Tissue Growth Research Articles

Melt electrowriting scaffolds with fibre-guiding features for periodontal attachment

Periodontal regeneration requires the re-attachment of oblique and perpendicular periodontal ligament (PDL) fibres to newly formed cementum and alveolar bone, which has proven elusive with existing approaches. In this study, multiple fibre-guiding biphasic tissue engineered constructs were fabricated by melt electrowriting. The biphasic scaffolds were 95 % porous and consisted of a pore size gradient bone compartment and periodontal compartment made of fibre-guiding channels with micro-architectural features ranging from 100 to 60 µm aimed to direct PDL fibre alignment and attachment. In vitro evaluations over 3 and 7 days demonstrated a marked improvement in collagen fibre orientation (over 60 % fully aligned) for scaffolds with micro-architecture ≤100 µm. The biphasic scaffolds were placed on a dentine slice and implanted ectopically, and this demonstrated that all micro-channels groups facilitated oblique and perpendicular alignment and attachment on the dentine with a mean nuclei angle and mean collagen fibre angle of approximately 60° resembling the native periodontal ligament attachment. A further in vivo testing using a surgically created rodent periodontal model highlighted the 80 µm micro-channel group's effectiveness, showing a significant increase in oblique PDL fibre attachment (72 %) and periodontal regeneration (56 %) when compared to all other groups onto the tooth root compared to control groups. Further to this, immunohistochemistry demonstrated the presence of periostin in the newly formed ligament indicating that functional regeneration occurred These findings suggest that scaffold micro-architectures of 100 µm or below can play a crucial role in directing periodontal tissue regeneration, potentially addressing a critical gap in periodontal therapy. Statement of significancePeriodontal regeneration remains a significant clinical challenge. Essential to restoring dental health and function is the proper attachment of the periodontal ligament, which is functionally oriented, to regenerated bone and cementum. Our research presents an innovative biphasic scaffold, utilizing Melt Electrowriting to systematically guide tissue growth. Distinct from existing methods, our scaffold is highly porous, adaptable, and precisely guides periodontal ligament fibre attachment to the opposing tooth root and alveolar bone interfaces, a critical step for achieving periodontal functional regeneration. Our findings not only bridge a significant gap in biomaterial driven tissue guidance but also promise more predictable outcomes for patients, marking a transformative advancement in the field.

Prognostic significance of connective tissue growth factor expression in stromal cells in patients with diffuse‑type gastric cancer.

Connective tissue growth factor (CTGF) is a target gene of the Hippo signaling pathway. Its differential role in the histological types of gastric cancer (GC) remains unknown; therefore, the present study aimed to confirm the clinical significance of CTGF expression in cancer and stromal cells in patients with GC depending on the histological type. The present study enrolled 589 patients with GC. Immunohistochemistry was used to analyze CTGF expression in cancer and stromal cells. CTGF mRNA expression data and the corresponding clinical information of GC samples were collected from The Cancer Genome Atlas (TCGA) database. Subsequently, the associations between CTGF expression and several clinicopathological factors were investigated. In the present study, CTGF expression was mainly observed in the cytoplasm of cancer and stromal cells. CTGF expression in stromal cells was significantly associated with CTGF expression in cancer cells (P<0.001). CTGF positivity in stromal cells was also significantly associated with intestinal type, non-scirrhous type, tumor depth (T1-2), lymph node metastasis (negative), lymphatic invasion (negative) and tumor size (<5 cm). Low CTGF expression in stromal cells was independently associated with worse overall survival (OS). Furthermore, the OS of patients with low CTGF expression in stromal cells, especially in patients with diffuse-type GC, was significantly worse than patients with high CTGF expression (P=0.022). This trend was similar to that revealed by TCGA data analysis. In conclusion, low CTGF expression was associated with a significantly worse OS in patients with diffuse-type GC. These data indicated that CTGF, and its control by the Hippo pathway, may be considered potential treatment targets in diffuse-type GC.

Enhancing bone tissue engineering using iron nanoparticles and magnetic fields: A focus on cytomechanics and angiogenesis in the chicken egg chorioallantoic membrane model.

To evaluate the potential of iron nanoparticles (FeNPs) in conjunction with magnetic fields (MFs) to enhance osteoblast cytomechanics, promote cell homing, bone development activity, and antibacterial capabilities, and to assess their in vivo angiogenic viability using the chicken egg chorioallantoic membrane (CAM) model. Experimental study conducted in a laboratory setting to investigate the effects of FeNPs and MFs on osteoblast cells and angiogenesis using a custom titanium (Ti) substrate coated with FeNPs. A custom titanium (Ti) was coated with FeNPs. Evaluations were conducted to analyze the antibacterial properties, cell adhesion, durability, physical characteristics, and nanoparticle absorption associated with FeNPs. Cell physical characteristics were assessed using protein markers, and microscopy, CAM model, was used to quantify blood vessel formation and morphology to assess the FeNP-coated Ti's angiogenic potential. This in vivo study provided critical insights into tissue response and regenerative properties for biomedical applications. Statistical analysis was performed using appropriate tests to compare experimental groups and controls. Significance was determined at P < 0.05. FeNPs and MFs notably improved osteoblast cell mechanical properties facilitated the growth and formation of new blood vessels and bone tissue and promoted cell migration to targeted sites. In the group treated with FeNPs and exposed to MFs, there was a significant increase in vessel percentage area (76.03%) compared to control groups (58.11%), along with enhanced mineralization and robust antibacterial effects (P < 0.05). The study highlights the promising potential of FeNPs in fostering the growth of new blood vessels, promoting the formation of bone tissue, and facilitating targeted cell migration. These findings underscore the importance of further investigating the mechanical traits of FeNPs, as they could significantly advance the development of effective bone tissue engineering techniques, ultimately enhancing clinical outcomes in the field.

#47. Chemotherapy-induced microenvironmental changes promote dormant breast cancer cell growth in the adipose tissue

#47. Chemotherapy-induced microenvironmental changes promote dormant breast cancer cell growth in the adipose tissue

Long-Term Ultrasound Twinkling Detectability and Safety of a Polymethyl Methacrylate Soft Tissue Marker Compared to Conventional Breast Biopsy Markers—A Preclinical Study in a Porcine Model

ObjectiveWe have studied the use of polymethyl methacrylate (PMMA) as an alternative biopsy marker that is readily detectable with ultrasound Doppler twinkling in cases of in vitro, ex vivo, or limited duration in vivo settings. This study investigates the long-term safety and ultrasound Doppler twinkling detectability of a PMMA breast biopsy marker following local perturbations and different dwell times in a 6-mo animal experiment. MethodsThis study, which was approved by our Institutional Animal Care and Use Committee, involved three pigs and utilized various markers, including PMMA (Zimmer Biomet), 3D-printed, and Tumark Q markers. Markers were implanted at different times for each pig. Mesh material or ethanol was used to induce a local inflammatory reaction near certain markers. A semiquantitative twinkling score assessed twinkling for actionable localization during monthly ultrasounds. At the primary endpoint, ultrasound-guided localization of lymph nodes with detectable markers was performed. Following surgical resection of the localized nodes, histomorphometric analysis was conducted to evaluate for tissue ingrowth and the formation of a tissue rind around the markers. ResultsNo adverse events occurred. Twinkling scores of all markers for all three pigs decreased gradually over time. The Q marker exhibited the highest mean twinkling score followed by the PMMA marker, PMMA with mesh, and Q with ethanol. The 3D-printed marker with mesh and PMMA with ethanol had the lowest scores. All wire-localized lymph nodes were successfully resected. Despite varying percentages of tissue rind around the markers and a significant reduction in overall twinkling (p < 0.001) over time, mean PMMA twinkling scores remained clinically actionable at 6 and 5 mo using a General Electric C1-6 probe and 9L-probe, respectively. ConclusionsIn this porcine model, the PMMA marker demonstrates an acceptable safety profile. Clinically actionable twinkling aids PMMA marker detection even after 6 mo of dwell time in porcine lymph nodes. The Q marker maintained the greatest twinkling over time compared to all the other markers studied.

Molecular Engineering of D‐π‐A Conjugate with N‐Heterocycle Purine for Enhanced ROS Generation and Photodynamic Therapy

AbstractThe efficient generation of reactive oxygen species (ROS) is crucial for the photodynamic therapy (PDT) effect. The D‐π‐A molecular engineering strategy can effectively separate the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) distribution to achieve a smaller energy gap thereby facilitating ROS generation of photosensitizers (PSs). Incorporating heterocycles as π‐bridges can not only extend the conjugation system with improving the degree of π‐delocalization but also effectively accelerate the intersystem crossing process. Herein, a N‐heterocycle purine is innovatively integrated into the D‐π‐A structure as a π‐bridge, which significantly enhances the photodynamic performance by achieving high levels of Type I and Type II ROS generation. The most potent TPM‐QN2 is obtained by modulating the electron‐withdrawing ability of the acceptor (quinolinium), with a 1O2 yield of 9.32, which is the highest yield reported to date. Furthermore, these purine‐based PSs exhibit excellent capabilities in promoting cell photodynamic ablation and inhibiting tumor tissue growth. This novel approach of introducing natural heterocycles provides a promising avenue for developing high‐performance PSs and promoting tumor phototherapy.

Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development.

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Sini decoction against renal fibrosis.

To investigate the mechanism by which Sini decoction (, SND) improves renal fibrosis (Rf) in rats based on transforming growth factor β1/Smad (TGF-β1/Smad) signaling pathway. Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf. The targets of SND drug components and the targets of Rf were obtained by searching databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP) and GeenCard. The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram. Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway. The Rf rat model was established by unilateral ureteral occlusion (UUO). The expression levels of transforming growth factor, matrix metalloproteinase-9 (MMP-9), matrix metal protease-2 (MMP-2), connective tissue growth factor (CTGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by Masson staining of rat renal tissue, and immunohistochemical methods. The expression levels of Smad3, Smad2, and Smad7 in renal tissue were determined by Western blotting (WB). The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway. A total of 12 drug components of Fuzi (Radix Aconiti Lateralis Preparata), 5 drug components of Ganjiang (Rhizoma Zingiber), and 9 drug components of Gancao (Radix Glycy et Rhizoma) were obtained from the database search, and 207 shared targets were found. A total of 1063 Rf targets were found in the database search. According to the Venn diagram, in total, 96 intersection targets were found in two database searches. The metabolic pathways involved included TGF-β signaling pathway, phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling (PI3K/Akt) pathway, and hypoxia-inducible factor-1 (HIF-1) signaling pathway. Masson staining analysis showed that compared with the model group, the renal interstitial collagen deposition levels in the SSN and SND groups were significantly lower (P < 0.05). Immunohistochemical analysis, compared with the control group, the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the model group were significantly decreased (P < 0.05, P < 0.01), and the positive cell area expression levels of CTGF and TGF-β1 were significantly increased (P < 0.01). Compared with the model group, the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the SSN and SND groups were significantly increased (P < 0.05, P < 0.01), and the positive cell area expression levels of CTGF and TGF-β1 in the kidney tissue were significantly decreased (P < 0.05, P < 0.01). WB results showed that the SSN group and the SND group could reduce the expression of Smad2 and Smad3 (P < 0.05) and increase the expression of Smad7 (P < 0.05).

Medical Image Segmentation for Brain Tumor Detection Using U-NET

Abstract: Brain tumors encompass a wide variety of growths that can occur in the cranial cavity. These tumors can be benign or malignant, and early identification is important for suitable treatment. MRI is a non-invasive imaging method that provides detailed anatomical information and is useful in diagnosing and monitoring brain tumors. However, identifying tumors from complex MRI data remains a difficult and challenging task. This project uses image segmentation techniques to identify and identify tumors on MRI scans. The technology is works on the principles of deep learning, an intelligence process that enables computers to learn and recognize patterns in large data sets. This learning process helps doctors make informed decisions by distinguishing between healthy brain tissue and tumor growth. The unique design of the U-Net architecture, characterized by a U-shaped pattern with compactness and detail, makes it possible to capture complex patterns and fine details in medical images. Using different data from many brain MRI scans, the U-Net algorithm was trained to depict tumor regions with pixel-level accuracy.

Adverse events associated with Vibrant Soundbridge: A MAUDE study

ObjectiveTo summarize adverse events and their root causes reported to the United States Food and Drug Administration (FDA) on Vibrant Soundbridge (VSB) hearing device (Med-El, Innsbruck, Austria), an active middle ear implant for patients with moderate to severe hearing loss. Materials and methodsThe FDA's Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports of VSB adverse events from January 1, 2012, to July 27, 2022. ResultsSix hundred sixty-three total medical device reports were identified, from which 913 adverse events were extracted. Of these, 498 (54.5 %) were adverse events to patients (AEPs), while 415 (45.5 %) were device malfunctions (DMs). The most common AEPs were hearing performance issues 428 (85.9 %). The most common DMs were compromised conductive link 125 (30.1 %). Root causes identified for DMs were iatrogenic 85 (58.6 %), patient-related 28 (19.3 %), and trauma and external causes 32 (22.1 %). The most common iatrogenic root cause 12 (14.1 %) involved damage to the conductive link during revision surgery. The most common patient-related causes of DMs were excessive middle ear tissue growth 16 (57 %), and abrupt body movements 5 (28.6 %). The most common external cause of DM was cleaning of the ear canal or mastoid cavity 20 (62.5 %). ConclusionsDespite its well-known limitations, the MAUDE database provides valuable information on possible complications of VSB as it relates to device malfunction or adverse events for patients. Implementation of standardized reports with relevant and well-defined categories could certainly allow for a more meaningful analysis.

Insight into Insulin-like Growth Factor-1 Receptor (IGF-1R) gene mutations: Implications for growth disorders and treatment: A review of the literature and case report

Background: Insulin-like Growth Factor -1 Receptor (IGF-1R) and its ligand, IGF-1, are crucial for human tissue growth and development. Mutations in IGF-1R and, to a lesser extent, IGF-1 genes lead to diverse growth disorders, characterized by intrauterine growth retardation and postnatal growth challenges. Case report: We present a case of a 6-year-old girl with speech and mild cognitive delays, exhibiting normal motor skills, no neurological issues, and standard vital signs. Her growth parameters indicated significant retardation, with a height standard deviation score (Ht-SDS) of -2 and an IGF-1 level of +1.8 SDS, normal thyroid function and delayed bone age. Genetic analysis identified a 3335 mbp interstitial loss in 15q26.1, encompassing the IGF-1R gene, critical for growth and development. Literature review: Analysis of 34 papers provided insight into the genetic complexities of IGF-1R and IGF-1 mutations. Studies ranged from familial cases to cohort studies, uncovering mutations including missense mutations, deletions, and copy number variations (CNVs), each associated with unique growth disorder phenotypes. Advances in diagnostic techniques like multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing (WES) have been pivotal in identifying these mutations, facilitating more targeted management approaches. Conclusions: This case and review of literature underscore the importance of an integrated genetic, endocrine, and developmental approach in managing growth hormone deficiency (GHD) and IGF-1 resistance. The variability in growth disorders and response to therapy highlights the need for personalized treatment plans, informed by genetic insights, to optimize outcomes for patients with these complex conditions.

Advancements and Challenges in Hydrogel Engineering for Regenerative Medicine.

This manuscript covers the latest advancements and persisting challenges in the domain of tissue engineering, with a focus on the development and engineering of hydrogel scaffolds. It highlights the critical role of these scaffolds in emulating the native tissue environment, thereby providing a supportive matrix for cell growth, tissue integration, and reducing adverse reactions. Despite significant progress, this manuscript emphasizes the ongoing struggle to achieve an optimal balance between biocompatibility, biodegradability, and mechanical stability, crucial for clinical success. It also explores the integration of cutting-edge technologies like 3D bioprinting and biofabrication in constructing complex tissue structures, alongside innovative materials and techniques aimed at enhancing tissue growth and functionality. Through a detailed examination of these efforts, the manuscript sheds light on the potential of hydrogels in advancing regenerative medicine and the necessity for multidisciplinary collaboration to navigate the challenges ahead.

3D cotton-type anisotropic biomimetic scaffold with low fiber motion electrospun via a sharply inclined array collector for induced osteogenesis

Electrospinning is an effective method to fabricate fibrous scaffolds that mimic the ECM of bone tissue on a nano- to macro-scale. However, a limitation of electrospun fibrous scaffolds for bone tissue engineering is the structure formed by densely compacted fibers, which significantly impedes cell infiltration and tissue ingrowth. To address this problem, several researchers have developed numerous techniques for fabricating 3D fibrous scaffolds with customized topography and pore size. Despite the success in developing various 3D electrospun scaffolds based on fiber repulsion, the lack of contact points between fibers in those scaffolds has been shown to hinder cell attachment, migration, proliferation, and differentiation due to excessive movement of the fibers. In this article, we introduce a Dianthus caryophyllus-inspired scaffold fabricated using SIAC-PE, a modified collector under specific viscosity conditions of PCL/LA solution. The developed scaffold mimicking the structural similarities of the nature-inspired design presented enhanced cell proliferation, infiltration, and increased expression of bone-related factors by reducing fiber movements, presenting high space interconnection, high porosity, and controlled fiber topography.

Alteration of mechanical stresses in the murine brain by age and hemorrhagic stroke.

Residual mechanical stresses, also known as solid stresses, emerge during rapid differential growth or remodeling of tissues, as observed in morphogenesis and tumor growth. While residual stresses typically dissipate in most healthy adult organs, as the growth rate decreases, high residual stresses have been reported in mature, healthy brains. However, the origins and consequences of residual mechanical stresses in the brain across health, aging, and disease remain poorly understood. Here, we utilized and validated a previously developed method to map residual mechanical stresses in the brains of mice across three age groups: 5-7 days, 8-12 weeks, and 22 months. We found that residual solid stress rapidly increases from 5-7 days to 8-12 weeks and remains high in mature 22 months mice brains. Three-dimensional mapping revealed unevenly distributed residual stresses from the anterior to posterior coronal brain sections. Since the brain is rich in negatively charged hyaluronic acid, we evaluated the contribution of charged extracellular matrix (ECM) constituents in maintaining solid stress levels. We found that lower ionic strength leads to elevated solid stresses, consistent with its unshielding effect and the subsequent expansion of charged ECM components. Lastly, we demonstrated that hemorrhagic stroke, accompanied by loss of cellular density, resulted in decreased residual stress in the murine brain. Our findings contribute to a better understanding of spatiotemporal alterations of residual solid stresses in healthy and diseased brains, a crucial step toward uncovering the biological and immunological consequences of this understudied mechanical phenotype in the brain.

Effects of Cochlear Implantation and Steroids on the Aging Guinea Pig Cochlea.

The objective was to determine the effects of older age on hearing preservation after cochlear implantation (CI), and whether steroids improve hearing preservation in older animals. We hypothesized greater hearing preservation would be observed in (1) young animals compared to older animals and (2) older animals receiving steroids compared to no steroids. The secondary objective was to assess levels of fibrosis utilizing optical coherence tomography (OCT). Experimental Animal Study. Laboratory. Three groups of guinea pigs: young (YCI; 8.5 ± 0.5 weeks; n = 10), old (OCI; 19.1 ± 1.0 months; n = 9) and old + steroids (OCI+S; 19.1 ± 1.0 months; n = 9) underwent CI. The OCI+S group received a steroid taper over 7 days starting 2 days before surgery to 4 days after. Auditory brainstem response (ABR) measurements were performed preoperatively and postoperatively. OCT imaging was performed to assess cochleae for extent of fibrotic tissue growth in the scala tympani. The YCI group had significantly better hearing preservation as measured by smaller increases in ABR thresholds [mean shift: 2.79 ± 0.66] compared to the OCI group [mean shift = 12.44 ± 5.6]. The OCI+S group had significantly better hearing preservation [2.66 ± 1.50] compared to the OCI group. No significant differences was seen in fibrosis across groups. Young animals and older animals that received steroids had better hearing after CI than older animals not given steroids, but hearing preservation was not correlated with the level of fibrosis assessed using OCT. This work is the first to investigate differences in hearing preservation by age in an animal model, and supports the protective effects of steroids on hearing preservation in older individuals.

Negative Pressure Wound Therapy: Challenges, Novel Techniques, and Future Perspectives.

Significance: Negative pressure wound therapy (NPWT) has been in practice for decades, proving its utility in many applications, ranging from acutely infected wounds to complex combat wounds and skin grafting. It has been routinely demonstrated that NPWT has superior wound healing outcomes compared with previous standard-of-care therapies. However, the technique involves some challenges related to each of the components that comprise the therapy. The purpose of this article is to highlight the challenges, introduce the recent advancements, and discuss about the future directions in NPWT systems. Recent Advances: New techniques and materials have been developed to improve the currently used NPWT systems with promising results when utilized with appropriate indications. Many advancements have been introduced in modes of negative pressure delivery, pumps, interface dressings, adhesive dressings, and tubing technology. Critical Issues: An optimal NPWT system would avoid the common problems such as failure to deliver negative pressure due to loss of an airtight seal or tissue ingrowth into the interface dressing causing painful dressing changes and bleeding. Other challenges include infection control and patient pain and discomfort that may contribute to noncompliance. Future Directions: Many studies have been performed to evaluate the optimal combination of settings and components in various wounds; however, there is still no clear "best" answer for many specific patient-wound scenarios. Novel and emerging tissue engineering and regenerative medicine approaches could potentially be utilized in the future NPWT systems and thus, this review will discuss some novel ideas for future considerations.

Haemodynamics of stent-mounted neural interfaces in tapered and deformed blood vessels

The endovascular neural interface provides an appealing minimally invasive alternative to invasive brain electrodes for recording and stimulation. However, stents placed in blood vessels have long been known to affect blood flow (haemodynamics) and lead to neointimal growth within the blood vessel. Both the stent elements (struts and electrodes) and blood vessel wall geometries can affect the mechanical environment on the blood vessel wall, which could lead to unfavourable vascular remodelling after stent placement. With increasing applications of stents and stent-like neural interfaces in venous blood vessels in the brain, it is necessary to understand how stents affect blood flow and tissue growth in veins. We explored the haemodynamics of a stent-mounted neural interface in a blood vessel model. Results indicated that blood vessel deformation and tapering caused a substantial change to the lumen geometry and the haemodynamics. The neointimal proliferation was evaluated in sheep implanted with an endovascular neural interface. Analysis showed a negative correlation with the mean Wall Shear Stress pattern. The results presented here indicate that the optimal stent oversizing ratio must be considered to minimise the haemodynamic impact of stenting.

Granular Hydrogels Improve Myogenic Invasion and Repair after Volumetric Muscle Loss.

Skeletal muscle injuries including volumetric muscle loss (VML) lead to excessive tissue scarring and permanent functional disability. Despite its high prevalence, there is currently no effective treatment for VML. Bioengineering interventions such as biomaterials that fill the VML defect to support cell and tissue growth are a promising therapeutic strategy. However, traditional biomaterials developed for this purpose lack the pore features needed to support cell infiltration. The present study investigates for the first time, the impact of granular hydrogels on muscle repair - hypothesizing that their flowability will permit conformable filling of the defect site and their inherent porosity will support the invasion of native myogenic cells, leading to effective muscle repair. Small and large microparticle fragments are prepared from photocurable hyaluronic acid polymer via extrusion fragmentation and facile size sorting. In assembled granular hydrogels, particle size and degree of packing significantly influence pore features, rheological behavior, and injectability. Using a mouse model of VML, it is demonstrated that, in contrast to bulk hydrogels, granular hydrogels support early-stage (satellite cell invasion) and late-stage (myofiber regeneration) muscle repair processes. Together, these results highlight the promising potential of injectable and porous granular hydrogels in supporting endogenous repair after severe muscle injury.

Ianus Bifrons: The Two Faces of Metformin.

The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open?

Malnutrition, dysfunction of the gastrointestinal tract and sarcopenia - features of combined pathology

One of the risk factors for the development of sarcopenia is malnutrition. Impairment of the energy value of the diet, the balance of proteins, fats and carbohydrates, a decrease in the protein-amino acid component of the nutritional diet - all this can lead to the development of sarcopenia. The intestinal microflora plays an important role in the process of growth and development of muscle tissue, in preventing its degradation with age. Fatty hepatosis and cirrhosis of the liver can also cause the development of sarcopenia. The problem is urgent and modern, and needs to be studied, which is what this literature review is dedicated to.