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Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dustfree granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture, compressibility, etc. together with physical and chemical stability of the drug. Granulation process can be divided into two types: wet granulation that utilize a liquid in the process and dry granulation that requires no liquid. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. Among currently available technologies, spray drying, roller compaction, high shear mixing, and fluid bed granulation are worth of note. Like any other scientific field, pharmaceutical granulation technology also continues to change, and arrival of novel and innovative technologies are inevitable. This review focuses on the recent progress in the granulation techniques and technologies such as pneumatic dry granulation, reverse wet granulation, steam granulation, moisture-activated dry granulation, thermal adhesion granulation, freeze granulation, and foamed binder or foam granulation. This review gives an overview of these with a short description about each development along with its significance and limitations.

Our study aims to investigate the effect of negative pressure wound therapy (NPWT) on microRNA-155 (miR-155) in the granulation tissue of patients suffering from diabetic foot ulcers (DFUs) and its correlation with wound healing. A total of sixty patients diagnosed with DFUs were randomly assigned to either the NPWT group ( n  = 40) or the Non-NPWT group ( n  = 20) in a 2:1 ratio. After debridement, the NPWT group received NPWT treatment for one week, while the Non-NPWT group underwent routine dressing therapy. The expression of miR-155 in DFU granulation tissues was evaluated by qRT-PCR before and after treatment for one week. Following termination, wound healing rates were assessed in the NPWT group, and the correlation between variations in miR-155 expression (ΔmiR-155) and wound healing was analyzed pre and post NPWT treatment. In vitro experiments were conducted to investigate the effects of negative pressure on variations of miR-155 expression, as well as proliferation, migration, and apoptosis in normal human dermal fibroblasts (NHDFs). The NPWT group showed a decrease in miR-155 expression in wound granulation tissue compared with pre-treatment [4.12 (1.22, 14.85) vs. 6.83 (2.15, 15.72), P  < 0.05]. Conversely, there was no statistically significant difference in miR-155 expression in wound granulation tissue between pre-treatment and post-treatment in the Non-NPWT group ( P  > 0.05). However, analysis revealed a positive correlation between ΔmiR-155 and wound healing rate after 4 weeks in the NPWT group (χ 2  = 4.829, P  = 0.028). The in vitro experiments showed a significant decrease in miR-155 expression in NHDFs under negative pressure measured at -125 mmHg ( P  < 0.05). This reduction in miR-155 expression, in turn, enhanced the proliferation and migration ability while decreasing the apoptosis rate of NHDFs by targeting the upregulation of fibroblast growth factor 7 (FGF7) gene expression ( P  < 0.05). It is concluded that NPWT promotes DFU healing by reducing the expression of miR-155 in granulation tissue and the efficacy of NPWT correlated with altered miR-155 expression in wound tissue.

Background Granulation tissue formation is a frequent complication following airway implant procedures such as endobronchial valve (EBV) therapy in patients with chronic obstructive pulmonary disease (COPD). This hyperplastic response can impair implant function and clinical outcomes, yet the underlying immunological mechanisms remain poorly understood. Methods In a cohort of EBV patients ( n  = 147), we developed an optical scaling and scoring system to classify the severity of granulation tissue in relation to clinical outcomes. Based on this system, we prospectively collected endobronchial biopsies from EBV ( n  = 41) and stent patients ( n  = 11) for immune and structural profiling across different severity grades. Granulation tissue was analysed by histology, immunofluorescence, and flow cytometry. Results Using the optical scoring system, almost 75% of EBV patients developed hyperplastic granulation tissue (34.7% moderate, 38.8% severe). In many moderate to severe cases, valve dysfunction, dislocation, and the need for revision was observed. Increasing severity of granulation tissue was associated with profound extracellular matrix (ECM) disruption and increased immune cell infiltration. Immunophenotyping revealed elevated neutrophils and regulatory T cells (Tregs) with a central memory phenotype. Macrophages in patients with severe granulation tissue formation showed a shift toward a CD163 + M2-like polarisation. Structural analyses demonstrated a loss of epithelial integrity and an upregulation of ECM remodelling markers, fibronectin, and tenascin C. Conclusion This study provides the first systematic immune-morphological classification of airway granulation tissue following EBV therapy. Our findings revealed distinct immune and ECM signatures associated with clinical complications identify potential mechanisms and therapeutic targets, particularly relevant for COPD patients in whom current anti-inflammatory strategies are insufficient. Graphical abstract Overview of the study design and main findings on the immunological and structural characterisation of granulation tissue following endobronchial valve (EBV) or stent implantation. Granulation tissue was obtained by forceps biopsy during bronchoscopy. Scoring was performed according to severity, followed by histological and immunofluorescence analysis for immune cell infiltration, immunophenotyping by flow cytometry, and assessment of extracellular matrix (ECM) remodelling. Increased granulation grade was associated with clinical complications including EBV dislocation, dysfunction, and need for revision procedures. Key immune cell types [neutrophils, type 2 T helper (Th2) cells, regulatory T cells (Treg), central memory cells (CM), CD16high natural killer cells (NK), CD163 + macrophages], goblet cells, fibroblasts, endothelial cells (endoglin, ICAM), and ECM components (β-Catenin, fibronectin, collagen IV, tenascin C, pan-laminin).

Aim This study aims to compare the clinical and radiographic outcomes after complete versus incomplete removal of granulation tissue (GT) during modified minimally invasive surgical technique (M-MIST) for management of periodontitis patients with deep pockets associated with infra-bony defects. Methodology Ten patients with a total of 14 deep non-resolving pockets (≥ 5 mm) associated with a vertical infra-bony defect were recruited for this study. They were randomized into 2 groups; a test group with incomplete removal of GT and a control group with complete removal of GT. Clinical parameters of clinical attachment level (CAL), residual probing depth (rPD) and buccal recession (Rec.) were recorded every 3 months. Radiographic periapicals were taken at baseline, 6 and 9 months. The significance level was set to 0.05. Results None of the results showed statistical significance between the 2 groups ( p  > 0.05). The test group showed less CAL gain (2 ± 0.87 mm, p  = 0.062), more reduction in rPD (3.1 ± 0.96 mm, p  = 0.017) and more recession (0.857 ± 0.26 mm, p  = 0.017) than control group CAL gain (2.4 ± 0.58 mm, p  = 0.009), rPD reduction (2.9 ± 0.3 mm, p  = 0.001) and recession (0.5 ± 0.34 mm, p  = 0.203) respectively. Control group had linear reduction in depth defect (DD) (0.68 ± 0.287, p  = 0.064) compared to an increase in DD in test group (-0.59 ± 0.5, p  = 0.914). Conclusions No statistical significance were observed in healing parameters between complete removal of GT in M-MIST and incomplete (partial) removal of GT of deep pockets with infra-bony defects both clinically and radiographically. Further studies with larger samples are needed to confirm the results.

We present an updated version of the GRanulation And Spectrum Simulator (GRASS) which now uses an expanded library of 22 solar lines to empirically model time-resolved spectral variations arising from solar granulation. We show that our synthesis model accurately reproduces disk-integrated solar line profiles and bisectors, and we quantify the intrinsic granulation-driven radial-velocity (RV) variability for each of the 22 lines studied. We show that summary statistics of bisector shape (e.g., bisector inverse slope) are strongly correlated with the measured anomalous, variability-driven RV at high pixel signal-to-noise ratio SNR and spectral resolution. Further, the strength of the correlations varies both line by line and with the summary statistic used. These correlations disappear for individual lines at the typical spectral resolutions and SNRs achieved by current extremely precise radial velocity spectrographs; so we use simulations from GRASS to demonstrate that they can, in principle, be recovered by selectively binning lines that are similarly affected by granulation. In the best-case scenario (high SNR and large number of binned lines), we find that a ≲30% reduction in the granulation-induced root mean square RV can be achieved, but that the achievable reduction in variability is most strongly limited by the spectral resolution of the observing instrument. Based on our simulations, we predict that existing ultra-high-resolution spectrographs, namely, ESPRESSO and PEPSI, should be able to resolve convective variability in other, bright stars.

This study explored the clinical effectiveness of antibiotic-loaded bone cement on primary treatment of diabetic foot infection. This is a randomized controlled study, including thirty-six patients with diabetic foot ulcer complicated by osteomyelitis who had undergone treatment between May 2018 and December 2019. Patients were randomly divided into control group (group A) and study group (group B). Patients in the intervention group received antibiotic-loaded bone cement repair as primary treatment, while patients in the control group received conventional vacuum sealing draining treatment. Clinical endpoints were assessed and compared between the two groups, including wound healing time, wound bacterial conversion, NRS pain score, number of wound dressing changes, and average hospitalization time. All patients were followed up for a period of 12 months after discharge. Results show that compared with the control group, patients in the study group had significant difference in the number of patients for baseline pathogens eradication, short NRS pain score, hospital length of stay and cost, wound surface reduction, healing time, low rate of complications, and infection recurrence. Based on the findings, we conclude that antibiotic-loaded bone cement can be used for treatment of wound in patient with diabetic foot infection. It can help to control wound infections, shorten hospital length of stay, reduce medical cost, and relieve both doctors’ and patients’ burden. The application of antibiotic-loaded bone cement is suitable for diabetic wound with soft tissue infection or osteomyelitis.

Stellar granulation is a source of radial-velocity (RV) jitter of 1 m s−1 on Sun-like stars, limiting the detection of Earth analogs. One way to move beyond this limit is to use line-weighting schemes to mitigate granulation-driven RV variability in a spectral-type-dependent manner. A physics-based granulation-sensitivity diagnostic is essential. Here, we use a line-by-line sensitivity measure from 3D magnetoconvection simulations that quantifies how strongly each spectral line’s Doppler shift and strength respond to convective velocity and thermodynamic fluctuations. Extending our previous solar analysis, which used the spatial variability of line profiles across a single granulation snapshot as a computationally efficient proxy for temporal variability, we test the transferability of this diagnostic to cooler stars and characterize how line sensitivity varies with spectral type. We synthesize high-resolution spectra with the Merged Parallelised Simplified ATLAS code from 3D time-dependent MURaM simulations representative of the Sun and late-G and K dwarfs, focusing on neutral and singly ionized iron lines spanning a wide range of excitation potentials and strengths. As Teff decreases, convective velocities weaken, and the ionization balance shifts, producing a clearer separation between line families: Fe i lines show lower velocity sensitivity and smaller fractional strength variability, whereas Fe ii lines show the opposite. Using cumulative contribution functions, we further relate spectroscopic velocity jitter to characteristic line-formation temperature. The diagnostic continues to separate robust and sensitive lines in late-G and K dwarfs, enabling spectral-type-aware cross-correlation masks and line-by-line weights. Solar-optimized line selections are not generally portable to cooler stars, especially when based on equivalent-width stability rather than velocity sensitivity.

Platelet‐Derived Growth Factors (PDGFs) and Transforming Growth Factor β (TGFβ) are pivotal in orchestrating the complex wound healing process, particularly in granulation tissue formation. This review aims to comprehensively examine the roles of PDGF alongisde TGFβ in granulation tissue formation and their implications for abnormal wound healing. PDGFs, as homodimeric or heterodimeric combinations, such that PDGF‐AA, PDGF‐AB and PDGF‐BB stimulate fibroblast proliferation and extracellular matrix synthesis, which is crucial for tissue repair. TGFβ, with its three isoforms, influences granulation tissue through diverse functions, with TGFβ‐1 pivotal in fibrosis formation. Understanding their signalling pathways, notably PDGF's engagement with PDGF receptors and subsequent activation of cellular pathways, illuminates their roles in wound healing cascades. Excessive granulation, a complication of abnormal wound healing, involves dysregulated PDGF and TGFβ activity, leading to hypertrophic scar formation. Clinical management, particularly in ophthalmology, addresses excessive granulation's impact on procedures like endo‐dacryocystorhinostomy. Strategies employing steroid agents and Mitomycin‐C aim to mitigate ostium granulation. The potential use of PDGF receptor blockers, such as olaratumab, warrants further investigation for managing excessive granulation. In conclusion, PDGF and TGFβ emerge as critical regulators in granulation tissue formation, underscoring their significance in wound healing processes and offering avenues for therapeutic intervention.

Exuberant granulation tissue (EGT) is a second intention wound healing disorder. It commonly occurs in the distal limb of horses. EGT causes significant increase in the duration and cost of treatment, potentially leading to the decision not to pursue treatment and euthanize the patient. The underlying pathomechanisms of this fibroproliferative disorder remain unclear, particularly in terms of collagen composition and the association between myofibroblasts and blood vessels. This study investigated the collagen composition in naturally occurring EGT following trimming in 19 horses (EGT group). In both the superficial and deep wound beds of EGT-affected horses, the collagen distribution was assessed and compared to control wounds (n = 6 horses, control group, punch biopsies) using histology. Immunofluorescence was performed to colocalize activated alpha smooth muscle actin-positive myofibroblasts in EGT as well as angiogenic markers. Our histological findings showed significantly higher amounts of immature collagen (type III) in the superficial and deep regions of EGT compared to the controls while the total amount of collagen in both groups did not differ significantly. In EGT, occluded microvessels and endothelial cell hypertrophy were present in the deep layer and myofibroblasts were ubiquitously found in the whole wound bed. Markers for intermediate filaments were reduced in the superficial region. In conclusion, collagen composition in EGT differed significantly from control wounds, indicating tissue immaturity. Consequently, promoting tissue maturation towards a more mature ECM composition could serve as a valuable target for future therapeutic interventions enabling better regeneration.

Owing to recent advances in radial-velocity instrumentation and observation techniques, the detection of Earth-mass planets around Sun-like stars may soon be primarily limited by intrinsic stellar variability. Several processes contribute to this variability, including starspots, pulsations, and granulation. Although many previous studies have focused on techniques to mitigate signals from pulsations and other types of magnetic activity, granulation noise has to date only been partially addressed by empirically motivated observation strategies and magnetohydrodynamic simulations. To address this deficit, we present the GRanulation And Spectrum Simulator (GRASS), a new tool designed to create time-series synthetic spectra with granulation-driven variability from spatially and temporally resolved observations of solar absorption lines. In this work, we present GRASS, detail its methodology, and validate its model against disk-integrated solar observations. As a first-of-its-kind empirical model for spectral variability due to granulation in a star with perfectly known center-of-mass radial-velocity behavior, GRASS is an important tool for testing new methods of disentangling granular line-shape changes from true Doppler shifts.