Photo-expansion microscopy enables super-resolution imaging of cells embedded in 3D hydrogels.

Hydrogels are extensively used as tunable, biomimetic three-dimensional cell culture matrices, but optically deep, high-resolution images are often difficult to obtain, limiting nanoscale quantification of cell-matrix interactions and outside-in signalling. Here we present photopolymerized hydrogels for expansion microscopy that enable optical clearance and tunable ×4.6-6.7 homogeneous expansion of not only monolayer cell cultures and tissue sections, but cells embedded within hydrogels. The photopolymerized hydrogels for expansion microscopy formulation relies on a rapid photoinitiated thiol/acrylate mixed-mode polymerization that is not inhibited by oxygen and decouples monomer diffusion from polymerization, which is particularly beneficial when expanding cells embedded within hydrogels. Using this technology, we visualize human mesenchymal stem cells and their interactions with nascently deposited proteins at <120 nm resolution when cultured in proteolytically degradable synthetic polyethylene glycol hydrogels. Results support the notion that focal adhesion maturation requires cellular fibronectin deposition; nuclear deformation precedes cellular spreading; and human mesenchymal stem cells display cell-surface metalloproteinases for matrix remodelling.

Single-Step Extrusion Process for Formulation Development of Self-Emulsifying Granules for Oral Delivery of a BCS Class IV Drug.

This study aimed to develop and optimize formulations containinga BCS Class IV drug by improving its solubility and permeability. Herein development of self-emulsifying solid lipid matrices was investigated as carrier systems for a BCS Class IV model drug. Self-emulsifying drug delivery systems (SEDDS) have been extensively investigated for formulating drugs with poor water solubility. However, manufacturing SEDDS is challenging. These systems usually have low drug-loading capacities, and the incorporated drugs tend to recrystallize during storage, which severely impacts the storage stability in vitro and performance in vivo. Moreover, they require greater amounts (>80%) of lipid carriers, cosolvents, surfactants, and other excipients to keep them from recrystallizing. This in turn is again challenging for high-dose drugs as it affects the size of the final drug product (tablets and capsules). Also, the final liquid nature of the formulation affects the handling and processability of the formulation, which poses challenges during the manufacturing and packaging steps. In this work, we have studied the feasibility of a single-step extrusion process to formulate and optimize solid self-emulsifying granules with a relatively higher drug loading of Ritonavir (RTV), a BCS Class IV drug. Further, we have compared the performance of using these granules as the feedstock for direct powder extrusion-based 3D printing as opposed to the use of physical blends. The stability and solubility-permeability advantage of these granules was also evaluated where SEDDS showed about 27 and 20 fold increase in apparent solublity and permeability compared to bulk drug, respectively. Combining the capabilities of HME to form drug-loaded homogeneous granules as a continuous process along with application of direct printing extruiosn (DPE) 3D printing improves the drug delivery prospects for such candidates.

Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections.

Tigecycline (TIG) is a broad-spectrum antibiotic that has been approved for the treatment of a number of complicated infections, including community-acquired bacterial pneumonia. Currently it is available only as an intravenous injection that undergoes rapid chemical degradation and limits the use to in-patient scenarios. The use of TIG as an inhaled dry powder inhaler may offer a promising treatment option for patients with multidrug-resistant respiratory tract infections, such as Stenotrophomonas maltophilia (S. maltophilia). This study explores the feasibility of engineering an inhaled powder formulation of TIG that could administer relevant doses at a wide range of inhalation flow rates while maintaining stability of this labile drug. Using air-jet milling, micronized TIG had excellent aerosolization efficiency, with over 80% of the device emitted dose being within the respirable range. TIG was also readily dispersed using different inhaler devices even when tested at different pressure drops and flow rates. Additionally, micronized TIG was stable for 6 months at 25 °C/60% RH and 40 °C/75% RH. Micronized TIG maintained a low minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of 0.8 µM and >0.5 µM, respectively in S. maltophilia cultures in vitro. These results strongly suggest that the micronization of TIG results in a stable and respirable formulation that can be delivered via the pulmonary route for the treatment of lung infections.

4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture.

Granular synthetic hydrogels are useful bioinks for their compatibility with a variety of chemistries, affording printable, stimuli-responsive scaffolds with programmable structure and function. Additive manufacturing of microscale hydrogels, or microgels, allows for the fabrication of large cellularized constructs with percolating interstitial space, providing a platform for tissue engineering at length scales that are inaccessible by bulk encapsulation where transport of media and other biological factors are limited by scaffold density. Herein, synthetic microgels with varying degrees of degradability are prepared with diameters on the order of hundreds of microns by submerged electrospray and UV photopolymerization. Porous microgel scaffolds are assembled by particle jamming and extrusion printing, and semi-orthogonal chemical cues are utilized to tune the void fraction in printed scaffolds in a logic-gated manner. Scaffolds with different void fractions are easily cellularized post printing and microgels can be directly annealed into cell-laden structures. Finally, high-throughput direct encapsulation of cells within printable microgels is demonstrated, enabling large-scale 3D culture in a macroporous biomaterial. This approach provides unprecedented spatiotemporal control over the properties of printed microporous annealed particle scaffolds for 2.5D and 3D tissue culture.

Retroviral association with ovarian adenocarcinoma in laying hens.

The laying hen has been used as a model for ovarian adenocarcinoma (OAC) in women. Previous work has shown an association between expression of endogenous retroviral proteins and elevated envelope mRNA and occurrence of OAC in humans, but causality has not been demonstrated. The objective of this study was to determine whether there is a similar association between retrovirus presence and OAC in a commercial laying hen flock at the University of Illinois Poultry Research facility with a history of a high OAC prevalence in older hens. Laying hens of three age strata were randomly selected for a cross-sectional study. Blood samples were collected, and serum was tested for antigens of endogenous or exogenous avian leukosis virus (ALV) by ELISA. Birds were humanely euthanized, and spleens, ovaries, and any tissues with gross lesions were sampled. Ovaries and gross lesions were examined histologically and spleens were used for RT-PCR to detect endogenous ALV via ALV-E env mRNA expression. Overall, hens with OAC were 5.2 times more likely to be ALV positive than hens without OAC (95% C.I. 2.06-13.14). Controlled for age, OAC positive hens were 3.6 times more likely to be positive for ALV via antigen-capture ELISA (95% C.I. 1.08-11.96). Endogenous ALV-E in hens may be analogous to human endogenous retroviruses, which have also been associated with OAC in women. Further studies to establish causation are warranted to better understand the potential for laying hens to serve as a laboratory model for viral-induced ovarian tumours in humans. RESEARCH HIGHLIGHTSOAC in hens was associated with age, seropositivity for ALV, and endogenous ALV mRNA expression.Older hens with OAC were more likely to be ALV seropositive by ELISA and ALV-E mRNA-positive.Associations between OAC, age, and endogenous retrovirus expression have been reported in humans.These findings support the use of hens as models for OAC in humans.

Effect of fluorescence quenching model on quinoline derivative with cobalt chloride metal ion using steady state and time resolved spectroscopic methods.

Quinoline derivative, i.e. quinilone yellow with the scientific name [sodium 2-(2,3-dihydro-1,3-dioxo-1H-inden-2-yl)quinoline-6,8-disulphonate] (SQDS) is analysed for fluorescence resonance energy transfer (FRET). Fluorescence quenching mechanism is studied by employing steady state and transient state spectroscopic measurements. Cobalt chloride is used as quencher in the present study. Linearity was observed in Stern-Volmer plots for transient state as well as steady state. This was further attributed to a mechanism of collisional quenching. Efficiency in fluorescence quenching is observed as there is a correlation between quenching constants of both transient and steady state. A significant energy transfer is reported between metal ions and SQDS molecule, according to FRET theory. Characterization results are studied and analysed. Application in the field of non-linear optics are predicted for SQDS. With Kurtz and Perry powder technique, SHG (second harmonic generation) efficiency was measured using Q-switched mode locked Nd:YAG laser emitting 1064 nm the first time with this compound.

NOVEL POXVIRAL INFECTION IN THREE FINCH SPECIES ILLEGALLY IMPORTED INTO TRINIDAD, WEST INDIES, WITH IMPLICATIONS FOR NATIVE BIRDS.

Oryzoborus angolensis (Lesser Seed-Finch), Oryzoborus crassirostris (Large-billed Seed-Finch), and Sporophila intermedia (Grey Seedeater) are finch species native to the Caribbean island of Trinidad. These species are locally trapped and kept for their song, but with declining native populations, enthusiasts have turned to illegally importing birds from the South American mainland. The smuggling of wild birds from South America poses significant disease risks to the native bird species of Trinidad. Herein we describe the first case of poxviral infection in these illegally imported birds in Trinidad and partial genome sequence of the causative agent. Phylogenetic analysis of the 4b core protein sequence indicated that the avian poxvirus identified was most closely related to a 2012 avian pox sequence from Brazil, with 96.2% and 98.1% identity at the nucleotide and amino acid level.

Bis-pyridylethenyl benzene as novel backbone for amyloid-ß binding compounds.

Detection of cerebral ß-amyloid (Aß) by targeted contrast agents is of great interest for in vivo diagnosis of Alzheimer's disease (AD). Partly because of their planar structure several bis-styrylbenzenes have been previously reported as potential Aß imaging agents. However, these compounds are relatively hydrophobic, which likely limits their in vivo potential. Based on their structures, we hypothesized that less hydrophobic bis-pyridylethenylbenzenes may also label amyloid. We synthesized several bis-pyridylethenylbenzenes and tested whether these compounds indeed display improved solubility and lower LogP values, and studied their fluorescent properties and Aß binding characteristics. Bis-pyridylethenylbenzenes showed a clear affinity for Aß plaques on both human and murine AD brain sections. Competitive binding experiments suggested a different binding site than Chrysamine G, a well-known stain for amyloid. With a LogP value between 3 and 5, most bis-pyridylethenylbenzenes were able to enter the brain and label murine amyloid in vivo with the bis(4-pyridylethenyl)benzenes showing the most favorable characteristics. In conclusion, the presented results suggest that bis-pyridylethenylbenzene may serve as a novel backbone for amyloid imaging agents.

Polyfluorinated bis-styrylbenzenes as amyloid-ß plaque binding ligands.

Detection of cerebral ß-amyloid (Aß) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Aß imaging agents. To further explore their potency as (19)F MRI contrast agents we synthetized several novel fluorinated bis-styrylbenzenes and studied their fluorescent properties and amyloid-ß binding characteristics. The compounds showed a high affinity for Aß plaques on murine and human brain sections. Interestingly, competitive binding experiments demonstrated that they bound to a different binding site than chrysamine G. Despite their high logP values, many bis-styrylbenzenes were able to enter the brain and label murine amyloid in vivo. Unfortunately initial post-mortem (19)F NMR studies showed that these compounds as yet do not warrant further MRI studies due to the reduction of the (19)F signal in the environment of the brain.

Hand-off orientation in oral pathology: Bridging the gap for better patient care.

The practice of hand-off orientation in oral pathology plays a pivotal role in ensuring efficient and high-quality patient care. Given the intricate nature of oral health, the seamless transition of patient care from one healthcare provider to another is critical. Hand-off orientation in oral pathology begins with a comprehensive referral of oral biopsy specimens from a general dentist or clinical specialist to the oral pathology laboratory. Obtaining detailed information about oral biopsy tissue and complete patient information from clinicians is indeed crucial for a variety of reasons, including accurate diagnosis and treatment planning. This collaborative approach ensures that patients receive timely and accurate care, reducing the potential for misdiagnosis or treatment delays. In the field of oral pathology, effective hand-off orientation is a cornerstone of patient safety and positive outcomes.

Nonlinear Elastic Bottlebrush Polymer Hydrogels Modulate Actomyosin Mediated Protrusion Formation in Mesenchymal Stromal Cells.

The nonlinear elasticity of many tissue-specific extracellular matrices is difficult to recapitulate without the use of fibrous architectures, which couple strain-stiffening with stress relaxation. Herein, bottlebrush polymers are synthesized and crosslinked to form poly(ethylene glycol)-based hydrogels and used to study how strain-stiffening behavior affects human mesenchymal stromal cells (hMSCs). By tailoring the bottlebrush polymer length, the critical stress associated with the onset of network stiffening is systematically varied, and a unique protrusion-rich hMSC morphology emerges only at critical stresses within a biologically accessible stress regime. Local cell-matrix interactions are quantified using 3D traction force microscopy and small molecule inhibitors are used to identify cellular machinery that plays a critical role in hMSC mechanosensing of the engineered, strain-stiffening microenvironment. Collectively, this study demonstrates how covalently crosslinked bottlebrush polymer hydrogels can recapitulate strain-stiffening biomechanical cues at biologically relevant stresses and be used to probe how nonlinear elastic matrix properties regulate cellular processes.

Elacytarabine (CP-4055) in the treatment of acute myeloid leukemia.

Elacytarabine (formerly CP-4055) is a lipid-conjugated derivative of the nucleoside analog cytarabine. Elacytarabine was rationally designed to circumvent cytarabine resistance related to decreased cellular uptake, due to the ability of the lipophilic drug moiety to enter the cell without the requirement of specialized nuclear transport proteins, including the hENT1. In preclinical and clinical studies, elacytarabine has demonstrated both safety and efficacy in acute myeloid leukemia (AML), with noteworthy activity among the cytarabine-refractory AML population. Elacytarabine was granted orphan drug designation status from the European Commission in 2007 and from the US FDA in 2008, with a fast-track approval designation from the FDA in 2010. Results of a recent randomized Phase III clinical trial, however, failed to show superiority of elacytarabine over the investigator's choice of therapy for relapsed or refractory AML.

Role of MMP1 and MMP10 in local invasion and distant metastasis in different levels of oral squamous cell carcinoma - A immunohistochemical comparative study.

Background: Matrix metalloproteinases (MMPs) are basically a part of a large family of proteolytic enzymes. They play an important role in degrading extracellular matrix and basement membrane, which is a basic mechanism in local invasion and tumour metastasis. The aim of this study was to evaluate immunohistochemically the expression of MMP1 and MMP10 in tumour invasion locally and at distant levels, including lymph nodes at different levels in oral squamous cell carcinoma (OSCC). Materials and Methods: A total of 50 tissue samples with clinically confirmed OSCC and 15 normal oral mucosal tissues will be included in the study. Immunohistochemical staining will be performed for the demonstration of MMP1 and MMP10 in lesional tissue, perilesional tissue, and lymph nodes of different levels that were evaluated with respect to microscopic features. Results: All OSCC cases had MMP1 and MMP10 expression levels. The expression increased as the nodal level increased from level I to level V. This difference was statistically significant at P < 0.001 Both MMPs were not expressed in normal epithelial cells. There was no significant correlation between MMP1 and MMP10 expression. Conclusion: This study showed that MMP1 and MMP10 are expressed in the tissues of OSCC and may serve as prognostic indicators for the disease.

Role of hypoxia and epithelial-mesenchymal transition in the formation and maintenance of oral cancer stem cells in oral squamous cell carcinomas and metastatic lymph node: An immunohistochemical analysis.

Background: Inspite of having advanced treatment modalities the overall survival rate in oral squamous cell carcinoma (OSCC) remains poor. This is considered to be mainly due to local recurrence and distant metastasis. Various studies have concentrated on the role of oral cancer stem cells (OCSCs) in the progression and metastasis of OSCC. However, the role of tumor microenvironment components has been less delved into. Hence clarity on cell biology and metastatic potential OCSCs is essential for the development of more effective anti-cancer treatment. Aim: To establish the role of OCSCs in different grades of OSCC and metastatic lymph nodes through the expression of cluster of differentiation 44 (CD44). To demonstrate and correlate the role of hypoxia and Epithelial mesenchymal transition (EMT) in the various grades and metastatic lymph nodes in the formation and maintenance of OCSCs by employing Hypoxia-inducible factor-1 Alpha (HIF 1α) and Snail respectively. Method and Material: A total of 36 cases of OSCC, 12 from each grade and 12 normal oral mucosal tissues were included in the study. Immunohistochemical staining was performed for the demonstration of CD44, HIF1α, and Snail. Statistics: Descriptive analysis, Chi-square, and Spearman's rank correlation were used to analyze frequency and proportion, to compare expression and correlate between lesion proper and lymph node in each group respectively. Results: Significant expression of CD44, HIF1 α, and Snail among advancing grades of OSCC and their metastatic lymph node were observed. A positive correlation was seen between them. Conclusions: The prognosis of OSCC can be improved by better understanding and targeting the molecules involved in the formation and maintenance of OCSCs.

Evaluation of Her-2 protein in histologically tumor-free margins of oral squamous cell carcinoma: An immunohistochemical study.

Background: The status of the 5-year survival rate and loco-regional recurrence in oral squamous cell carcinoma (OSCC) has remained unchanged over the decades. Recent advances in oral cancer research have revealed that the presence of molecular alterations in histologically tumor-free margins of OSCC has a prognostic significance and can aid in designing therapeutic strategies. However, the literature on molecular studies on histologically tumor-free margins is scant, especially in the Indian population. Considering the prognostic implications of Her-2 in malignancies of the breast, ovary, and OSCC, we aimed to assess the expression of Her-2 protein in histologically tumor-free margins of OSCC and to establish correlation with clinico-pathological parameters. Methods: 4 µ m thick sections from formalin-fixed paraffin-embedded tissue blocks of 40 histologically tumor-free margins of OSCC affecting the buccal mucosa and/or lower gingiva-buccal sulcus and 40 normal oral mucosa samples were subjected to immunohistochemical analysis for the Her-2 antibody. The obtained data were analyzed statistically. Results: The mean ages in study and control groups were 49.83 years (SD ± 10.43) and 37.28 years (SD ± 8.61), respectively, with male predominance. Local recurrence was seen in 52.5% of patients. Follow-up data revealed that a total of 71.4% of patients succumbed to mortality and all of them had reported local recurrence. Overall, the presence of local recurrence and the status of survival showed a statistically significant association (p = 0.0001). All the samples in the study and control groups were negative for Her-2 immuno-expression. Conclusion: The study indicated the lack of Her-2 immuno-expression in histologically tumor-free margins of OSCC with several speculated explanations. As it is a preliminary study, further studies employing both immunohistochemistry (IHC) and gene amplification in histologically tumor-free margins of OSCC affecting different anatomical sites are warranted. This will aid in identifying the subset of patients that may benefit from targeted therapy.

Jaw actinomycosis-An opportunistic infection: Case series.

Jaw actinomycosis is a quite rare invasive facultative bacterial infection caused by Actinomyces, Gram-positive filamentous bacilli found in human commensal. A break in continuity of epithelium due to surgery, trauma or previous infection can lead to deeper invasion of bacteria causing infection. The risk factors for actinomycosis are trauma, caries, debilitation, and poorly controlled diabetes mellitus. Clinical presentation can mimic other pathologies, such as fungal infection tuberculosis, granulomatous diseases, so the diagnosis of actinomycosis is delayed or misdiagnosed. For the definitive diagnosis of jaw actinomycosis, medical history, dental history histopathological examinations and microbiological culture are important parameters. Actinomycotic bacteria are sensitive to antibacterial agents hence chemotherapeutic agents are used for treatment. This report presents case series of jaw actinomycosis involving mandible and maxilla. The final diagnosis was supported by histopathology.

Buccal delivery of small molecules and biologics: Of mucoadhesive polymers, films, and nanoparticles - An update.

Buccal delivery of small and large molecules is an attractive route of administration that has been studied extensively over the past few decades. This route bypasses first-pass metabolism and can be used to deliver therapeutics directly to systemic circulation. Moreover, buccal films are efficient dosage forms for drug delivery due to their simplicity, portability, and patient comfort. Films have traditionally been formulated using conventional techniques, including hot-melt extrusion and solvent casting. However, newer methods are now being exploited to improve the delivery of small molecules and biologics. This review discusses recent advances in buccal film manufacturing, using the latest technologies, such as 2D and 3D printing, electrospraying, and electrospinning. This review also focuses on the excipients used in the preparation of these films, with emphasis on mucoadhesive polymers and plasticizers. Along with advances in manufacturing technology, newer analytical tools have also been used for the assessment of permeation of the active agents across the buccal mucosa, the most critical biological barrier and limiting factor of this route. Additionally, preclinical and clinical trial challenges are discussed, and some small molecule products already on the market are explored.

'Inverted' analogs of the antibiotic gramicidin S with an improved biological profile.

A series of gramicidin S derivatives 4-15 are presented that have four ornithine residues as polar protonated side chains and two central hydrophobic amino acids with unaltered turn regions. These peptides were screened against human erthrocytes and our standard panel of Gram negative- and Gram positive bacteria, including four MRSA strains. Based on the antibacterial- and hemolytic data, peptides 13 and 14 have an improved biological profile compared to the clinically applied topical antibiotic gramicidin S.

COVID-19 Associated Mucormycosis (CAM): A Single Hospital-Based Study.

Background: Opportunistic fungal infections like Mucormycosis in Coronavirus Disease 2019 (COVID-19) patients have posed a great challenge to health care professionals, especially in developing countries like India. Hence, there is a need to understand the biological behaviour of COVID-19 associated Mucormycosis (CAM) to establish standard treatment Protocols and to reduce mortality. Aims: This study aims is to assess the type of Mucormycosis among COVID-19 patients in study population and compare the findings with clinical, radiological and haematological parameters along with treatment and surgical management. Methods and Material: This retrospective, observational study included 60 cases of CAM reported to the Department of Oral and Maxillofacial Surgery at the tertiary care centre, Karnataka Institute of Medical Sciences, Hubli. Data about various parameters were tabulated and analysed statistically. Statistical Analysis Used: Bivariate analysis was done using the Chi-Square test to assess the relationship between the type of Mucormycosis and other variables. Spearman's Correlation test was used to assess the correlation between types of Mucormycosis with the other variables. Linear regression analysis was performed to assess the response variable related to the type of Mucormycosis. Results: About 50% of subjects presented with "Rhino orbital" type of Mucormycosis. Palatal discoloration and palatal erosion was the most common oral manifestation among "only Sinus" and "Rhino orbital" types of Mucormycosis (P = 0.00). Significant association (P = 0.29) was found between the type of Diabetes mellitus and Mucormycosis. Conclusions: The study indicates that DM is the most commonly associated comorbidity in CAM patients. Hence, a thorough understanding of the underlying comorbidity and its close monitoring during and after COVID-19 infection is mandatory for successful treatment outcomes.

Granular PEG hydrogels mediate osteoporotic MSC clustering via N-cadherin influencing the pro-resorptive bias of their secretory profile.

Postmenopausal osteoporosis results from a pro-resorptive bone environment, which decreases bone mineral density causing increased fracture risk. Bone marrow derived mesenchymal stem/stromal cells (MSCs) secrete factors involved in bone homeostasis, but osteoporosis mediated changes to their secretions remain understudied. Herein, we examined the secretome of MSCs isolated from ovariectomized rats (OVX rMSCs), a model of post-menopausal osteoporosis, as a function of cell-cell interactions. Specifically, we controlled clustering of OVX and SHAM rMSCs by assembling them in granular hydrogels synthesized from poly(ethylene glycol) microgels with average diameters of ∼10, 100, and 200 µm. We directed both the sizes of rMSC clusters (single cells to ∼30 cells/cluster) and the percentages of cells within clusters (∼20-90%) by controlling the scaffold pore dimensions. Large clusters of OVX rMSCs had a pro-resorptive secretory profile, with increased concentrations of Activin A, CXCL1, CX3CL1, MCP-1, TIMP-1, and TNF-ɑ, compared to SHAM rMSCs. As this pro-resorptive bias was only observed in large cell clusters, we characterized the expression of several cadherins, mediators of cell-cell contacts. N-cadherin expression was elevated (∼4-fold) in OVX relative to SHAM rMSCs, in both cell clusters and single cells. Finally, TIMP-1 and MCP-1 secretion was only decreased in large cell clusters of OVX rMSCs when N-cadherin interactions were blocked, highlighting the dependence of OVX rMSC secretion of pro-resorptive cytokines on N-cadherin mediated cell-cell contacts. Further elucidation of the N-cadherin mediated osteoporotic MSC secretome may have implications for developing therapies for postmenopausal osteoporosis. STATEMENT OF SIGNIFICANCE: Postmenopausal osteoporosis is a prevalent bone disorder that affects tens of millions of women worldwide. This disease is characterized by severe bone loss resulting from a pro-resorptive bone marrow environment, where the rates of bone resorption outpace the rates of bone deposition. The paracrine factors secreted by bone marrow MSCs can influence cell types responsible for bone homeostasis, but the osteoporosis-mediated changes to MSC secretory properties remains understudied. In this study, we used PEG-based porous granular scaffolds to study the influence of cell clustering on the secretory properties of osteoporotic MSCs. We observed increased secretion of several pro-resorptive factors by osteoporotic MSCs in large clusters. Further, we explored the dependence of this altered secretion profile on N-cadherin mediated cell-cell contacts.