Tissue Interface Research Articles

A Murine Model of Non-Wear-Particle-Induced Aseptic Loosening

Background: The current murine models of peri-implant osseointegration failure are associated with wear particles. However, the current clinical osseointegration failure is not associated with wear particles. Here, we develop a murine model of osseointegration failure not associated with wear particles and validate it by comparing the cellular composition of interfacial tissues with human samples collected during total joint arthroplasty revision for aseptic loosening. Materials and Methods: Thirty-two 16-week-old female C57BL/6 mice underwent implantation with a press-fitted roughened titanium implant (Control, n = 11) to induce normal osseointegration and a press-fitted smooth polymethylmethacrylate implant (PMMA, n = 11), a loosely fitted smooth titanium implant (Smooth-Ti, n = 5) or a loosely fitted roughened titanium implant (Overdrill, n = 5) to induce osseointegration failure. Pullout testing was used to determine the strength of the bone–implant interface (n = 6 of each for Control and PMMA groups) at 2 weeks after implantation. Histology (n = 2/group) and immunofluorescence (n = 3/group) were used to determine the cellular composition of bone–implant interfacial tissue, and this was compared with two human samples. Results: Osseointegration failure was confirmed with grossly loosening implants and the presence of fibrous tissue identified via histology. The maximum pullout load in the PMMA group was 87% lower than in the Control group (2.8 ± 0.6 N vs. 21 ± 1.5 N, p < 0.001). With immunofluorescence, abundant fibroblasts (PDGFRα+ TCF4+ and PDGFRα+ Pu1+) were observed in osseointegration failure groups and the human samples, but not in controls. Interestingly, CD146+PDGFRα+ and LepR+PDGFRα+ mesenchymal progenitors, osteoblasts (OPN+), vascular endothelium (EMCN+) cells were observed in all groups, indicating dynamic osteogenic activity. Macrophages, only M2, were observed in conditions producing fibrous tissue. Conclusions: In this newly developed non-wear-particle-related murine osseointegration failure model, the cellular composition of human and murine interfacial tissue implicates specific populations of fibroblasts in fibrous tissue formation and implies that these cells may derive from mesenchymal stem cells.

Characterization of Disrupted Tissue Interface Thickness for Keratorefractive Lenticule Extraction Procedure With ELITA Femtosecond Laser.

This study identified and compared variables causing changes in corneal tissue structure following the smooth incision lenticular keratomileusis (SILK) procedure using the ELITA Femtosecond Laser System by characterizing the resulting disrupted tissue interface. Seventy-one ex vivo porcine eyes and six human cadaver eyes underwent ELITA SILK with diverse surgical steps, pulse energies, scan overlaps, and surgical methods. Flaps created with the iFS Advanced Femtosecond Laser and ELITA systems were also evaluated. The disrupted interface thickness was determined by imaging corneal layers at different depths through the interface with confocal microscopy and counting layers with elevated backscattered light via computer program-assisted, subject-matter-expert visual judgment with blinding. The disrupted interface thickness for ELITA SILK was 25 ± 3 µm; for the ELITA flap, it was 25 ± 2 µm; and for the iFS flap, it was 32 ± 3 µm. Factors influencing the total ELITA SILK disrupted interface thickness included laser pulse energy (0.11µm/nJ; P < 0.01), scan overlap (5µm; P < 0.01), and mechanical manipulation (7µm; P < 0.01). Varying surgical techniques for mechanical manipulation resulted in a difference in disrupted interface thickness of 4µm (P < 0.01). The ELITA SILK disrupted interface thickness was less than that of the iFS flap and similar to that of the ELITA flap. Assessing disrupted interface thickness identified factors influencing the quality of the corneal interface with SILK. The disrupted interface thickness, a new method for measuring corneal damage, has been used to quantify the potential effects of various refractive surgery factors on surgical outcomes.

Branched-chain amino acid catabolism promotes ovarian cancer cell proliferation via phosphorylation of mTOR.

This study uncovers altered amino acid metabolism, specifically increased BCAA catabolism, at the interface of ovarian cancer cells and omental tissue in a coculture model of HGSOC secondary metastasis. Enhanced BCAA catabolism may promote cancer cell proliferation through mTOR signaling, presenting potential therapeutic value. These findings deepen our understanding of HGSOC pathogenesis and the metastatic tumor microenvironment, offering insights for developing new treatment strategies.

Preliminary study on Cyclocodon lancifolius leaf blight and screening of Bacillus subtilis as a biocontrol agent.

This study aimed to identify the pathogen responsible for leaf blight in Cyclocodon lancifolius, investigate its biological characteristics, and identify effective synthetic fungicides. Additionally, this study examined changes in physiological and biochemical indices of leaves following pathogen infection and screened biocontrol bacteria that inhibit the pathogen growth, providing a scientific basis for preventing and managing leaf blight in C. lancifolius. Pathogens were isolated from the interface of healthy and infected leaf tissues and identified through morphological and molecular biological methods. Amplification and sequencing of three genomic DNA regions-internal transcribed spacer region, translation elongation factor 1-α, and glyceraldehyde-3-phosphate dehydrogenase of ribosomal DNA-were performed, followed by the construction of a phylogenetic tree. The biological characteristics of pathogens under various temperature and pH conditions and different nitrogen and carbon sources were analyzed using the mycelial growth rate method. The antifungal effects of 13 chemical agents were evaluated using the poisoned medium method and mycelial growth rate method. Changes in physiological and biochemical indicators post-infection were also assessed. An antagonistic experiment was conducted to screen for biocontrol bacteria. A total of 29 potential pathogenic strains were isolated from infected leaf tissues, with Koch's Postulates confirming Stemphylium lycopersici as a key pathogen causing the disease. Growth analysis of S. lycopersici revealed optimal growth at 20°C and pH 6, with lactose or maltose serving as the most suitable carbon source and histidine as the preferred nitrogen source. Among the 13 synthetic fungicides tested, strain DHY4 exhibited the greatest sensitivity to 400 g/L flusilazole. Significant differences (p < 0.05) were observed in superoxide dismutase, phenylalanine ammonia-lyase, peroxidase, polyphenol oxidase, catalase, and malondialdehyde levels between treated and control groups 3 days post-inoculation. The biocontrol strain DYHS2, identified as a strain of Bacillus subtilis, demonstrated an inhibition rate of 51.80% against S. lycopersici in dual-culture experiments and showed a relative inhibition rate of 78.82% in detached leaf assays. These findings provide valuable insights into the newly identified causal agent of leaf blight in C. lancifolius and its biological characteristics, underscoring the potential of B. subtilis DYHS2 and synthetic fungicides such as flusilazole as effective disease management strategies.

Shaping the mechanical properties of a gelatin hydrogel interface via amination.

Injuries to musculoskeletal interfaces, such as the tendon-to-bone insertion of the rotator cuff, present significant physiological and clinical challenges for repair due to complex gradients of structure, composition, and cellularity. Advances in interface tissue engineering require stratified biomaterials able to both provide local instructive signals to support multiple tissue phenotypes while also reducing the risk of strain concentrations and failure at the transition between dissimilar materials. Here, we describe adaptation of a thiolated gelatin (Gel-SH) hydrogel via selective amination of carboxylic acid subunits on the gelatin backbone. The magnitude and kinetics of HRP-mediated primary crosslinking and carbodiimide-mediated secondary crosslinking reactions can be tuned through amination and thiolation of carboxylic acid subunits on the gelatin backbone. We also show that a stratified biomaterial comprised of mineralized (bone-mimetic) and non-mineralized (tendon-mimetic) collagen scaffold compartments linked by an aminated Gel-SH hydrogel demonstrate improved mechanical performance and reduced strain concentrations. Together, these results highlight significant mechanical advantages that can be derived from modifying the gelatin macromer via controlled amination and thiolation and suggest an avenue for tuning the mechanical performance of hydrogel interfaces within stratified biomaterials.

Suspended Tissue Open Microfluidic Patterning (STOMP).

Cell-laden hydrogel constructs suspended between pillars are powerful tools for modeling tissue structure and physiology, though current fabrication techniques often limit them to uniform compositions. In contrast, tissues are complex in nature with spatial arrangements of cell types and extracellular matrices. Thus, we present Suspended Tissue Open Microfluidic Patterning (STOMP), which utilizes a removable, open microfluidic patterning channel to pattern multiple spatial regions across a single suspended tissue. The STOMP platform contains capillary pinning features along the open channel that controls the fluid front, allowing multiple cell and extracellular matrix precursors to be pipetted into one tissue. We have used this technique to pattern suspended tissues with multiple regional components using a variety of native and synthetic extracellular matrices, including fibrin, collagen, and poly(ethylene glycol). Here, we demonstrate that STOMP models a region of fibrosis in a functional heart tissue and a bone-ligament junction in periodontal tissues. Additionally, the STOMP platform can be customized to allow patterning of suspended cores and more spatial configurations, enhancing its utility in complex tissue modeling. STOMP is a versatile technique for generating suspended tissue models with increased control over cell and hydrogel composition to model interfacial tissue regions in a suspended tissue.

The Effect of Ethanol on Rotator Cuff Repairs in a Rodent Model

BackgroundAlcohol consumption is a significant risk factor for both the occurrence and severity of rotator cuff tears. However, there is limited supporting evidence to suggest alcohol use is associated with suboptimal outcomes following operative repair of rotator cuff tears. Rat shoulders have been demonstrated as consistent and reliable models for studying rotator cuff disease. Hypothesis/PurposePerioperative alcohol exposure will negatively impact biomechanical and histologic properties of surgically repaired rotator cuffs in rats. MethodsRats were randomized to receive a 20% ethanol or isocaloric control solution as their primary source of drinking water. A tenotomy of the supraspinatus tendon from bone was performed surgically and then immediately repaired with a transosseous technique. Following surgery, rats were continued on the same exposure solution until animals were humanely euthanized at 7, 14, or 21 days postoperatively. The surgically-repaired shoulders underwent biomechanical testing to assess load to failure and failure strain. Histological evaluation of tendon-to-bone healing was performed by a blinded pathologist using a qualitative grading system. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on total RNA from tendon-to-bone interface tissue was performed to quantify the mRNA expression of Type I & III collagen, and transforming growth factor-beta 1 (TGF-B1) & 3 (TGF-B3) at the repair site. ResultsBiomechanical testing showed that repaired shoulder constructs in rats exposed to ethanol had significantly lower load to failure at 7 days postop relative to repairs in rats exposed to a control solution. No other biomechanical parameters or time points reached statistical significance. TGF-B3 mRNA expression was found in significantly higher quantities at the repair sites of rats exposed to ethanol at 7 days postop relative to control rat repair sites. No other time points or factors reached statistical significance. No significant differences were identified amongst time points or groups at the healing tendon-to-bone interface. ConclusionAlcohol exposure significantly decreases biomechanical load to failure of rotator cuff repairs in the early postoperative period in rat models. In the later postoperative period, alcohol exposure was not associated with a decrease in biomechanical load to failure compared to controls. Additionally, rats exposed to ethanol have significantly higher TGF-B3 expression at repair sites on postoperative day 7. This data suggests that ethanol consumption does deleteriously affect rotator cuff and bone healing. Future study is needed to validate the clinical significance of these findings in humans.

Advances in Additive Manufactured Scaffolds Mimicking the Osteochondral Interface

Architectural, compositional, and mechanical gradients are present in many interfacial tissues in the body. Yet desired for regeneration, the recreation of these complex natural gradients in porous scaffolds remains a challenging task. Additive manufacturing (AM) has been highlighted as a technology to fabricate constructs to regenerate interfacial tissues. Integration of different types of gradients, which can be physical, mechanical, and/or biochemical, shows promise to control cell fate and the regeneration process in a spatial controlled manner. One of the most studied tissue interfaces is the osteochondral unit which connects cartilage to bone. This tissue is often damaged because of trauma or ageing, leading to osteoarthritis; a degenerative disease and a major cause of disability worldwide. Therefore, in view of osteochondral (OC) regeneration, a state‐of‐the‐art overview of current approaches is presented to manufacture gradient scaffolds prepared by AM techniques. The focus is on thermoplastic, hydrogel, and hybrid scaffolds comprising gradients that induce biomimicry by their physical and biological properties. The effect of these different systems on OC tissue formation in‐vitro and in‐vivo is addressed. Finally, an outlook on current trends of dynamic materials is provided, including proposals on how these materials could improve the mimicry of scaffolds applied for OC regeneration.

Enhanced osseointegration and antimicrobial properties of 3D-Printed porous titanium alloys with copper-strontium doped calcium silicate coatings.

The 3D printing of porous titanium scaffolds reduces the elastic modulus of titanium alloys and promotes osteogenic integration. However, due to the biological inertness of titanium alloy materials, the implant-bone tissue interface is weakly bonded. A calcium silicate (CS) coating doped with polymetallic ions can impart various biological properties to titanium alloy materials. In this study, CuO and SrO binary-doped CS coatings were prepared on the surface of 3D-printed porous titanium alloy scaffolds using atmospheric plasma spraying and characterized by SEM, EDS, and XRD. Both CuO and SrO were successfully incorporated into the CS coating. The in vivo osseointegration evaluation of the composite coating-modified 3D-printed porous titanium alloy scaffolds was conducted using a rabbit bone defect model, showing that the in vivo osseointegration of 2% CuO-10% SrO-CS-modified 3D-printed porous titanium alloy was improved. The in vitro antimicrobial properties of the 2% CuO-10% SrO-CS-modified 3D-printed porous titanium alloy were evaluated through bacterial platform coating, co-culture liquid absorbance detection, and crystal violet staining experiments, demonstrating that the composite coating exhibited good antimicrobial properties. In conclusion, the composite scaffold possesses both osteointegration-promoting and antimicrobial properties, indicating a broad potential for clinical applications.

Automated Microfluidics-Assisted Hydrogel-Based Wet-Spinning for the Biofabrication of Biomimetic Engineered Myotendinous Junction.

The muscle-tendon junction (MTJ) plays a pivotal role in efficiently converting the muscular contraction into a controlled skeletal movement through the tendon. Given its complex biomechanical intricacy, the biofabrication of such tissue interface represents a significant challenge in the field of musculoskeletal tissue engineering. Herein, a novel method to produce MTJ-like hydrogel yarns using a microfluidics-assisted 3D rotary wet-spinning strategy is developed. Optimization of flow rates, rotational speed, and delivery time of bioinks enables the production of highly compartmentalized scaffolds that recapitulate the muscle, tendon, and the transient MTJ-like region. Additionally, such biofabrication parameters are validated in terms of cellular response by promoting an optimal uniaxial alignment for both muscle and tendon precursor cells. By sequentially wet-spinning C2C12 myoblasts and NIH 3T3 fibroblasts, a gradient-patterned cellular arrangement mirroring the intrinsic biological heterogeneity of the MTJ is successfully obtained. The immunofluorescence assessment further reveals the localized expression of tissue-specific markers, including myosin heavy chain and collagen type I/III, which demonstrate muscle and tenogenic tissue maturation, respectively. Remarkably, the muscle-tendon transition zone exhibits finger-like projection of the multinucleated myotubes in the tenogenic compartment, epitomizing the MTJ signature architecture.

Quantifying physical degradation alongside recording and stimulation performance of 980 intracortical microelectrodes chronically implanted in three humans for 956-2246 days.

The clinical success of brain-machine interfaces depends on overcoming both biological and material challenges to ensure a long-term stable connection for neural recording and stimulation. Therefore, there is a need to quantify any damage that microelectrodes sustain when they are chronically implanted in the human cortex. Using scanning electron microscopy (SEM), we imaged 980 microelectrodes from Neuroport arrays chronically implanted in the cortex of three people with tetraplegia for 956-2246 days. We analyzed eleven multi-electrode arrays in total: eight arrays with platinum (Pt) electrode tips and three with sputtered iridium oxide tips (SIROF); one Pt array was left in sterile packaging, serving as a control. The arrays were implanted/explanted across three different clinical sites surgeries (Caltech/UCLA, Caltech/USC and APL/Johns Hopkins) in the anterior intraparietal area, Brodmann's area 5, motor cortex, and somatosensory cortex.Human experts rated the electron micrographs of electrodes with respect to five damage metrics: the loss of metal at the electrode tip, the amount of separation between the silicon shank and tip metal, tissue adherence or bio-material to the electrode, damage to the shank insulation and silicone shaft. These metrics were compared to functional outcomes (recording quality, noise, impedance and stimulation ability). Despite higher levels of physical degradation, SIROF electrodes were twice as likely to record neural activity than Pt electrodes (measured by SNR), at the time of explant. Additionally, 1 kHz impedance (measured in vivo prior to explant) significantly correlated with all physical damage metrics, recording, and stimulation performance for SIROF electrodes (but not Pt), suggesting a reliable measurement of in vivo degradation.We observed a new degradation type, primarily occurring on stimulated electrodes ("pockmarked" vs "cracked") electrodes; however, tip metalization damage was not significantly higher due to stimulation or amount of charge. Physical damage was centralized to specific regions of an array often with differences between outer and inner electrodes. This is consistent with degradation due to contact with the biologic milieu, influenced by variations in initial manufactured state. From our data, we hypothesize that erosion of the silicon shank often precedes damage to the tip metal, accelerating damage to the electrode / tissue interface. These findings link quantitative measurements, such as impedance, to the physical condition of the microelectrodes and their capacity to record and stimulate. These data could lead to improved manufacturing or novel electrode designs to improve long-term performance of BMIs making them are vitally important as multi-year clinical trials of BMIs are becoming more common.

Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque

Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human IGF1 (hIGF1). Nanoparticle-mediated placental overexpression of hIGF1 in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth. The objective of this pilot study was to extend these studies to the pregnant nonhuman primate and develop a method for local delivery of nanoparticles to the placenta via maternal blood flow from the uterine artery. Nanoparticles containing hIGF1 plasmid driven by the placenta-specific PLAC1 promoter were delivered to a mid-gestation pregnant rhesus macaque via a catheterization approach that is clinically used for uterine artery embolization. Maternal-fetal interface, fetal and maternal tissues were collected four days post-treatment to evaluate the efficacy of hIGF1 treatment in the placenta. The uterine artery catheterization procedure and nanoparticle treatment was well tolerated by the dam and fetus through the four-day study period following catheterization. Nanoparticles were taken up by the placenta from maternal blood as plasmid-specific hIGF1 expression was detected in multiple regions of the placenta via in situ hybridization and qPCR. The uterine artery catheterization approach enabled successful delivery of nanoparticles to maternal circulation in close proximity to the placenta with no concerns to maternal or fetal health in this short-term feasibility study. In the future, this delivery approach can be used for preclinical evaluation of the long-term safety and efficacy of nanoparticle-mediated placental therapies in a rhesus macaque model.

Needle-Like Multifunctional Biphasic Microfiber for Minimally Invasive Implantable Bioelectronics.

Implantable bioelectronics has attracted significant attention in electroceuticals and clinical medicine for precise diagnosis and efficient treatment of target diseases. However, conventional rigid implantable devices face challenges such as poor tissue-device interface and unavoidable tissue damage during surgical implantation. Despite continuous efforts to utilize various soft materials to address such issues, their practical applications remain limited. Here, a needle-like stretchable microfiber composed of a phase-convertible liquid metal (LM) core and a multifunctional nanocomposite shell for minimally invasive soft bioelectronics is reported. The sharp tapered microfiber can be stiffened by freezing akin to a conventional needle to penetrate soft tissue with minimal incision. Once implanted in vivo where the LM melts, unlike conventional stiff needles, it regains soft mechanical properties, which facilitate a seamless tissue-device interface. The nanocomposite incorporating with functional nanomaterials exhibits both low impedance and the ability to detect physiological pH, providing biosensing and stimulation capabilities. The fluidic LM embedded in the nanocomposite shell enables high stretchability and strain-insensitive electrical properties. This multifunctional biphasic microfiber conforms to the surfaces of the stomach, muscle, and heart, offering a promising approach for electrophysiological recording, pH sensing, electrical stimulation, and radiofrequency ablation in vivo.

EFFECTIVE TREATMENT OF SINGLE-STAGE REVISION USING NON-CONTACT LOW FREQUENCY ULTRASONIC DEBRIDEMENT IN TREATING PERIPROSTHETIC JOINT INFECTIONS: A PROSPECTIVE CLINICAL STUDY

Traditional mechanical debridement can only remove visibly infected tissue and is unable to completely clear all the biofilm that hides within muscle crevices and nerves. This study aims to determine the results of single-stage revision using noncontact low frequency ultrasonic debridement in treating chronic periprosthetic joint infections (PJI).A prospective study of consecutive patients requiring single-stage revision for chronic PJI was performed since August 2021. After mechanical debridement, an 8‑mm handheld non‑contact low‑frequency ultrasound probe was used for ultrasonic debridement at a frequency of (25±5) kHz and power of 90% for 5 minutes. Each ultrasound lasted 10 seconds with 3‑seconds intervals. The probe was repeatedly sonicated among all soft tissue and bsingle interface. The distal femoral canal and the posterior capsule of the knee were fully sonicated with a special right‑angle probe. Chemical debridement was then performed to irrigation the whole operative area. Recurrence of infection, culture results and number of colonies 24 hours after ultrasonic debridement were recorded.A total of 45 patients (25 hips and 20 knees) were included and 43 of them (95.6%) were free of infection at a mean follow-up time of 29 months (24 to 33). There were no intraoperative complications related to ultrasonic debridement (neurovascular and muscle injury, poor wound healing and fat liquefaction). The culture‑positive rate of wound liquid before ultrasonic debridement was 40.0% (18/45), which significantly increased to 75.6% (34/45) after ultrasonic debridement (P=0.001). The median number of colonies 24 hours after ultrasonic debridement was 2372 CFU/ml (310 to 4340 CFU/ml), which was significantly higher than that before debridement (307 CFU/ml; 10 to 980 CFU/ml) (P=0.000).Single-stage revision with non‑contact low‑frequency ultrasonic debridement can fully expose bacteria within biofilm, increase the efficacy of chemical debridement and lead to a favorable short‑term outcome without related complications.

GRAPPA 2023 Debate: Is Psoriatic Disease Really a Primary Enthesitis That Drives Joint Synovitis? The Enthesitis Hypothesis 25 Years On.

The enthesitis hypothesis posits that enthesitis is a primary lesion and that inflammation at the enthesis initiates the musculoskeletal symptoms of psoriatic arthritis (PsA) and spondyloarthropathies (SpA). The hypothesis suggested that inflamed entheseal tissue near the synovium could trigger cytokine-mediated synovitis, that enthesis bone anchorage could explain osteitis, and that the location of entheses at the soft tissue interface could explain dactylitis. Advances in imaging techniques that allow better visualization of enthesitis lesions and the development of animal models have allowed evolution of the concept of enthesitis as a central mechanistic driver of musculoskeletal symptoms in PsA and SpA. A debate between Drs. Dennis McGonagle and Bruce Kirkham at the Group for Research on Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting discussed the data supporting and refuting this hypothesis in PsA and SpA, respectively. The major points of this debate are summarized in this article.

Unveiling the governing role of ‘remodeling triangle area’ in soft-hard tissue interface equilibrium for metal implants advancement

Metal implants holds significant promise for diverse fixed prostheses. However, their long-term reliability and broader application are hindered by challenges related to the disequilibrium at the soft-hard tissue interface. By using anti-inflammatory (PDA/IL4) and pro-inflammatory (PDA/LPS/IFNγ) coatings to modulate distinct immune characteristics, we discovered a dynamic bioactive structure at the soft-hard tissue interface around metal implant, which we have named the 'Remodeling Triangle Area' (RTA). We further demonstrate that the RTA can be influenced by the PDA/IL4 coating to favor a phenotype that enhances both innate and adaptive immunity. This leads to stronger epithelial adhesion, the formation of dense connective tissue via IGF1 secretion, and a more balanced soft-hard tissue interface through the OPG/RANKL axis. Conversely, the PDA/LPS/IFNγ coating shifts the RTA towards a phenotype that activates the innate immune response. This results in a less cohesive tissue structure and bone resorption, characterized by reduced IGF1 secretion and an imbalanced OPG/RANKL axis. Over all, our study introduces the novel concept termed the 'Remodeling Triangle Area' (RTA), an immune-rich anatomical region located at the nexus of the implant interface, epithelial, connective, and bone tissue, which becomes highly interactive post-implantation to modulate the soft-hard tissue interface equilibrium. We believe that an RTA-centric, immunomodulatory approach has the potential to revolutionize the design of next-generation metal implants, providing unparalleled soft-hard tissue interface equilibrium properties.

In situ bioprinting: Tailored printing strategies for regenerative medicine

&amp;nbsp;In recent years, three-dimensional (3D) bioprinting has emerged as a revolutionary biological manufacturing technology. Despite significant progress, current bioprinting technologies face critical barriers, such as the need for in vitro maturation of printed tissues before implantation and challenges of prefabricated structures not matching the defect shapes. In situ bioprinting has been introduced to address these challenges by printing customized structures to the wound shape via direct deposition of biological inks at the tissue interface. This paper reviews strategies to optimize printing performance for enhanced tissue repair and analyzes the advantages, challenges, and future directions of in situ bioprinting technologies.

Striated muscle fiber crossings of the head and neck: a histological study using near-term human fetuses and elderly cadavers.

Striated muscle fiber crossings at almost right angle are known to exist in the face, soft palate, pharyngeal wall and tongue. We aimed to identify a specific interface tissue at the crossing. We observed histological sections from 22 half-heads of 12 near-term fetuses at 26-40 weeks (crown-rump length, 215-334 mm). For comparison, we also observed tongue frontal sections from 5 elderly cadavers (75-85 years old). At the angle of mouth as well as in the soft palate and pharyngeal wall, a solitary striated muscle fiber (e.g., levator) consistently crossed a fiber bundle of the antagonist muscle (e.g., depressor), but a solitary-to-solitary fiber interdigitation was unlikely with the antagonist muscle. Near the external nasal orifice as well as in the tongue intrinsic muscle layer, at every section, there was a crossing with an endomysium-to-endomysium contact: the nasalis and platysma muscles and; the vertical and transverse (or inferior longitudinal) tongue muscles. Therein, the functional vectors crossed at almost right angle. Also in adult tongue, the vertical and transverse muscle fibers sometimes (0-2 sites per section) crossed with an endomysium-to-endomysium contact. At the muscle crossing with an endomysium contact, the endomysium and basement membrane seemed to receive a friction stress between two muscles. Although some crossings might disappear due to high muscle activity after birth, not a few of them were likely to maintain. To minimize the mechanical stress, a minute nervous control of the timing, duration and strength of muscle contraction seemed to be necessary.

Evaluating Virtual Contrast-Enhanced Magnetic Resonance Imaging in Nasopharyngeal Carcinoma Radiation Therapy: A Retrospective Analysis for Primary Gross Tumor Delineation

PurposeTo investigate the potential of virtual contrast-enhanced MRI (VCE-MRI) for gross-tumor-volume (GTV) delineation of nasopharyngeal carcinoma (NPC) using multi-institutional data. Methods and MaterialsThis study retrospectively retrieved T1-weighted (T1w), T2-weighted (T2w) MRI, gadolinium-based contrast-enhanced MRI (CE-MRI) and planning CT of 348 biopsy-proven NPC patients from three oncology centers. A multimodality-guided synergistic neural network (MMgSN-Net) was trained using 288 patients to leverage complementary features in T1w and T2w MRI for VCE-MRI synthesis, which was independently evaluated using 60 patients. Three board-certified radiation oncologists and two medical physicists participated in clinical evaluations in three aspects: image quality assessment of the synthetic VCE-MRI, VCE-MRI in assisting target volume delineation, and effectiveness of VCE-MRI-based contours in treatment planning. The image quality assessment includes distinguishability between VCE-MRI and CE-MRI, clarity of tumor-to-normal tissue interface and veracity of contrast enhancement in tumor invasion risk areas. Primary tumor delineation and treatment planning were manually performed by radiation oncologists and medical physicists, respectively. ResultsThe mean accuracy to distinguish VCE-MRI from CE-MRI was 31.67%; no significant difference was observed in the clarity of tumor-to-normal tissue interface between VCE-MRI and CE-MRI; for the veracity of contrast enhancement in tumor invasion risk areas, an accuracy of 85.8% was obtained. The image quality assessment results suggest that the image quality of VCE-MRI is highly similar to real CE-MRI. The mean dosimetric difference of planning target volumes were less than 1Gy. ConclusionsThe VCE-MRI is highly promising to replace the use of gadolinium-based CE-MRI in tumor delineation of NPC patients.

Dosimetric Impact of Prescription Point Placement in Heterogeneous Medium for Conformal Radiotherapy Dose Calculation with Various Algorithms

Objective: The aim of the study is to compare the accuracy of dose calculation for different dose calculation algorithms with different prescription points (air, tissue, air–tissue interface in carcinoma lung patients and bone, tissue, and bone–tissue interface in carcinoma buccal Mucosa tumors). Materials and Methods: Forty-one patients with carcinoma lung and buccal mucosa were retrospectively selected for this study. A three-dimensional conformal radiotherapy reference plan was created using the prescription point in the tissue with Monte Carlo (MC) algorithms for both the groups of patients. The reference plan was modified by changing the prescription point and algorithms in the tissue, air, air–tissue interface for lung patients and tissue, bone, and bone–tissue interface for buccal mucosa patients. The dose received by the target volume and other organs at risk (OAR) structures was compared. To find out the statistical difference between different prescription points and algorithms, the statistical tests were performed with repeated measures ANOVA. Results: The target volume receiving 95% dose coverage in lung patients decreased to −3.08%, −5.75%, and −1.87% in the dose prescription point at the air–tissue interface with the dose calculation algorithms like MC, collapsed cone (CC), and pencil beam (PB), respectively, compared to that of the MC tissue. Spinal cord dose was increased in the CC and PB algorithms in all prescription points in patients with lung and buccal mucosa. OAR dose calculated by PB in all prescription points showed a significant deviation compared to MC tissue prescription point. Conclusion: This study will help demonstrate the accuracy of dose calculation for the different dose prescription points with the different treatment algorithms in radiotherapy treatment planning.