Impact of sagittal and coronal pelvic tilt on hip subluxation in non-ambulatory flaccid neuromuscular scoliosis patients following spinal correction.

PURPOSE: To evaluate the actual change in clinical hip pain and hip migration after operation for non-ambulatory flaccid neuromuscular (NM) scoliosis and investigate whether there is an association between hip migration and coronal/sagittal pelvic tilt (CO-PT/SA-PT). PATIENTS AND METHODS: This retrospective, single-center, observational study evaluated a total of 134 patients with non-ambulatory flaccid neuromuscular scoliosis who underwent surgery performed by a single surgeon between 2003 and 2020, with at least 2 years of follow-up period. Operation procedures were conducted in two stages, beginning with L5-S1 anterior release followed by posterior fixation. Radiologic parameters were measured at preoperative, immediate postoperative, and last follow-up periods with clinical hip pain and clinical hip dislocation events. RESULTS: The significant improvements occurred in various parameters after correction surgery for NM scoliosis, containing Cobb's angle of major curve and CO-PT. However, Reimer's hip migration percentage (RMP) was increased on both side of hip (High side, 0.23 ± 0.16 to 0.28 ± 0.21; Low side, 0.20 ± 0.14 to 0.23 ± 0.18). Hip pain and dislocation events were also increased (Visual analog scale score, 2.5 ± 2.3 to 3.6 ± 2.6, P value < 0.05; dislocation, 6-12). Logistic regression analysis of the interactions between ΔRMP(High) and the change of sagittal pelvic tilt (ΔSA-PT) after correction reveals a significant negative association. (95% CI 1.003-1.045, P value = 0.0226). CONCLUSIONS: In cases of non-ambulatory flaccid NM scoliosis, clinical hip pain, and subluxation continued to deteriorate even after correction of CO-PT. There was a relationship between the decrease in SA-PT, and an increase in hip migration percentage on high side, indicating the aggravation of hip subluxation.

Accelerated Fusion Dynamics by Recombinant Human Bone Morphogenetic Protein-2 Following Transforaminal Lumbar Interbody Fusion, Particularly in Osteoporotic Conditions.

BACKGROUND CONTEXT: Early fusion is crucial in interbody procedures to minimize mechanical complications resulting from delayed union, especially for patients with osteoporosis. Bone morphogenetic proteins (BMPs) are used in spinal fusion procedures; however, limited evaluation exists regarding time-to-fusion for BMP use, particularly in patients with osteoporosis. PURPOSE: To evaluate the difference in time-to-fusion after single-level transforaminal lumbar interbody fusion (TLIF) surgery between recombinant human bone morphogenetic protein-2 (rhBMP-2) usage and non-usage groups according to bone density. STUDY DESIGN: Retrospective single-center cohort study PATIENT SAMPLE: This study enrolled 132 patients (mean age, 65.25±8.66; male patients, 40.9%) who underwent single-level TLIF for degenerative disorders between February 2012 and December 2021, with pre- and postoperative computed tomography (CT). OUTCOME MEASURE: The interbody fusion mass and bone graft status on postoperative CT scans was obtained annually, and time-to-fusion was recorded for each patient. METHODS: The patients were divided into two groups based on rhBMP-2 use during the interbody fusion procedure. Patients were further divided into osteoporosis, osteopenia, and normal groups based on preoperative L1 vertebral body attenuation values, using cutoffs of 90 and 120 Hounsfield units. It was strictly defined that fusion is considered complete when a trabecular bone bridge was formed, and therefore, the time-to-fusion was measured in years. Time-to-fusion was statistically compared between BMP group and non-BMP groups, followed by further comparison according to bone density. RESULTS: The time-to-fusion differed significantly between BMP and non-BMP groups, with half of the patients achieving fusion within 2.5 years in the BMP group compared with 4 years in the non-BMP group (p < 0.001). The fusion rate varied based on bone density, with the maximum difference observed in the osteoporosis group, when half of the patients achieved fusion within 3 years in the BMP group compared to 5 years in the non-BMP group (p < 0.001). Subgroup analysis was conducted, revealing no significant associations between time-to-fusion and factors known to influence the fusion process, including age, gender, medical history, smoking and alcohol use, and medication history, except for rh-BMP2 use and bone density. CONCLUSIONS: RhBMP-2 usage significantly reduced time-to-fusion in single-level TLIF, especially in patients with osteoporosis. LEVEL OF EVIDENCE: Level III.

FAK regulates tension transmission to the nucleus and endothelial transcriptome independent of kinase activity.

The mechanical environment generated through the adhesive interaction of endothelial cells (ECs) with the matrix controls nuclear tension, preventing aberrant gene synthesis and the transition from restrictive to leaky endothelium, a hallmark of acute lung injury (ALI). However, the mechanisms controlling tension transmission to the nucleus and EC-restrictive fate remain elusive. Here, we demonstrate that, in a kinase-independent manner, focal adhesion kinase (FAK) safeguards tension transmission to the nucleus to maintain EC-restrictive fate. In FAK-depleted ECs, robust activation of the RhoA-Rho-kinase pathway increased EC tension and phosphorylation of the nuclear envelope protein, emerin, activating DNMT3a. Activated DNMT3a methylates the KLF2 promoter, impairing the synthesis of KLF2 and its target S1PR1 to induce the leaky EC transcriptome. Repleting FAK (wild type or kinase dead) or inhibiting RhoA-emerin-DNMT3a activities in damaged lung ECs restored KLF2 transcription of the restrictive EC transcriptome. Thus, FAK sensing and control of tension transmission to the nucleus govern restrictive endothelium to maintain lung homeostasis.

Association of Untreated Pre-surgical Depression With Pain and Outcomes After Spinal Surgery.

STUDY DESIGN: Prospective Cohort Study. OBJECTIVE: Untreated pre-surgical depression may prolong post-surgical pain and hinder recovery. However, research on the impact of untreated pre-surgical depression on post-spinal surgery pain is lacking. Therefore, this study aimed to assess pre-surgical depression in patients and analyze its relationship with post-surgical pain and overall post-surgical outcomes. METHODS: We recruited 100 patients scheduled for lumbar spine surgery due to spondylolisthesis, degenerative lumbar disc diseases, and herniated lumbar disc diseases. Psychiatrists evaluated them for the final selection. We assessed the Beck Depression Inventory (BDI), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and EuroQoL 5 Dimensions (EQ-5D) scores, numerical back and leg pain scales, and medication dosage data collected before and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Ninety-one patients were included in this study; 40 and 51 were allocated to the control and depression groups, respectively. The pre- and post-surgical leg pain, back pain, and functional scores were not different. However, the depression group showed higher ODI and EQ-5D and lower JOA scores than the control group 3 months post-surgery. Partial correlation analysis revealed an inverse correlation between the JOA and BDI scores and a positive correlation between the EQ-5D and BDI scores at 3 months postoperatively. CONCLUSION: Untreated depression can prolong postoperative pain and hinder recovery. Detecting and treating depression in patients before spine surgery may improve their overall quality of life and functional recovery.

Long-Term Incidence of Adjacent Segmental Pathology After Minimally Invasive vs. Open Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the incidence of adjacent segmental pathology (ASP) following minimally invasive (MI) vs open transforaminal lumbar interbody fusion (TLIF) and to identify factors linked to ASP requiring reoperation. METHODS: This retrospective study reviewed the outcomes of patients who underwent MI-TLIF or open TLIF. Radiographic ASP (RASP) was evaluated using X-ray imaging to distinguish between degenerative changes, spondylolisthesis, and instability in the adjacent spinal segment. Clinical ASP (CASP) was assessed with the visual analog scale score for leg and back pain and the Oswestry disability index. Patient data were collected 1, 2, 5, and 10 years postoperatively. The timing and frequency of ASP reoperation were analyzed. RESULTS: Five years postoperatively, the RASP rate was 35.23% and 45.95% in the MI-TLIF and open TLIF groups. The frequency of CASP differed significantly between the MI-TLIF and open TLIF groups at 1 year postoperatively. The rates of RASP, CASP, and ASP necessitating reoperation were not significantly different 10 years postoperatively. Cranial facet violation significantly affected ASP in both groups. In the open TLIF group, preoperative adjacent segment disc degeneration significantly influenced ASP. CONCLUSION: The RASP rate at 5 years postoperatively and the CASP rate at 1 year postoperatively differed significantly between groups. There was no difference in the rate of ASP requiring reoperation. Cranial facet violation is a crucial driving factor for ASP after both surgical procedures.

Autonomous Artificial Olfactory Sensor Systems with Homeostasis Recovery via a Seamless Neuromorphic Architecture.

Neuromorphic olfactory systems have been actively studied in recent years owing to their considerable potential in electronic noses, robotics, and neuromorphic data processing systems. However, conventional gas sensors typically have the ability to detect hazardous gas levels but lack synaptic functions such as memory and recognition of gas accumulation, which are essential for realizing human-like neuromorphic sensory system. In this study, a seamless architecture for a neuromorphic olfactory system capable of detecting and memorizing the present level and accumulation status of nitrogen dioxide (NO2) during continuous gas exposure, regulating a self-alarm implementation triggered after 147 and 85 s at a continuous gas exposure of 20 and 40 ppm, respectively. Thin-film-transistor type gas sensors utilizing carbon nanotube semiconductors detect NO2 gas molecules through carrier trapping and exhibit long-term retention properties, which are compatible with neuromorphic excitatory applications. Additionally, the neuromorphic inhibitory performance is also characterized via gas desorption with programmable ultraviolet light exposure, demonstrating homeostasis recovery. These results provide a promising strategy for developing a facile artificial olfactory system that demonstrates complicated biological synaptic functions with a seamless and simplified system architecture.

Risk Factors and Characteristics of In-Hospital Falls After Spine Surgery: A Retrospective, Single-Center Cohort Study in the Republic of Korea.

Background: Falls after orthopaedic surgery can cause serious injuries, which lengthen hospital stays and increase medical expenses. This has prompted hospitals to implement various fall-prevention protocols. The aims of this study were to determine the incidence of in-hospital falls after spine surgery, to analyze the overall risk factors, to discern factors that have a major influence on falls, and to evaluate the effectiveness of the fall-prevention protocol that we implemented. Methods: This was a retrospective, single-center study including patients who underwent spine surgery from January 2011 to November 2021 at the National Health Insurance Service Ilsan Hospital (NHISIH) in Goyang, Republic of Korea. Reported falls among these patients were examined. Patient demographics; surgery type, date, and diagnosis; and fall date and time were evaluated. Results: Overall, 5,317 spine surgeries were performed, and 128 in-hospital falls were reported (overall incidence: 2.31%). From the multivariable analyses, older age and American Society of Anesthesiologists (ASA) score were identified as independent risk factors for in-hospital patient falls (multivariable adjusted hazard ratio [aHR] for age 70 to 79 years, 1.021 [95% confidence interval (CI), 1.01 to 1.031]; for age ≥80 years, 1.035 [1.01 to 1.06]; and for ASA score of 3, 1.02 [1.01 to 1.031]). Similar results were seen in the subgroup who underwent primary surgery. Within 2 weeks following surgery, the highest frequency of falls occurred at 3 to 7 days postoperatively. The lowest fall rate was observed in the evening (6 to 10 p.m.). Morbidities, including rib, spine, and extremity fractures, were recorded for 14 patients, but none of these patients underwent operative treatment related to the fall. The NHISIH implemented a comprehensive nursing care service in May 2015 and a fall protocol in May 2017, but the annual incidence rate did not improve. The fall rate was higher after thoracolumbar surgeries (2.47%) than after cervical surgeries (1.20%). Moreover, a higher fall rate was observed in thoracolumbar cases with a greater number of fusion levels and revision spine surgeries. Conclusions: Patients with advanced age, more comorbidities, a greater number of fusion levels, and revision surgeries and who are female are more vulnerable to in-hospital falls after spine surgery. Novel strategies that target these risk factors are warranted. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Matrimeres are systemic nanoscale mediators of tissue integrity and function.

Tissue barriers must be rapidly restored after injury to promote regeneration. However, the mechanism behind this process is unclear, particularly in cases where the underlying extracellular matrix is still compromised. Here, we report the discovery of matrimeres as constitutive nanoscale mediators of tissue integrity and function. We define matrimeres as non-vesicular nanoparticles secreted by cells, distinguished by a primary composition comprising at least one matrix protein and DNA molecules serving as scaffolds. Mesenchymal stromal cells assemble matrimeres from fibronectin and DNA within acidic intracellular compartments. Drawing inspiration from this biological process, we have achieved the successful reconstitution of matrimeres without cells. This was accomplished by using purified matrix proteins, including fibronectin and vitronectin, and DNA molecules under optimal acidic pH conditions, guided by the heparin-binding domain and phosphate backbone, respectively. Plasma fibronectin matrimeres circulate in the blood at homeostasis but exhibit a 10-fold decrease during systemic inflammatory injury in vivo . Exogenous matrimeres rapidly restore vascular integrity by actively reannealing endothelial cells post-injury and remain persistent in the host tissue matrix. The scalable production of matrimeres holds promise as a biologically inspired platform for regenerative nanomedicine.

Missing methane emissions from urban sewer networks.

Methane emissions from sewer networks are an important source of anthropogenic greenhouse gases (GHGs) but are not currently reflected in the national GHG inventory. We found significant CH4 emissions of approximately 573 [395-831] CH4 t y-1 from sewer networks in the old residential and commercial areas of Seoul (Gwanak district) using an electric vehicle-based atmospheric GHG monitoring platform. The majority of ethane-to-methane ratios (<0.005) from the observations further suggest that distinctive CH4 emissions from sewer networks are likely related to microbial activity rather than to simple natural gas leakage. Because over 90% of the sewer network in Seoul is a gravity drain type of combined sewer network, where both wastewater and stormwater flow through the same pipes, resulting in the generation of methane emissions from the microbial activity and the manholes and rain gutters, which are directly connected to the combined sewer networks are major sources of atmospheric methane emissions. This study suggests that appropriate treatment of sewer networks can mitigate missing methane emissions in cities that were not originally included in GHG inventory of South Korea.

Effects of sudden shock load on simultaneous biohythane production in two-stage anerobic digestion of high-strength organic wastewater.

The two-stage anaerobic digestion (AD) for biohythane production is a sustainable solution, but it is sensitive to organic shock load that disrupts reactors and inhibits biohythane production. This study investigated biohythane production, reactor performance, and the possibility of post-failure restoration in a two-stage AD system designed for treating high-strength organic wastewater. Sudden shock load was applied by increasing the OLR threefold higher after reaching steady state phase. During shock load phase, hydrogen content, hydrogen yield and methane production rate (MPR) reached its peak values of 62.61 %, 1.641 mol H2/mol glucose, and 1.003 L CH4/L⋅d respectively before declining significantly. Interestingly, during the restorative phase, hydrogen production sharply declined to nearly zero, while methane production exhibited a resilience and reached its peak methane content of 52.2 %. The study successfully demonstrated the system's resilience to sudden shock load, ensuring stable methane production, while hydrogen production did not exhibit the same capability.

Towards single cell encapsulation for precision biology and medicine.

The primary impetus of therapeutic cell encapsulation in the past several decades has been to broaden the options for donor cell sources by countering against immune-mediated rejection. However, another significant advantage of encapsulation is to provide donor cells with physiologically relevant cues that become compromised in disease. The advances in biomaterial design have led to the fundamental insight that cells sense and respond to various signals encoded in materials, ranging from biochemical to mechanical cues. The biomaterial design for cell encapsulation is becoming more sophisticated in controlling specific aspects of cellular phenotypes and more precise down to the single cell level. This recent progress offers a paradigm shift by designing single cell-encapsulating materials with predefined cues to precisely control donor cells after transplantation.

Machine learning based estimation of urban on-road CO2 concentration in Seoul.

The urban on-road CO2 emissions will continue to increase, it is therefore essential to manage urban on-road CO2 concentrations for effective urban CO2 mitigation. However, limited observations of on-road CO2 concentrations prevents a full understanding of its variation. Therefore, in this study, a machine learning-based model that predicts on-road CO2 concentration (CO2traffic) was developed for Seoul, South Korea. This model predicts hourly CO2traffic with high precision (R2 = 0.8 and RMSE = 22.9 ppm) by utilizing CO2 observations, traffic volume, traffic speed, and wind speed as the main factors. High spatiotemporal inhomogeneity of hourly CO2traffic over Seoul, with 14.3 ppm by time-of-day and 345.1 ppm by road, was apparent in the CO2traffic data predicted by the model. The large spatiotemporal variability of CO2traffic was related to different road types (major arterial roads, minor arterial roads, and urban highways) and land-use types (residential, commercial, bare ground, and urban vegetation). The cause of the increase in CO2traffic differed by road type, and the diurnal variation of CO2traffic differed according to land-use type. Our results demonstrate that high spatiotemporal on-road CO2 monitoring is required to manage urban on-road CO2 concentrations with high variability. In addition, this study demonstrated that a model using machine learning techniques can be an alternative for monitoring CO2 concentrations on all roads without conducting observations. Applying the machine learning techniques developed in this study to cities around the world with limited observation infrastructure will enable effective urban on-road CO2 emissions management.

First quantification and chemical characterization of atmospheric microplastics observed in Seoul, South Korea.

This study is the first report on atmospheric microplastics (MPs) observed in five outdoor environments, including an urban forest, a business center, commercial areas, and a public transportation hub in Seoul, South Korea. Air samples were collected using an active air pump sampler for 24 h in each area only on days without rainfall. All observed microplastics are secondary microplastics, in the form of irregularly-shaped fragments or fibers produced through various degradation processes, rather than being primarily produced like microbeads. The abundance of atmospheric MPs varied depending on the environment (i.e., region, height, and time) from 0.33 to 1.21 MP m-3, with the average number of MPs being 0.72 MP m-3 (standard deviation ± 0.39). MPs in the urban forest was observed to be 27% lower in abundance than that in the urban center which is ∼3 km away. The central business district was observed to have a 25% higher abundance during weekdays than on weekends. Our results show the ubiquity of MPs in various areas from high-rise buildings to forests tens of kilometers away from their direct sources, and a positive correlation between the abundance of MP and human activity. Morphologically, the fragment type (87.4%) predominated over the fiber type (12.6%), and chemically, polypropylene (PP) and polyethylene terephthalate (PET) components accounted for 65% of the total MP. PP polymers were found in all observation sites and contributed to 59% of the total MP fragments. The observed fibrous MPs were mainly composed of PET (72.7%) and PP (18.2%) polymers. Compared to other large cities (Shanghai, Beijing, Paris), Seoul is exposed to low levels of atmospheric MPs and high proportions of PP polymers. This study is limited to atmospheric MPs observed in summer and further investigation of MPs is needed to comprehensively understand the distribution and cycle of MPs based on long-term monitoring of atmospheric MPs.

Development of a programmable magnetic agitation device to maintain colloidal suspension of cells during microfluidic syringe pump perfusion.

Droplet-based microfluidic devices have been used to achieve homogeneous cell encapsulation, but cells sediment in a solution, leading to heterogeneous products. In this technical note, we describe automated and programmable agitation device to maintain colloidal suspensions of cells. We demonstrate that the agitation device can be interfaced with a syringe pump for microfluidic applications. Agitation profiles of the device were predictable and corresponded to device settings. The device maintains the concentration of cells in an alginate solution over time without implicating cell viability. This device replaces manual agitation, and hence is suitable for applications that require slow perfusion for a longer period of time in a scalable manner.

Manipulation of the nucleoscaffold potentiates cellular reprogramming kinetics.

Somatic cell fate is an outcome set by the activities of specific transcription factors and the chromatin landscape and is maintained by gene silencing of alternate cell fates through physical interactions with the nuclear scaffold. Here, we evaluate the role of the nuclear scaffold as a guardian of cell fate in human fibroblasts by comparing the effects of transient loss (knockdown) and mutation (progeria) of functional Lamin A/C, a core component of the nuclear scaffold. We observed that Lamin A/C deficiency or mutation disrupts nuclear morphology, heterochromatin levels, and increases access to DNA in lamina-associated domains. Changes in Lamin A/C were also found to impact the mechanical properties of the nucleus when measured by a microfluidic cellular squeezing device. We also show that transient loss of Lamin A/C accelerates the kinetics of cellular reprogramming to pluripotency through opening of previously silenced heterochromatin domains while genetic mutation of Lamin A/C into progerin induces a senescent phenotype that inhibits the induction of reprogramming genes. Our results highlight the physical role of the nuclear scaffold in safeguarding cellular fate.

Programming of Multicellular Patterning with Mechano-Chemically Microstructured Cell Niches.

Multicellular patterning of stem-cell-derived tissue models is commonly achieved via self-organizing activities triggered by exogenous morphogenetic stimuli. However, such tissue models are prone to stochastic behavior, limiting the reproducibility of cellular composition and forming non-physiological architectures. To enhance multicellular patterning in stem cell-derived tissues, a method for creating complex tissue microenvironments endowed with programmable multimodal mechano-chemical cues, including conjugated peptides, proteins, morphogens, and Young's moduli defined over a range of stiffnesses is developed. The ability of these cues to spatially guide tissue patterning processes, including mechanosensing and the biochemically driven differentiation of selected cell types, is demonstrated. By rationally designing niches, the authors engineered a bone-fat assembly from stromal mesenchyme cells and regionalized germ layer tissues from pluripotent stem cells. Through defined niche-material interactions, mechano-chemically microstructured niches enable the spatial programming of tissue patterning processes. Mechano-chemically microstructured cell niches thereby offer an entry point for enhancing the organization and composition of engineered tissues, potentiating structures that better recapitulate their native counterparts.

Subdural hygroma as a rare complication after revision spine surgery.

Spinal fusion surgery is the most commonly performed orthopaedic surgical procedure. However, subdural hygroma occurrence is a very rare complication after revision spinal fusion surgery. Here, we report a case of revision lumbar fusion surgery at the L3-4 level. The patient developed acute conus medullaris syndrome at 10 days postoperatively. MRI showed a subdural, extra-arachnoid area fluid collection following the T12-L2, cephalad to the area of revision spinal fusion. When patients have a decreased motor grade, difficulty in voiding urine and neurological abnormalities after lumbar spine surgery, conus medullaris syndrome with a possible occurrence of subdural hygroma should be considered. In this situation, immediate imaging investigations and emergency surgery might be necessary to reduce the pressure on the spinal cord.

Deterministic Single Cell Encapsulation in Asymmetric Microenvironments to Direct Cell Polarity.

Various signals in tissue microenvironments are often unevenly distributed around cells. Cellular responses to asymmetric cell-matrix adhesion in a 3D space remain generally unclear and are to be studied at the single-cell resolution. Here, the authors developed a droplet-based microfluidic approach to manufacture a pure population of single cells in a microscale layer of compartmentalized 3D hydrogel matrices with a tunable spatial presentation of ligands at the subcellular level. Cells elongate with an asymmetric presentation of the integrin adhesion ligand Arg-Gly-Asp (RGD), while cells expand isotropically with a symmetric presentation of RGD. Membrane tension is higher on the side of single cells interacting with RGD than on the side without RGD. Finite element analysis shows that a non-uniform isotropic cell volume expansion model is sufficient to recapitulate the experimental results. At a longer timescale, asymmetric ligand presentation commits mesenchymal stem cells to the osteogenic lineage. Cdc42 is an essential mediator of cell polarization and lineage specification in response to asymmetric cell-matrix adhesion. This study highlights the utility of precisely controlling 3D ligand presentation around single cells to direct cell polarity for regenerative engineering and medicine.

Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.

Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more "patient specific" screening tools either in the guise of 3D matrix models, microphysiological "organ-on-chip" tools or xenograft models and discuss representative examples.

Extracellular vesicle-matrix interactions.

The extracellular matrix in microenvironments harbors a variety of signals to control cellular functions and the materiality of tissues. Most efforts to synthetically reconstitute the matrix by biomaterial design have focused on decoupling cell-secreted and polymer-based cues. Cells package molecules into nanoscale lipid membrane-bound extracellular vesicles and secrete them. Thus, extracellular vesicles inherently interact with the meshwork of the extracellular matrix. In this Review, we discuss various aspects of extracellular vesicle-matrix interactions. Cells receive feedback from the extracellular matrix and leverage intracellular processes to control the biogenesis of extracellular vesicles. Once secreted, various biomolecular and biophysical factors determine whether extracellular vesicles are locally incorporated into the matrix or transported out of the matrix to be taken up by other cells or deposited into tissues at a distal location. These insights can be utilized to develop engineered biomaterials where EV release and retention can be precisely controlled in host tissue to elicit various biological and therapeutic outcomes.