Deep learning and remote photoplethysmography powered advancements in contactless physiological measurement.

In recent decades, there has been ongoing development in the application of computer vision (CV) in the medical field. As conventional contact-based physiological measurement techniques often restrict a patient's mobility in the clinical environment, the ability to achieve continuous, comfortable and convenient monitoring is thus a topic of interest to researchers. One type of CV application is remote imaging photoplethysmography (rPPG), which can predict vital signs using a video or image. While contactless physiological measurement techniques have an excellent application prospect, the lack of uniformity or standardization of contactless vital monitoring methods limits their application in remote healthcare/telehealth settings. Several methods have been developed to improve this limitation and solve the heterogeneity of video signals caused by movement, lighting, and equipment. The fundamental algorithms include traditional algorithms with optimization and developing deep learning (DL) algorithms. This article aims to provide an in-depth review of current Artificial Intelligence (AI) methods using CV and DL in contactless physiological measurement and a comprehensive summary of the latest development of contactless measurement techniques for skin perfusion, respiratory rate, blood oxygen saturation, heart rate, heart rate variability, and blood pressure.

Complex Hand Reconstruction using a Novel Two-stage Temporary Ectopic Implantation of the Contralateral Upper Limb.

Ectopic transplantation of the hand remains a rare, innovative yet valuable operation in select cases of trauma and amputation. We aim to describe a novel technique of complex hand reconstruction using a two-stage ectopic implantation of the contralateral upper limb. A male patient with a near complete avulsion amputation of the right upper limb at the level of the mid-forearm and a crushing injury to his left hand was admitted after a farming accident. The right palm was ectopically transplanted to the left lower limb and both upper limbs underwent debridement with vacuum assisted dressings (VACs). There was eventual dieback of the left thumb, ring and little finger with a large palmar soft tissue defect that was eventually reconstructed using segments of the ectopically transplanted limb in two separate operations. The patient made an uneventful postoperative recovery and managed to regain protective sensation and gross motor function of his reconstructed hand.

Investigations into the role of platelet-activating factor (PAF) in the peri-conception period of the mare.

Platelet-activating factor (PAF) has been implicated in a number of reproductive processes ranging from ovulation to embryo motility, but has not been widely explored in the mare. To identify the presence and examine the role of PAF in the equine periconception processes, targeted mass spectrometry coupled with chromatographic separation (LC-MS/MS) was performed on equine follicular fluid (FF), and PAF was quantitatively detected. Subsequently, untargeted high-resolution mass spectrometry-based lipidomic analysis was carried out to quantify PAF in different sized pre-ovulatory follicles, whereby different molecular species of PAF, PAF(14:0) and PAF(16:1), were both seen to be increasing with follicle diameter. These findings suggest that PAF within FF is increasing as preovulatory follicles approach ovulation. Additionally, immunofluorescence staining identified the PAF Receptor (PAFR) in the luminal pericellular, apical and basal aspect of equine oviductal epithelial cells. Lastly, an equine oviductal epithelial organoid model was generated, and showed that the addition of PAF significantly increased the ciliary beat frequency (CBF) (Hz), an action consistent with a role for PAF in embryo migration. It is proposed that the local action of PAF on the ciliated cells of the oviduct propels both the oocyte and the conceptus towards the uterus. In the mare, it appears that PAF is a contributor during the periconception period, potentially being a mediator in the mechanisms of ovulation and in the dialogue of very early pregnancy.

Therapeutic potential of extracellular vesicles derived from human amniotic epithelial cells for perinatal cerebral and pulmonary injury.

Lung and brain injury that occurs during the perinatal period leads to lifelong disability and is often driven and/or exacerbated by inflammation. Human amniotic epithelial cells (hAEC), which demonstrate immunomodulatory, anti-fibrotic, and regenerative capabilities, are being explored as a therapeutic candidate for perinatal injury. However, limitations regarding scalable manufacturing, storage, transport, and dose-related toxicity have impeded clinical translation. Isolated therapeutic extracellular vesicles (EVs) from stem and stem-like cells are thought to be key paracrine mediators of therapeutic efficacy. The unique characteristics of EVs suggest that they potentially circumvent the limitations of traditional cell-based therapies. However, given the novelty of EVs as a therapeutic, recommendations around ideal methods of production, isolation, storage, and delivery have not yet been created by regulatory agencies. In this concise review, we discuss the pertinence and limitations of cell-based therapeutics in perinatal medicine. We also review the preclinical evidence supporting the use of therapeutic EVs for perinatal therapy. Further, we summarize the arising considerations regarding adequate cell source, biodistribution, isolation and storage methods, and regulatory roadblocks for the development of therapeutic EVs.

Kinetic analysis of T4 polynucleotide kinase via isothermal titration calorimetry.

T4 polynucleotide kinase (T4 PNK) phosphorylates the 5'-terminus of DNA and RNA substrates. It is widely used in molecular biology. Single nucleotides can serve as substrates if a 3'-phosphate group is present. In this study, the T4 PNK-catalyzed conversion of adenosine 3'-monophosphate (3'-AMP) to adenosine-3',5'-bisphosphate was characterized using isothermal titration calorimetry (ITC). Although ITC is typically used to study ligand binding, in this case the instrument was used to evaluate enzyme kinetics by monitoring the heat production due to reaction enthalpy. The reaction was initiated with a single injection of 3'-AMP substrate into the sample cell containing T4 PNK and ATP at pH 7.6 and 30 °C, and Michaelis-Menten analysis was performed on the reaction rates derived from the plot of differential power versus time. The Michaelis-Menten constant, KM, was 13 µM, and the turnover number, kcat, was 8 s-1. The effect of inhibitors was investigated using pyrophosphate (PPi). PPi caused a dose-dependent decrease in the apparent kcat and increase in the apparent KM under the conditions tested. Additionally, the intrinsic reaction enthalpy and the activation energy of the T4 PNK-catalyzed phosphorylation of 3'-AMP were determined to be -25 kJ/mol and 43 kJ/mol, respectively. ITC is seldom used as a tool to study enzyme kinetics, particularly for technically-challenging enzymes such as kinases. This study demonstrates that quantitative analysis of kinase activity can be amenable to the ITC single injection approach.

Human Amniotic Epithelial Cell Transplantation is Safe and Well Tolerated in Patients with Compensated Cirrhosis: A First-in-Human Trial.

Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts. Cohort 1 patients received 0.5 × 106/kg hAEC in one IV infusion. Cohort 2 patients received 1 × 106/kg hAEC in one IV infusion. The patients in cohort 3 received 1 × 106/kg hAEC on days 0 and 28. Here, we report follow-up to post-infusion day 56 (D56), during which no serious adverse events occurred. Six patients experienced no study-related adverse events, while 3 patients reported mild (grade 1) headaches that were possibly infusion-related. A transient decrease in serum platelet count occurred in all patients, which returned to baseline screening values by day 5. FIB-4 values to assess fibrosis were significantly lower at D56. Although not statistically significant, serum AST levels and liver stiffness measurements at D56 were lower than those at baseline. The hepatic venous pressure gradient, a measure of portal hypertension, declined in 4 patients, did not change in 3 patients, and increased in 2 patients. In conclusion, intravenous infusion of allogeneic hAEC in patients with compensated cirrhosis at the doses used in this study was safe and well tolerated, with no difference observed between 1 and 2 doses. Decreased hepatic inflammation, liver stiffness, and portal hypertension support larger studies aimed at identifying patients who may benefit from this therapy. Clinical Trial registration: The trial was prospectively entered on the Australian Clinical Trials Registry (ANZCTR12616000437460).

Artificial intelligence powered advancements in upper extremity joint MRI: A review.

Magnetic resonance imaging (MRI) is an indispensable medical imaging examination technique in musculoskeletal medicine. Modern MRI techniques achieve superior high-quality multiplanar imaging of soft tissue and skeletal pathologies without the harmful effects of ionizing radiation. Some current limitations of MRI include long acquisition times, artifacts, and noise. In addition, it is often challenging to distinguish abutting or closely applied soft tissue structures with similar signal characteristics. In the past decade, Artificial Intelligence (AI) has been widely employed in musculoskeletal MRI to help reduce the image acquisition time and improve image quality. Apart from being able to reduce medical costs, AI can assist clinicians in diagnosing diseases more accurately. This will effectively help formulate appropriate treatment plans and ultimately improve patient care. This review article intends to summarize AI's current research and application in musculoskeletal MRI, particularly the advancement of DL in identifying the structure and lesions of upper extremity joints in MRI images.

Current concepts and new trends in management of isolated triangular fibrocartilage complex injuries.

The triangular fibrocartilaginous complex is made of multiple components, of which the palmar and dorsal radioulnar ligaments play an important role in distal radioulnar joint stability. The ulnar wrist ligaments may be injured during forearm and wrist trauma. There are several aspects of triangular fibrocartilaginous complex management that are still open to debate. The aim of the present study was to review the current concepts and discuss emerging trends to better elucidate and treat this important ligament complex.Level of evidence: V.

Stem Cell Derived Extracellular Vesicle Therapy for Multiple Sclerosis, A Systematic Review and Meta-Analysis of Preclinical Studies.

Stem cell therapy holds promise for multiple sclerosis (MS), with efficacy of different stem cell types reported across a range of preclinical MS animal models. While stem cell therapy has been approved for a small number of diseases in humans, extracellular vesicles (EVs) may provide an efficacious, cost-effective, and safer alternative to stem cell therapy. To this end, we conducted a systematic review with meta-analysis to assess the effectiveness of stem cell-derived secretome (EV and conditioned media (CM)) in animal models of MS. The data were extracted to calculate standardized mean differences for primary outcome measure of disease severity, using a random effect model. Additionally, several subgroup analyses were conducted to assess the impact of various study variables such as stem cell type and source, stem cell modification, route and time of administration, number of animals and animal's age, and EV isolation methods on secondary outcome. Publication quality and risk of bias were assessed. Overall, 19 preclinical studies were included in the meta-analysis where stem cell EV/CM was found to significantly reduce disease severity in EV-treated (SMD = 2, 95% CI: 1.18-2.83, P < .00001) and CM-treated animals (SMD = 2.58, 95% CI: 1.34-3.83, P < .00001) compared with controls. Our analysis indicated that stem cell secretome has a positive effect on reducing demyelination, systemic neuroinflammation, and disease severity in preclinical models of MS. These findings indicate a potential therapeutic effect that merits investigation and validation in clinical settings.

A methylation-phosphorylation switch controls EZH2 stability and hematopoiesis.

The Polycomb Repressive Complex 2 (PRC2) methylates H3K27 to regulate development and cell fate by transcriptional silencing. Alteration of PRC2 is associated with various cancers. Here, we show that mouse Kdm1a deletion causes a dramatic reduction of PRC2 proteins, whereas mouse null mutation of L3mbtl3 or Dcaf5 results in PRC2 accumulation and increased H3K27 trimethylation. The catalytic subunit of PRC2, EZH2, is methylated at lysine 20 (K20), promoting EZH2 proteolysis by L3MBTL3 and the CLR4DCAF5 ubiquitin ligase. KDM1A (LSD1) demethylates the methylated K20 to stabilize EZH2. K20 methylation is inhibited by AKT-mediated phosphorylation of serine 21 in EZH2. Mouse Ezh2K20R/K20R mutants develop hepatosplenomegaly associated with high GFI1B expression, and Ezh2K20R/K20R mutant bone marrows expand hematopoietic stem cells and downstream hematopoietic populations. Our studies reveal that EZH2 is regulated by methylation-dependent proteolysis, which is negatively controlled by AKT-mediated S21 phosphorylation to establish a methylation-phosphorylation switch to regulate the PRC2 activity and hematopoiesis.

Human amnion epithelial cell therapy reduces hypertension-induced vascular stiffening and cognitive impairment.

Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8-12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9-11, P < 0.05). Administration of amnion epithelial cells attenuated these effects of angiotensin II (P < 0.05). Angiotensin II-induced cognitive impairment was prevented by amnion epithelial cell therapy (n = 7-9, P < 0.05). In the brain, amnion epithelial cells modulated some of the inflammatory genes that angiotensin II promoted differential expression of (n = 6, p-adjusted < 0.05). These findings suggest that amnion epithelial cells could be explored as a potential therapy to inhibit vascular pathology and cognitive impairment during hypertension.

Locally Invasive Pigmented Villonodular Synovitis of the Wrist Treated by Arthroscopic Resection and Bone Grafting.

Pigmented villonodular synovitis (PVNS) is a benign but locally aggressive neoplasm that can affect tendon sheath, bursae, or joint. The wrist joint however is uncommonly involved and here we present a case of chronic monoarticular joint pain and swelling in a healthcare professional that was later histologically verified to be PVNS of the radiocarpal joint. The patient had a magnetic resonance imaging (MRI) performed prior to surgery which showed a locally invasive bony tumor of the scaphoid. He subsequently underwent a wrist arthroscopic evaluation and resection with bone grafting as the index surgery and made an uneventful postoperative recovery. This is a novel technique to address PVNS of the wrist as these cases are usually managed using open procedures which can lead to additional scarring and disrupt the blood supply of the joint capsule.

Implications of maternal-fetal health on perinatal stem cell banking.

Cell based therapies are being assessed for their therapeutic potential across a variety of diseases. Gestational tissues are attractive sources for cell therapy. The large number of births worldwide ensures sufficient access to gestational tissues, however, limited information has been reported around the impact of birth trends, delivery methods and pregnancy conditions on perinatal stem cell banking. This review describes the current state of banking of gestational tissues and their derived perinatal stem cells, discusses why the changes in birth trends and delivery methods could affect gestational tissue banking practices, and further explores how common pregnancy complications can potentially influence perinatal stem cell banking.

A comparative cadaveric study for percutaneous scaphoid fixation: robotic vs freehand.

PURPOSES: To compare the robotic-assisted and the traditional freehand percutaneous scaphoid fixation in number of guidewire attempts, duration of fluoroscopy time, amount of radiation dose, and screw centrality. METHODS: Twenty cadaveric specimens were randomized into either the robotic or freehand group. The scaphoids in both groups were fixed by either the same attending or resident from our hand surgery department. The operation duration, amount of radiation from intraoperative fluoroscopy, total fluoroscopy time, and the number of guidewire attempts were documented and compared. Postoperatively, all the specimens had a computed tomography (CT) scan performed, and the difference in the final position of the screw and the central axis of the scaphoid was examined. RESULTS: In the robotic group, all the guide wires were satisfactorily positioned within a single attempt, while the median number of attempts in the traditional freehand group was 18 (quaternion 14-65). This also meant that the surgeon in the robotic group experienced significantly lower radiation exposure dose and time as compared to the freehand group. There were no significant differences in the final screw position as compared to the central axis of the scaphoid in both groups. Although there was no difference in surgeon performance in the robotic group, the operative time for the attending was significantly lower as compared to the resident in the freehand group. CONCLUSION: Robotic-assisted surgery for scaphoid fracture fixation is superior to the traditional freehand method as it facilitates accurate screw placement with lower radiation exposure and fewer guide wire attempts.

Arthroscopic Bone Grafting and Robot-assisted Fixation for Scaphoid Nonunion.

OBJECTIVES: Scaphoid nonunion remains a challenging problem to manage with no general consensus on its treatment recommendations. We propose a novel minimally invasive (MIS) technique of arthroscopic bone grafting (ABG) with robot-assisted fixation for the treatment of scaphoid nonunions. METHODS: Patients with radiographically proven scaphoid nonunion treated by this novel surgical technique were included. Following arthroscopic debridement and iliac crest bone grafting, the scaphoid was fixed percutaneously using either multiple Kirschner (K)-wires or a headless compression screw using a robotic navigation system. RESULTS: Six male patients with an average age of 29.2 years were enrolled. Four patients had scaphoid waist fractures, and the other two were proximal pole fractures. During wrist arthroscopy, punctate bleeding of the proximal scaphoid fragment was observed in four out of the six patients. Half of the patients were fixed using a headless compression screw and the other half using multiple K-wires. All the guidewires were placed with a single-attempt using the robotic navigation system. Postoperatively, all the scaphoid fractures had complete radiographic union by 16 weeks. At a mean follow-up of 18.3 months, there were significant improvements in wrist range of motion, grip strength, and patient-rated outcomes. No intraoperative or early postoperative complications were encountered in any of our patients. CONCLUSION: Arthroscopic bone grafting with robot-assisted fixation is a feasible and promising therapeutic option for scaphoid nonunions, regardless of the vascularity of the proximal pole fragment. This novel technique allows for anatomic restoration of the scaphoid alignment and accurate, targeted placement of implants into the scaphoid nonunion site within a single-attempt using a robotic navigation system.

A Novel Technique of Arthroscopic-Assisted Four-Corner Fusion and Robot-Assisted Fixation for Scaphoid Nonunion Advanced Collapse Wrist: A Single Case Study.

OBJECTIVE: Scaphoid nonunion advanced collapse (SNAC) is a relatively common and debilitating wrist disorder yet its treatment remains challenging and controversial. We aim to describe a novel technique of a dual arthroscopic and robotic assisted four-corner fusion (4CF) in the treatment of SNAC wrist. METHODS: In this study, we describe an original arthroscopic and robotic assisted 4CF, which is novel and currently unpublished in literature. The surgical approach included these predefined steps: arthroscopic resection of the scaphoid, radial styloid and of diseased cartilage between the capitate-lunate joint and triquetrum-hamate joint, correction of Dorsal Intercalated Segment Instability (DISI) deformity of the wrist and robotic assisted 4CF performed percutaneously with screws. Dynamic fluoroscopic imaging with the mini C-arm was performed five times and the 3D scanning machine was used once. RESULTS: Our patient with SNAC II wrist was 57 years old at the time of initial presentation with a history of untreated traumatic wrist injury approximately 20 years ago. Regular wrist X-rays were performed at the outpatient setting and a computed tomography (CT) of the wrist was performed at the third postoperative month to confirm bony union. The patient's wrist range of motion (ROM), grip strength, Visual Analog Scale (VAS) score, Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, Modified Mayo Wrist Score (MMWS), and Patient Rated Wrist Evaluation (PRWE) were also evaluated during short-term follow-up at 6 months. During the patient's review at 6 months, his VAS score was 0 with complete pain relief. His wrist flexion was 20° and wrist extension at 45°. His pronation-supination was normal and comparable to his uninjured contralateral wrist. His operated wrist which was also his dominant hand had a grip strength of 22 kg as compared with 28 kg of the unaffected hand. He also had a Mayo Wrist Score of 85, QuickDASH score of 2.3 and PRWE of 6, and resumed his occupation as a clerk at 3 months. CONCLUSIONS: This dual arthroscopic and robotic assisted 4CF is a novel surgical method worth considering in the treatment of SNAC II wrists. It is minimally invasive and allows for accurate placement of the screws in a single attempt. There was bony union by the third postoperative month as confirmed by CT imaging and excellent resolution of symptoms.

Local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal Crohn's disease: a phase I open label study with long-term follow up.

BACKGROUND: Local fistula injection of mesenchymal stromal/stem cells (MSC) is effective for complex perianal Crohn's fistulas but is also expensive and requires specialised facilities for cell revival before administration. Human amnion epithelial cells (hAEC) are non-MSC cells with therapeutic properties. The primary aim of this study was safety of hAEC therapy. Secondary aims included hAEC efficacy, feasibility of the protocol and impact on quality of life. METHODS: A phase I open label study of ten adults with active complex Crohn's perianal fistulas refractory to conventional treatment, including anti-tumour necrosis factor alpha therapy, was undertaken. A single dose of hAEC was injected into the fistula tract(s) after surgical closure of the internal opening(s). Study outcomes were assessed at week 24 with follow up for at least 52 weeks. FINDINGS: Local injection of hAEC was safe, well tolerated and the injection procedure was feasible. Complete response occurred in 4 patients, and a partial response in an additional 4 patients. There was a mean reduction in the Perianal Disease Activity Index of 6.5 points (95% CI -9.0 to -4.0, p = 0.0002, paired t-test), modified Van Assche MRI Index of 2.3 points (95% CI -3.9 to -0.6, p = 0.012, paired t-test) and a mean improvement of 15.8 points (95% CI 4.9 to 26.8, p = 0.010, paired t-test) in quality of life using the Short IBD-Questionnaire in complete responders. INTERPRETATION: Local injection of hAEC therapy for refractory complex perianal fistulising Crohn's disease appears safe, well-tolerated, feasible and demonstrated improvement. Quality of life is improved in those who achieve complete fistula healing. FUNDING: This study was funded by competitive research grant funding from the Gastroenterological Society of Australia Seed Grant 2018.

Corrigendum: Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT).

[This corrects the article DOI: 10.3389/fnins.2023.1153231.].

Aged mice are less susceptible to motion sickness and show decreased efferent vestibular activity compared to young adults.

INTRODUCTION: The efferent vestibular system (EVS) is a feedback circuit thought to modulate vestibular afferent activity by inhibiting type II hair cells and exciting calyx-bearing afferents in the peripheral vestibular organs. In a previous study, we suggested EVS activity may contribute to the effects of motion sickness. To determine an association between motion sickness and EVS activity, we examined the effects of provocative motion (PM) on c-Fos expression in brainstem efferent vestibular nucleus (EVN) neurons that are the source of efferent innervation in the peripheral vestibular organs. METHODS: c-Fos is an immediate early gene product expressed in stimulated neurons and is a well-established marker of neuronal activation. To study the effects of PM, young adult C57/BL6 wild-type (WT), aged WT, and young adult transgenic Chat-gCaMP6f mice were exposed to PM, and tail temperature (Ttail ) was monitored using infrared imaging. After PM, we used immunohistochemistry to label EVN neurons to determine any changes in c-Fos expression. All tissue was imaged using laser scanning confocal microscopy. RESULTS: Infrared recording of Ttail during PM indicated that young adult WT and transgenic mice displayed a typical motion sickness response (tail warming), but not in aged WT mice. Similarly, brainstem EVN neurons showed increased expression of c-Fos protein after PM in young adult WT and transgenic mice but not in aged cohorts. CONCLUSION: We present evidence that motion sickness symptoms and increased activation of EVN neurons occur in young adult WT and transgenic mice in response to PM. In contrast, aged WT mice showed no signs of motion sickness and no change in c-Fos expression when exposed to the same provocative stimulus.

Substrate mechanical properties bias MSC paracrine activity and therapeutic potential.

Mesenchymal stromal cells (MSCs) have significant therapeutic potential due to their ability to differentiate into musculoskeletal lineages suitable for tissue-engineering, as well as the immunomodulatory and pro-regenerative effects of the paracrine factors that these cells secrete. Cues from the extracellular environment, including physical stimuli such as substrate stiffness, are strong drivers of MSC differentiation, but their effects upon MSC paracrine activity are not well understood. This study, therefore sought to determine the impact of substrate stiffness on the paracrine activity of MSCs, analysing both effects on MSC fate and their effect on T-cell and macrophage activity and angiogenesis. The data show that conditioned medium (CM) from MSCs cultured on 0.2 kPa (soft) and 100 kPa (stiff) polyacrylamide hydrogels have differing effects on MSC proliferation and differentiation, with stiff CM promoting proliferation whilst soft CM promoted differentiation. There were also differences in the effects upon macrophage phagocytosis and angiogenesis, with the most beneficial effects from soft CM. Analysis of the media composition identified differences in the levels of proteins including IL-6, OPG, and TIMP-2. Using recombinant proteins and blocking antibodies, we confirmed a role for OPG in modulating MSC proliferation with a complex combination of factors involved in the regulation of MSC differentiation. Together the data confirm that the physical microenvironment has an important influence on the MSC secretome and that this can alter the differentiation and regenerative potential of the cells. These findings can be used to tailor the culture environment for manufacturing potent MSCs for specific clinical applications or to inform the design of biomaterials that enable the retention of MSC activity after delivery into the body. STATEMENT OF SIGNIFICANCE: • MSCs cultured on 100 kPa matrices produce a secretome that boosts MSC proliferation • MSCs cultured on 0.2 kPa matrices produce a secretome that promotes MSC osteogenesis and adipogenesis, as well as angiogenesis and macrophage phagocytosis • IL-6 secretion is elevated in MSCs on 0.2 kPa substrates • OPG, TIMP-2, MCP-1, and sTNFR1 secretion are elevated in MSCs on 100 kPa substrates.