sutures, staples, clips and skin closure strips are used as the gold standard to close wounds after an injury. In spite of being the present standard of care, the utilization of these conventional methods is precarious amid complicated and sensitive surgeries such as vascular anastomosis, ocular surgeries, nerve repair, or due to the high-risk components included. Tissue adhesives function as an interface to connect the surfaces of wound edges and prevent them from separation. They are fluid or semi-fluid mixtures that can be easily used to seal any wound of any morphology - uniform or irregular. As such, they provide alternatives to new and novel platforms for wound closure methods. In this review, we offer a background on the improvement of distinctive tissue adhesives focusing on the chemistry of some of these products that have been a commercial success from the clinical application perspective. This review is aimed to provide a guide toward innovation of tissue bioadhesive materials and their associated biomedical applications.

Survival and Proliferation under Severely Hypoxic Microenvironments Using Cell-Laden Oxygenating Hydrogels.

Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.

3D Immunocompetent Organ-on-a-Chip Models.

In recent years, engineering of various human tissues in microphysiologically relevant platforms, known as organs-on-chips (OOCs), has been explored to establish in vitro tissue models that recapitulate the microenvironments found in native organs and tissues. However, most of these models have overlooked the important roles of immune cells in maintaining tissue homeostasis under physiological conditions and in modulating the tissue microenvironments during pathophysiology. Significantly, gradual progress is being made in the development of more sophisticated microphysiologically relevant human-based OOC models that allow the studies of the key biophysiological aspects of specific tissues or organs, interactions between cells (parenchymal, vascular, and immune cells) and their extracellular matrix molecules, effects of native tissue architectures (geometry, dynamic flow or mechanical forces) on tissue functions, as well as unravelling the mechanism underlying tissue-specific diseases and drug testing. In this Progress Report, we discuss the different components of the immune system, as well as immune OOC platforms and immunocompetent OOC approaches that have simulated one or more components of the immune system. We also outline the challenges to recreate a fully functional tissue system in vitro with a focus on the incorporation of the immune system.

3D Printing metamaterials towards tissue engineering.

The rapid growth and disruptive potentials of three-dimensional (3D) printing demand further research for addressing fundamental fabrication concepts and enabling engineers to realize the capabilities of 3D printing technologies. There is a trend to use these capabilities to develop materials that derive some of their properties via their structural organization rather than their intrinsic constituents, sometimes referred to as mechanical metamaterials. Such materials show qualitatively different mechanical behaviors despite using the same material composition, such as ultra-lightweight, super-elastic, and auxetic structures. In this work, we review current advancements in the design and fabrication of multi-scale advanced structures with properties heretofore unseen in well-established materials. We classify the fabrication methods as conventional methods, additive manufacturing techniques, and 4D printing. Following a comprehensive comparison of different fabrication methods, we suggest some guidelines on the selection of fabrication parameters to construct meta-biomaterials for tissue engineering. The parameters include multi-material capacity, fabrication resolution, prototyping speed, and biological compatibility.

Anatomical and biomechanical evaluation of the tension band technique in patellar fractures.

Tension band wiring for patellar fractures is common, but some recent reports refer to disadvantages of this approach. Our anatomical and biomechanical study focused on use of tension band techniques in patellar fractures. The anatomy of the patella and tendon insertion was examined with knee magnetic resonance imaging (MRI) and correlated with the technical requirements of the tension band. Tension band wiring over tendinous tissue was simulated and calculated with a cyclic biomechanical test on cow patellae. According to tension band templating on the MRI section, Kirschner wire insertion was needed for the tension band to turn over the tendinous tissue. The tension band became more stable while turning over less tendinous tissue and more adjacent bone surface. Nevertheless, cyclic loading tests indicate that all tension band applications in this study lose their initial stability. Excessive initial compression by the tension band resulted in bending of the Kirschner wire and thus reduction failure. For optimum stabilisation, tension force transfer should be done directly on bone or at least material that protects the tendon would be useful.

Effects of simvastatin on matrix metalloproteinase regulation in IL-1ß-induced SW1353 cells.

The present study shows the basis for the anti-inflammatory effects of statins in interleukin 1ß (IL-1ß) induced SW1353 chondrosarcoma cell-line. The cells were pre-treated with simvastatin (5 µM, 10 µM, and 50 µM), followed by IL-1ß (5 ng/mL) stimulation. Effects of simvastatin on cell viability and cytotoxicity of chondrocytes were measured with WST-1 and lactate dehydrogenase (LDH) assays, respectively. Under inflammatory conditions, in the absence/presence of simvastatin, the changes in matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression levels were examined. Expression levels of MMP-1, -2, -3, -9, -13, and TIMP-1 and -2 were examined by qPCR. MMP-1, -9, -13, TIMP-1, and -2 levels were also determined by Western blotting. Gelatin zymography was performed to analyze the released and intracellular MMP-2 and MMP-9 activity levels. The results showed that simvastatin downregulated the degradation related genes MMP-3, MMP-13, MMP-2, MMP-9 and TIMP-2 in a dose-dependent manner.

Production and Characterization of a Novel Bilayer Nanocomposite Scaffold Composed of Chitosan/Si-nHap and Zein/POSS Structures for Osteochondral Tissue Regeneration.

Osteochondral tissue is hard to regenerate after injuries or degenerative diseases. Traditional treatments still have disadvantages, such as donor tissue availability, donor site morbidity, implant loss, and limited durability of prosthetics. Thus, recent studies have focused on tissue engineering strategies to regenerate osteochondral defects with different scaffold designs. Scaffolds have been developed from monolayer structures to bilayer scaffolds to repair the cartilage-bone interface and to support each tissue separately. In this study, Si-substituted nanohydroxyapatite particles (Si-nHap) and silica-based POSS nanocages were used as reinforcements in different polymer layers to mimic a cartilage-bone tissue interface. Chitosan and zein, which are widely used biopolymers, are used as polymer layers to mimic the structure. This study reports the development of a bilayer scaffold produced via fabrication of two different nanocomposite layers with different polymer-inorganic composites in order to satisfy the complex and diverse regenerative requirements of osteochondral tissue. The chitosan/Si-nHap microporous layer and the zein/POSS nanofiber layer were designed to mimic a bone-cartilage tissue interface. Bilayer scaffolds were characterized with SEM, compression, swelling, and biodegradation tests to determine morphological, physical, and mechanical properties. The results showed that the bilayer scaffold had a structure composed of microporous and nanofiber layers joined at a continuous interface with appropriate mechanical properties. Furthermore, in vitro cell culture studies have been performed with LDH, proliferation, fluorescence imaging, and ALP activity assays using osteosarcoma and chondrosarcoma cell lines. ALP expression levels provide a good illustration of the improved osteogenic potential of a porous chitosan/Si-nHap layer due to the Si-doped nHap incorporation. Histological data showed that both fiber and porous layers that mimic the cartilage and bone sections exhibit homogeneous cell distribution and matrix formation. Histochemical staining was used to determine the cell proliferation and ECM formation on each layer. In vitro studies indicated that zein-POSS/chitosan/Si-nHap nanocomposite bilayer scaffolds showed promising results for osteochondral regeneration.

Multiscale bioprinting of vascularized models.

A basic prerequisite for the survival and function of three-dimensional (3D) engineered tissue constructs is the establishment of blood vessels. 3D bioprinting of vascular networks with hierarchical structures that resemble in vivo structures has allowed blood circulation within thick tissue constructs to accelerate vascularization and enhance tissue regeneration. Successful rapid vascularization of tissue constructs requires synergy between fabrication of perfusable channels and functional bioinks that induce angiogenesis and capillary formation within constructs. Combinations of 3D bioprinting techniques and four-dimensional (4D) printing concepts through patterning proangiogenic factors may offer novel solutions for implantation of thick constructs. In this review, we cover current bioprinting techniques for vascularized tissue constructs with vasculatures ranging from capillaries to large blood vessels and discuss how to implement these approaches for patterning proangiogenic factors to maintain long-term, stimuli-controlled formation of new capillaries.