Modelling of macrophage responses to biomaterials in vitro: state-of-the-art and the need for the improvement.

The increasing use of medical implants in various areas of medicine, particularly in orthopedic surgery, oncology, cardiology and dentistry, displayed the limitations in long-term integration of available biomaterials. The effective functioning and successful integration of implants requires not only technical excellence of materials but also consideration of the dynamics of biomaterial interaction with the immune system throughout the entire duration of implant use. The acute as well as long-term decisions about the efficiency of implant integration are done by local resident tissue macrophages and monocyte-derived macrophages that start to be recruited during tissue damage, when implant is installed, and are continuously recruited during the healing phase. Our review summarized the knowledge about the currently used macrophages-based in vitro cells system that include murine and human cells lines and primary ex vivo differentiated macrophages. We provided the information about most frequently examined biomarkers for acute inflammation, chronic inflammation, foreign body response and fibrosis, indicating the benefits and limitations of the model systems. Particular attention is given to the scavenging function of macrophages that controls dynamic composition of peri-implant microenvironment and ensures timely clearance of microorganisms, cytokines, metabolites, extracellular matrix components, dying cells as well as implant debris. We outline the perspective for the application of 3D systems for modelling implant interaction with the immune system in human tissue-specific microenvironment avoiding animal experimentation.

Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it.

Strategies to enhance the ability of nerve guidance conduits to promote directional nerve growth.

Severely damaged peripheral nerves will regenerate incompletely due to lack of directionality in their regeneration, leading to loss of nerve function. To address this problem, various nerve guidance conduits (NGCs) have been developed to provide guidance for nerve repair. However, their clinical application is still limited, mainly because its effect in promoting nerve repair is not as good as autologous nerve transplantation. Therefore, it is necessary to enhance the ability of NGCs to promote directional nerve growth. Strategies include preparing various directional structures on NGCs to provide contact guidance, and loading various substances on them to provide electrical stimulation or neurotrophic factor concentration gradient to provide directional physical or biological signals.

Silicone implant surface microtopography modulates inflammation and tissue repair in capsular fibrosis.

Excessive fibrous capsule formation around silicone mammary implants (SMI) involves immune reactions to silicone. Capsular fibrosis, a common SMI complication linked to host responses, worsens with specific implant topographies. Our study with 10 patients investigated intra- and inter-individually, reduced surface roughness effects on disease progression, wound responses, chronic inflammation, and capsular composition. The results illuminate the significant impact of surface roughness on acute inflammatory responses, fibrinogen accumulation, and the subsequent fibrotic cascade. The reduction of surface roughness to an average roughness of 4 µm emerges as a promising approach for mitigating detrimental immune reactions, promoting healthy wound healing, and curbing excessive fibrosis. The identified proteins adhering to rougher surfaces shed light on potential mediators of pro-inflammatory and pro-fibrotic processes, further emphasizing the need for meticulous consideration of surface design. The composition of the implant capsule and the discovery of intracapsular HSP60 expression highlight the intricate web of stress responses and immune activation that can impact long-term tissue outcomes.

Quantitative noninvasive measurement of cerebrospinal fluid flow in shunted hydrocephalus.

OBJECTIVE: Standard MRI protocols lack a quantitative sequence that can be used to evaluate shunt-treated patients with a history of hydrocephalus. The objective of this study was to investigate the use of phase-contrast MRI (PC-MRI), a quantitative MR sequence, to measure CSF flow through the shunt and demonstrate PC-MRI as a useful adjunct in the clinical monitoring of shunt-treated patients. METHODS: The rapid (96 seconds) PC-MRI sequence was calibrated using a flow phantom with known flow rates ranging from 0 to 24 mL/hr. Following phantom calibration, 21 patients were scanned with the PC-MRI sequence. Multiple, successive proximal and distal measurements were gathered in 5 patients to test for measurement error in different portions of the shunt system and to determine intrapatient CSF flow variability. The study also includes the first in vivo validations of PC-MRI for CSF shunt flow by comparing phase-contrast-measured flow rate with CSF accumulation in a collection burette obtained in patients with externalized distal shunts. RESULTS: The PC-MRI sequence successfully measured CSF flow rates ranging from 6 to 54 mL/hr in 21 consecutive pediatric patients. Comparison of PC-MRI flow measurement and CSF volume collected in a bedside burette showed good agreement in a patient with an externalized distal shunt. Notably, the distal portion of the shunt demonstrated lower measurement error when compared with PC-MRI measurements acquired in the proximal catheter. CONCLUSIONS: The PC-MRI sequence provided accurate and reliable clinical measurements of CSF flow in shunt-treated patients. This work provides the necessary framework to include PC-MRI as an immediate addition to the clinical setting in the noninvasive evaluation of shunt function and in future clinical investigations of CSF physiology.

Torque forces of expandable titanium vertebral body replacement cages during expansion and subsidence in the osteoporotic lumbar spine.

BACKGROUND: The application of expandable titanium-cages has gained widespread use in vertebral body replacement for indications such as burst fractures, tumors and infectious destruction. However, torque forces necessary for a satisfactory expansion of these implants and for subsidence of them into the adjacent vertebrae are unknown within the osteoporotic spine. METHODS: Six fresh-frozen human, osteoporotic, lumbar spines were dorsally instrumented with titanium implants (L2-L4) and a partial corpectomy of L3 was performed. An expandable titanium-cage was inserted ventrally and expanded by both residents and senior surgeons until fixation was deemed sufficient, based on haptic feedback. Torque forces for expansion were measured in Nm. Expansion was then continued until cage subsidence occurred. Torque forces necessary for subsidence were recorded. Strain of the dorsal rods during expansion was measured with strain gauges. FINDINGS: The mean torque force for fixation of cages was 1.17 Nm (0.9 Nm for residents, 1.4 Nm for senior surgeons, p = .06). The mean torque force for subsidence of cages was 3.1 Nm (p = .005). Mean peak strain of the dorsal rods was 970 µm/m during expansion and 1792 µm/m at subsidence of cages (p = .004). INTERPRETATION: The use of expandable titanium-cages for vertebral body replacement seems to be a primarily safe procedure even within the osteoporotic spine as torque forces required for subsidence of cages are nearly three times higher than those needed for fixation. Most of the expansion load is absorbed by straining of the dorsal instrumentation. Rod materials other than titanium may alter the torque forces found in this study.

Prosthetic Nasal Reconstruction.

Prosthetic nasal reconstruction provides a restorative option for patients with nasal defects, and these can be retained with a variety of methods including adhesives and implants. These prostheses can significantly improve appearance, self-esteem, and quality of life for patients and they restore many functions of the external nose. Traditional fabrication methods are often used by the skilled professionals who make these custom prostheses, but digital technology is improving the workflow for design and fabrication of silicone nasal prostheses. Nasal prosthetic reconstruction requires multidisciplinary coordination between surgeons, maxillofacial prosthodontists, anaplastologists, and other members of the healthcare team. Prosthetic treatment can be considered as an alternative to, or an addition to treatment with surgical reconstruction.

In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study.

Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.

In a porcine model of implantable pacemakers for pediatric unilateral diaphragm paralysis, the phrenic nerve is the best target.

BACKGROUND: A frequent complication of Fontan operations is unilateral diaphragmatic paresis, which leads to hemodynamic deterioration of the Fontan circulation. A potential new therapeutic option is the unilateral diaphragmatic pacemaker. In this study, we investigated the most effective stimulation location for a potential fully implantable system in a porcine model. METHODS: Five pigs (20.8 ± 0.95 kg) underwent implantation of a customized cuff electrode placed around the right phrenic nerve. A bipolar myocardial pacing electrode was sutured adjacent to the motor point and peripherally at the costophrenic angle (peripheral diaphragmatic muscle). The electrodes were stimulated 30 times per minute with a pulse duration of 200 µs and a stimulation time of 300 ms. Current intensity was the only variable changed during the experiment. RESULTS: Effective stimulation occurred at 0.26 ± 0.024 mA at the phrenic nerve and 7 ± 1.22 mA at the motor point, a significant difference in amperage (p = 0.005). Even with a maximum stimulation of 10 mA at the peripheral diaphragm muscle, however, no effective stimulation was observed. CONCLUSION: The phrenic nerve seems to be the best location for direct stimulation by a unilateral thoracic diaphragm pacemaker in terms of the required amperage level in a porcine model.

Severe Hemodynamic Collapse During Humerus Stabilization with Photodynamic Implant: A Report of Two Cases.

CASE: We present 2 cases of severe hemodynamic collapse during prophylactic stabilization of impending pathologic humerus fractures using a photodynamic bone stabilization device. Both events occurred when the monomer was infused under pressure into a balloon catheter. CONCLUSION: We suspect that an increase in intramedullary pressure during balloon expansion may cause adverse systemic effects similar to fat embolism or bone cement implantation syndrome. Appropriate communication with the anesthesia team, invasive hemodynamic monitoring, and prophylactic vent hole creation may help mitigate or manage these adverse systemic effects.

[Exploration of Application of Reliability Standard YY/T 1837-2022 in Development of Active Implantable Medical Devices].

In the field of medical devices, there has been a long-term lack of a general technical requirements framework for reliability that can be applied in the development of high-risk active implantable medical devices. This study combines the requirements of YY/T 1837-2022 to comprehensively explain and explore the requirements for reliability work that can be performed at each stage of development of active implantable medical device products, and provides a reference for product reliability work in the industry.

[Medical and social aspects of testicular prosthetics in adults and adolescents].

Despite a long history and seeming simplicity, testicular prosthesis is associated with a lot of unresolved issues. As new publications appear, the sharpness of the discussion around issues related to prosthetics does not tend to decrease. The review is based on publications on testicular prosthesis in adolescence and adulthood published in PubMed databases (https://www.ncbi.nlm.nih.gov/pubmed/) and Scientific Electronic Library Elibrary.ru (https://elibrary.ru/) was done. Only articles published in peer-reviewed journals were selected. The search was carried out using the following keywords: "testicular prosthesis", "structure of patients", "social rehabilitation", "social adaptation", "complications", "repeated implantation of testicular prosthesis". A total of 146 sources have been identified (predominantly over the past 10 years), and 44 have the highest scientific value and have been selected for citation and analysis. Testicular prosthesis is an important component of the psychological and physical well-being of the patient after orchiectomy, normalization of reproductive function and sexual adaptation [1, 2]. A body defect that occurs after an orchiectomy is in most cases perceived as a psychologic trauma. The evaluation of the results by both specialists and patients certainly deserves serious attention, but the works dedicated to this issue in detail are sparse, contradictory and do not fully disclose the problem. Many issues related to testicular prosthesis remain open for discussion. There is a trend in clarification of the optimal age of the intervention, surgical technique and complications. The evaluation of the results from both a professional point of view and the patient's perception and satisfaction is currently far from being resolved, therefore, such studies are still relevant.

Ultrasound-Assisted Spinal Anesthesia in a Patient with a Preexisting Lumbar Interspinous Spacer: A Case Report.

An interspinous spacer is a minimally invasive implantable device for the treatment of lumbar spinal stenosis. The in situ implant may prevent safe and successful spinal anesthesia because its position can obstruct the path of the spinal needle. Lumbar neuraxial ultrasonography has been shown to aid in performance of neuraxial anesthesia in patients with challenging anatomy. Currently, there are no reported cases of ultrasound-assisted spinal anesthesia in patients with interspinous spacers. We present a case in which ultrasonography assisted the successful administration of a spinal anesthetic by avoiding an indwelling lumbar interspinous spacer.

Infección de prótesis aórtica abdominal: tratamiento alternativo / Infected abdominal aortic prosthesis: an alternative therapy

Introducción: la infección de prótesis aórtica en la cirugía vascular convencional es un evento catastrófico, con una alta tasa de morbilidad y de mortalidad. El tratamiento tradicional ha sido la remoción de la prótesis y la reconstrucción con bypass extraanatómico. En algunos casos, se ha llevado a cabo el reemplazo con prótesis impregnadas en antibiótico; en otros, el reemplazo con vena femoral superficial y también la cirugía abierta con drenaje de las colecciones asociadas y antibioticoterapia de por vida. Caso clínico: se presenta el reporte de un caso de infección protésica tratada con drenajes de las colecciones y antibioticoterapia de larga duración, con un resultado favorable un año después de su complicación. Discusión: en algunos casos, dada la severidad del paciente, es posible intentar un tratamiento conservador de esta nefasta complicación.(AU)

Introduction: in traditional vascular surgery, aortic prosthesis infection is a catastrophic event with high morbidity andmortality rates. Traditional treatment is the removal of the valve followed by extra-anatomic bypass reconstruction. Insome cases, antibiotic-impregnated prosthesis replacement has been performed. In others, superficial femoral veinreplacement, and open surgery with drainage of the associated collections and lifelong antibiotic therapy.Case report: this is the case of a patient with aortic prosthesis infection undergoing draining collections and lifelongantibiotic therapy with a favorable outcome 1 year after the complication.Discussion: in some cases, given the severity of the patient, we can try to treat this dreaded complication conservativel.(AU)

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing.

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors mainly requires transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces biocompatibility, or limits portability. Here, we develop a set of millimeter-scale, chip-less, and battery-less magnetic implants paired with a fully integrated wearable device for measuring biophysical and biochemical signals. The wearable device can induce a large amplitude damped vibration of the magnetic implants and capture their subsequent motions wirelessly. These motions reflect the biophysical conditions surrounding the implants and the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities of measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure, and CSF glucose levels. This miniaturized system opens the possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

[Choice of the prosthetic valve in patients aged between 55 and 70 years]. / Scelta della protesi valvolare nei pazienti di età 55-70 anni.

About 280 000 heart valve replacements are performed worldwide every year. Since the first prosthetic valve implantation in 1952 there have been notable developments. There are a lot of types of prosthetic valves that can be summarized into two categories: biological prosthetic valves or mechanical prosthetic valves. Biological prostheses, made of bovine or porcine pericardium, homografts, or autografts, degenerate over time becoming dysfunctional. Mechanical prostheses have a potentially unlimited lifespan but require oral anticoagulation which can affect patients' quality of life. Generally, biological prostheses are particularly suitable for elderly patients while mechanical prostheses for young people, with some distinctions. For example, in case of age <60 years, in the presence of preoperative oral anticoagulant therapy, metabolic syndrome, hemodialysis or hyperparathyroidism, a mechanical valve is the preference. The choice of the prosthesis in patients aged between 55 and 70 years is particularly challenging because the advantages and disadvantages of the two categories of prosthesis overlap in middle-aged patients. The choice of the prosthesis should be made after discussion with the surgeon, according to the patient's preferences, and keeping in mind the pros and cons of biological and mechanical prostheses.

Additively-manufactured Mg wire-reinforced PLDL-matrix composites for biomedical applications.

Coupons of a medical grade PLDL polymer matrix uniaxially reinforced with a 15% volume fraction of Mg wires have been manufactured by fused filament fabrication for the first time. Two different types of Mg wires, without and with a surface treatment by plasma electrolytic oxidation were used. Both composite materials were subjected to degradation in phosphate buffer solution over a 3-week period, and their degradation and deformation micromechanisms were analysed in detail. Additionally, the materials were subjected to extensive mechanical testing under various loading conditions, and the interface strength was also analysed. It was found that the presence of the Mg wires improves the mechanical behaviour and accelerates the corrosion rate of the composite with respect that of the polymer matrix and these properties can be further tailored through the surface-modification of Mg wires by plasma electrolytic oxidation. The additive manufacturing strategy presented opens the path to fabricate multimaterial implants and scaffolds with complex shape and tailored properties provided by biodegradable polymers reinforced with either Mg and Zn particles and/or wires.