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.

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.

MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF-κB Translocation in T24 Bladder Cancer Cells.

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.

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.

Mercaptoamine-assisted Post-encapsulation of Metal Nanoparticles within Preformed Zeolites and their Analogues for Hydroisomerization and Methane Decomposition.

We report a general synthetic strategy for post-encapsulation of metal nanoparticles within preformed zeolites using post-synthetic modification. Both anionic and cationic precursors to metal nanoparticle are supported on 8- and 10-membered ring zeolites and analogues during wet impregnation using 2-aminoethanethiol (AET) as a bi-grafting agent. Thiol groups are coordinated to metal centers, whereas amine moieties are dynamically attached to micropore walls via acid-base interactions. The dynamic acid-base interactions cause the even distribution of the metal-AET complex throughout the zeolite matrix. These processes encapsulate Au, Rh, and Ni precursors within the CHA, *MRE, MFI zeolite, and SAPO-34 zeolite analogues, for which small channel apertures preclude the post-synthesis impregnation of metal precursors. Sequential activation forms small and uniform nanoparticles (1-2.5 nm in diameter), as confirmed through electron microscopy and X-ray absorption spectroscopy. Containment within the small micropores protected the nanoparticles against harsh thermal sintering conditions and prevented the fouling of the metal surface by coke, thus resulting in a high catalytic performance in n-dodecane hydroisomerization and methane decomposition. The remarkable specificity of the thiol to metal precursors and the dynamic acid-base interaction make these protocols extendable to various metal-zeolite systems, suitable for shape-selective catalysts in challenging chemical environments.

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.

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.

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.

Changes in retro-odontoid mass after upper cervical spine surgery.

A non-neoplastic mass posterior to the dens is termed a retro-odontoid mass (R-OM). This retrospective study evaluated radiographic and clinical outcomes and R-OM changes after upper cervical spine surgery. This study included 69 patients who underwent upper cervical spine surgery, including atlantoaxial fusion, occipitocervical fusion, or decompression. All patients underwent preoperative magnetic resonance imaging (MRI). Six-month follow-up MRI examinations were performed in 30 patients who had preoperative R-OMs. Radiographic outcomes of the anterior and posterior atlantodental intervals were measured using X-rays and computed tomography. The R-OM and space available for the cord (SAC) were measured using MRI. Clinical outcomes were evaluated using neck and arm pain visual analog scales, the Japanese Orthopedic Association score, the neck disability index, and the patient-reported subjective improvement rate. The anterior atlantodental interval decreased, while the posterior atlantodental interval and SAC increased postoperatively. Among the clinical outcomes, the neck and arm pain and the neck disability index decreased postoperatively, while the Japanese Orthopedic Association score increased. All clinical and radiographic outcomes improved postoperatively. The R-OM either decreased in size or disappeared after fusion surgery in all cases, except in one patient who underwent decompression surgery. In conclusion, stabilization through fusion surgery is essential for treating R-OM.

Comparison of the efficacy between sequential therapy with teriparatide and denosumab and denosumab monotherapy in suppressing fragility fracture risk.

In this retrospective study, the effectiveness of short-term teriparatide with denosumab in reducing fragility fracture risk was determined in comparison with denosumab monotherapy. Administration of sequential teriparatide with denosumab showed excellent outcomes in suppressing the risk for fragility fractures compared with denosumab monotherapy. INTRODUCTION: To determine the effectiveness of short-term teriparatide with denosumab in reducing the risk of fragility fractures in comparison to denosumab monotherapy. METHODS: The data of postmenopausal patients treated with denosumab for > 2 years between August 2015 and October 2020 were retrospectively analyzed. One hundred sixty four postmenopausal women of a total 615 were excluded, since they did not undergo > 2 bone mineral density (BMD) tests, were lost to follow-up, or received long-term teriparatide therapy. Total 320 patients received denosumab monotherapy and 131 patients received teriparatide for ≥ 3 months followed by denosumab. The number of osteoporotic fractures, presence of back pain before and after treatment, and annual BMD during treatment were comparatively assessed using t-test, Chi-square test, and linear mixed model analysis. RESULTS: Before treatment, the denosumab monotherapy group had fewer osteoporotic fractures (mean ± standard deviation; 0.459 ± 0.689) than the sequential therapy group had (1.037 ± 0.871; p < 0.001). After treatment, the sequential therapy group had fewer osteoporotic fractures than the denosumab monotherapy group had (0.119 ± 0.348 versus 0.144 ± 0.385; p < 0.001). At 1 and 2 years after treatment, the increase in lumbar spine BMD was greater in the sequential therapy group than in the denosumab monotherapy group (p = 0.08, group × time). The difference between post and pre-treatment back pain visual analog scale score was significantly lower in the sequential therapy group than in the monotherapy group (3.246 ± 3.426 versus 1.734 ± 3.049; p < 0.001). CONCLUSION: Short-term teriparatide use before denosumab showed excellent outcomes in suppressing the risk of fragility fractures compared with denosumab monotherapy.

Nanoparticle targeting of de novo profibrotic macrophages mitigates lung fibrosis.

The pathogenesis of lung fibrosis involves hyperactivation of innate and adaptive immune pathways that release inflammatory cytokines and growth factors such as tumor growth factor (TGF)ß1 and induce aberrant extracellular matrix protein production. During the genesis of pulmonary fibrosis, resident alveolar macrophages are replaced by a population of newly arrived monocyte-derived interstitial macrophages that subsequently transition into alveolar macrophages (Mo-AMs). These transitioning cells initiate fibrosis by releasing profibrotic cytokines and remodeling the matrix. Here, we describe a strategy for leveraging the up-regulation of the mannose receptor CD206 in interstitial macrophages and Mo-AM to treat lung fibrosis. We engineered mannosylated albumin nanoparticles, which were found to be internalized by fibrogenic CD206+ monocyte derived macrophages (Mo-Macs). Mannosylated albumin nanoparticles incorporating TGFß1 small-interfering RNA (siRNA) targeted the profibrotic subpopulation of CD206+ macrophages and prevented lung fibrosis. The findings point to the potential utility of mannosylated albumin nanoparticles in delivering TGFß-siRNA into CD206+ profibrotic macrophages as an antilung fibrosis strategy.

Direct Internal Fixation for Unstable Atlas Fractures.

PURPOSE: To investigate the radiologic and clinical outcomes of direct internal fixation for unstable atlas fractures. MATERIALS AND METHODS: This retrospective study included 12 patients with unstable atlas fractures surgically treated using C1 lateral mass screws, rods, and transverse connector constructs. Nine lateral mass fractures with transverse atlantal ligament (TAL) avulsion injury and three 4-part fractures with TAL injury (two avulsion injuries, one TAL substance tear) were treated. Radiologic outcomes included the anterior atlantodental interval (AADI) in flexion and extension cervical spine lateral radiographs at 6 months and 1 year after treatment. CT was also performed to visualize bony healing of the atlas at 6 months and 1 year. Visual Analog Scale (VAS) scores for neck pain, Neck Disability Index (NDI) values, and cervical range of motion (flexion, extension, and rotation) were recorded at 6 months after surgery. RESULTS: The mean postoperative extension and flexion AADIs were 3.79±1.56 (mean±SD) and 3.13±1.01 mm, respectively. Then mean AADI was 3.42±1.34 and 3.33±1.24 mm at 6 months and 1 year after surgery, respectively. At 1 year after surgery, 11 patients showed bony healing of the atlas on CT images. Only one patient underwent revision surgery 8 months after primary surgery due to nonunion and instability findings. The mean VAS score for neck pain was 0.92±0.99, and the mean NDI value was 8.08±5.70. CONCLUSION: C1 motion-preserving direct internal fixation technique results in good reduction and stabilization of unstable atlas fractures. This technique allows for the preservation of craniocervical and atlantoaxial motion.

Inhibition of aberrant tissue remodelling by mesenchymal stromal cells singly coated with soft gels presenting defined chemomechanical cues.

The precise understanding and control of microenvironmental cues could be used to optimize the efficacy of cell therapeutics. Here, we show that mesenchymal stromal cells (MSCs) singly coated with a soft conformal gel presenting defined chemomechanical cues promote matrix remodelling by secreting soluble interstitial collagenases in response to the presence of tumour necrosis factor alpha (TNF-α). In mice with fibrotic lung injury, treatment with the coated MSCs maintained normal collagen levels, fibre density and microelasticity in lung tissue, and the continuous presentation of recombinant TNF-α in the gel facilitated the reversal of aberrant tissue remodelling by the cells when inflammation subsided in the host. Gel coatings with predefined chemomechanical cues could be used to tailor cells with specific mechanisms of action for desired therapeutic outcomes.

Cell-Matrix Interactions Regulate Functional Extracellular Vesicle Secretion from Mesenchymal Stromal Cells.

Extracellular vesicles (EVs) are cell-secreted particles with broad potential to treat tissue injuries by delivering cargo to program target cells. However, improving the yield of functional EVs on a per cell basis remains challenging due to an incomplete understanding of how microenvironmental cues regulate EV secretion at the nanoscale. We show that mesenchymal stromal cells (MSCs) seeded on engineered hydrogels that mimic the elasticity of soft tissues with a lower integrin ligand density secrete ∼10-fold more EVs per cell than MSCs seeded on a rigid plastic substrate, without compromising their therapeutic activity or cargo to resolve acute lung injury in mice. Mechanistically, intracellular CD63+ multivesicular bodies (MVBs) transport faster within MSCs on softer hydrogels, leading to an increased frequency of MVB fusion with the plasma membrane to secrete more EVs. Actin-related protein 2/3 complex but not myosin-II limits MVB transport and EV secretion from MSCs on hydrogels. The results provide a rational basis for biomaterial design to improve EV secretion while maintaining their functionality.

Direct comparison of angiogenesis in natural and synthetic biomaterials reveals that matrix porosity regulates endothelial cell invasion speed and sprout diameter.

Vascularization of large, diffusion-hindered biomaterial implants requires an understanding of how extracellular matrix (ECM) properties regulate angiogenesis. Sundry biomaterials assessed across many disparate angiogenesis assays have highlighted ECM determinants that influence this complex multicellular process. However, the abundance of material platforms, each with unique parameters to model endothelial cell (EC) sprouting presents additional challenges of interpretation and comparison between studies. In this work we directly compared the angiogenic potential of commonly utilized natural (collagen and fibrin) and synthetic dextran vinyl sulfone (DexVS) hydrogels in a multiplexed angiogenesis-on-a-chip platform. Modulating matrix density of collagen and fibrin hydrogels confirmed prior findings that increases in matrix density correspond to increased EC invasion as connected, multicellular sprouts, but with decreased invasion speeds. Angiogenesis in synthetic DexVS hydrogels, however, resulted in fewer multicellular sprouts. Characterizing hydrogel Young's modulus and permeability (a measure of matrix porosity), we identified matrix permeability to significantly correlate with EC invasion depth and sprout diameter. Although microporous collagen and fibrin hydrogels produced lumenized sprouts in vitro, they rapidly resorbed post-implantation into the murine epididymal fat pad. In contrast, DexVS hydrogels proved comparatively stable. To enhance angiogenesis within DexVS hydrogels, we incorporated sacrificial microgels to generate cell-scale pores throughout the hydrogel. Microporous DexVS hydrogels resulted in lumenized sprouts in vitro and enhanced cell invasion in vivo. Towards the design of vascularized biomaterials for long-term regenerative therapies, this work suggests that synthetic biomaterials offer improved size and shape control following implantation and that tuning matrix porosity may better support host angiogenesis. STATEMENT OF SIGNIFICANCE: Understanding how extracellular matrix properties govern angiogenesis will inform biomaterial design for engineering vascularized implantable grafts. Here, we utilized a multiplexed angiogenesis-on-a-chip platform to compare the angiogenic potential of natural (collagen and fibrin) and synthetic dextran vinyl sulfone (DexVS) hydrogels. Characterization of matrix properties and sprout morphometrics across these materials points to matrix porosity as a critical regulator of sprout invasion speed and diameter, supported by the observation that nanoporous DexVS hydrogels yielded endothelial cell sprouts that were not perfusable. To enhance angiogenesis into synthetic hydrogels, we incorporated sacrificial microgels to generate microporosity. We find that microporosity increased sprout diameter in vitro and cell invasion in vivo. This work establishes a composite materials approach to enhance the vascularization of synthetic hydrogels.