Contrast-enhanced US in Renal Transplant Complications: Overview and Imaging Features.

Renal transplant is the first-line treatment of end-stage renal disease. The increasing number of transplants performed every year has led to a larger population of transplant patients. Complications may arise during the perioperative and postoperative periods, and imaging plays a key role in this scenario. Contrast-enhanced US (CEUS) is a safe tool that adds additional value to US. Contrast agents are usually administered intravenously, but urinary tract anatomy and complications such as stenosis or leak can be studied using intracavitary administration of contrast agents. Assessment of the graft and iliac vessels with CEUS is particularly helpful in identifying vascular and parenchymal complications, such as arterial or venous thrombosis and stenosis, acute tubular injury, or cortical necrosis, which can lead to graft loss. Furthermore, infectious and malignant graft involvement can be accurately studied with CEUS, which can help in detection of renal abscesses and in the differentiation between benign and malignant disease. CEUS is also useful in interventional procedures, helping to guide percutaneous aspiration of collections with better delimitation of the graft boundaries and to guide renal graft biopsies by avoiding avascular areas. Potential postprocedural vascular complications, such as pseudoaneurysm, arteriovenous fistula, or active bleeding, are identified with CEUS. In addition, newer quantification tools such as CEUS perfusion are promising, but further studies are needed to approve its use for clinical purposes. ©RSNA, 2024 Supplemental material is available for this article.

Malnutrition and sarcopenia worsen short- and long-term outcomes in internal medicine inpatients.

PURPOSE: This work aims to describe patients hospitalized in internal medicine wards in terms of nutrition and sarcopenia. It also seeks to evaluate short- and long-term mortality related to malnutrition and sarcopenia. METHODS: This cross-sectional study collected data on consecutive patients admitted to a single center's internal medicine ward. Patients were recruited in May and October 2021. Malnutrition was determined by the Mini-Nutritional Assessment-Short Form (MNA-SF) and sarcopenia by the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls questionnaire (SARC-F scale) and handgrip strength test. Patients who were hospitalized for >48 hours were excluded. RESULTS: The sample included 619 patients with a mean ± SD age of 76.0 ± 14.8 years of which 50.6% were women. Patients were classified into three groups based on malnutrition: group 1 (MNA-SF 12-14 points) (no risk) included 158 patients, group 2 (MNA-SF 8-12 points) (high risk) included 233 patients, and group 3 (MNA-SF 0-7 points) (malnourished) included 228 patients. Malnourished patients had more dysphagia, significantly lower protein and albumin levels, and significantly higher inflammatory marker levels and pressure ulcers. In-hospital mortality was significantly higher in groups 2 and 3 (p < .00001). The worst outcome (mortality and readmissions or mortality) was more common among malnourished patients (p = .0001). Inflammation, comorbidity, and sarcopenia were most closely associated with negative outcomes. CONCLUSION: Malnutrition upon admission is associated with worse short- and long-term outcomes in internal medicine inpatients. Sarcopenia, multimorbidity, and inflammation-measured by albumin, C-reactive protein, or their ratios-are key risk factors. Early identification of malnutrition and sarcopenia through active screening is important in caring for internal medicine patients.

Kinematic analysis of sensorimotor control during the craniocervical flexion movement in patients with neck pain and asymptomatic individuals: a cross-sectional study.

BACKGROUND: Patients with craniocervical pain have shown reduced performance in the craniocervical flexion test (CCFT). However, there is limited evidence of other possible kinematic alterations not assessed in the context of the CCFT. Previous studies on other functional or planar movements have reported alterations in sensorimotor control (e.g., range of motion [ROM], velocity, or smoothness) in subjects with neck pain. The objective of this study was to explore the association between sensorimotor control variables associated with craniocervical flexion movement and different characteristics related to pain, age, disability, and fear of movement in individuals with non-traumatic chronic neck pain and asymptomatic controls. METHODS: This was an observational, cross-sectional study in patients with non-traumatic neck pain and asymptomatic participants. Regression models were used to assess whether descriptive characteristics of the sample, including: (a) age, (b) intensity of pain, (c) neck disability, (d) chronicity of pain, and (e) fear of movement could explain sensorimotor control variables such as ROM, velocity, jerk, head repositioning accuracy, and conjunct motion. All these variables were recorded by means of light inertial measurement unit sensors during the performance of three maximal repetitions of full range craniocervical flexion in the supine position. RESULTS: A total of 211 individuals were screened and 192 participants finished the protocol and were included in the analyses. Participants had an average age of 34.55 ± 13.93 years and included 124 patients with non-traumatic neck pain and 68 asymptomatic subjects. Kinesiophobia partially explained lower craniocervical flexion ROM (p = .01) and lower peak velocity in flexion (P < .001). Age partially explained increased craniocervical extension ROM (P < .001) and lower peak velocity in flexion (P = .03). Chronicity partially explained increased lateral flexion conjunct motion (P = .008). All models showed low values of explained variance (< 32%) and low absolute values of regression coefficients. CONCLUSIONS: This study did not find a clear relationship between population characteristics and sensorimotor control variables associated with the craniocervical flexion movement. Kinesiophobia might have some association with reduced ROM in craniocervical flexion, but further research in this field is needed in large samples of patients with higher levels of kinesiophobia pain or disability.

Potential Use of Wearable Inertial Sensors to Assess and Train Deep Cervical Flexors: A Feasibility Study with Real Time Synchronization of Kinematic and Pressure Data during the Craniocervical Flexion Test.

The aim of the study was to develop a novel real-time, computer-based synchronization system to continuously record pressure and craniocervical flexion ROM (range of motion) during the CCFT (craniocervical flexion test) in order to assess its feasibility for measuring and discriminating the values of ROM between different pressure levels. This was a descriptive, observational, cross-sectional, feasibility study. Participants performed a full-range craniocervical flexion and the CCFT. During the CCFT, a pressure sensor and a wireless inertial sensor simultaneously registered data of pressure and ROM. A web application was developed using HTML and NodeJS technologies. Forty-five participants successfully finished the study protocol (20 males, 25 females; 32 (11.48) years). ANOVAs showed large effect significant interactions between pressure levels and the percentage of full craniocervical flexion ROM when considering the 6 pressure reference levels of the CCFT (p < 0.001; η2 = 0.697), 11 pressure levels separated by 1 mmHg (p < 0.001; η2 = 0.683), and 21 pressure levels separated by 0.5 mmHg (p < 0.001; η2 = 0.671). The novel time synchronizing system seems a feasible option to provide real-time monitoring of both pressure and ROM, which could serve as reference targets to further investigate the potential use of inertial sensor technology to assess or train deep cervical flexors.

In Vitro Evaluation of Antioxidant Potential of the Invasive Seagrass Halophila stipulacea.

Marine organisms with fast growth rates and great biological adaptive capacity might have biotechnological interests, since ecological competitiveness might rely on enhanced physiological or biochemical processes' capability promoting protection, defense, or repair intracellular damages. The invasive seagrass Halophila stipulacea, a non-indigenous species widespread in the Mediterranean Sea, belongs to this category. This is the premise to investigate the biotechnological interest of this species. In this study, we investigated the antioxidant activity in vitro, both in scavenging reactive oxygen species and in repairing damages from oxidative stress on the fibroblast human cell line WI-38. Together with the biochemical analysis, the antioxidant activity was characterized by the study of the expression of oxidative stress gene in WI-38 cells in presence or absence of the H. stipulacea extract. Concomitantly, the pigment pool of the extracts, as well as their macromolecular composition was characterized. This study was done separately on mature and young leaves. Results indicated that mature leaves exerted a great activity in scavenging reactive oxygen species and repairing damages from oxidative stress in the WI-38 cell line. This activity was paralleled to an enhanced carotenoids content in the mature leaf extracts and a higher carbohydrate contribution to organic matter. Our results suggest a potential of the old leaves of H. stipulacea as oxidative stress damage protecting or repair agents in fibroblast cell lines. This study paves the way to transmute the invasive H. stipulacea environmental threat in goods for human health.

Anterior and distal tunnel orientation for anatomic reconstruction of the medial patellofemoral ligament is safer in patients with open growth plates.

PURPOSE: In patients with open growth plates, the direction of tunneling that avoids distal femoral physis (DFP) damage in anatomic reconstructions of the medial patellofemoral ligament (MPFL) has been a topic of discussion. The objective of this study was to determine the ideal orientation for anatomic reconstructions of MPFL tunneling that minimized DFP damage while avoiding breaching the intercondylar notch. METHODS: Eighty magnetic resonance images of patients aged 10 through 17 were obtained, randomly sampled from the institutional database. A de novo software was developed to obtain 3D models of the distal femur and DFP. In each model, the anatomical insertion point of the MPFL was determined as defined by Stephen. A 20-mm-depth drilling was simulated, starting from the insertion point at every possible angle within a 90° cone using 5-, 6- and 7-mm drills. Physeal damage for each pair of angles and each drill size was determined. Damage was expressed as a percentage of total physis volume. Statistical analysis was conducted using Student's t test and one-way ANOVA. RESULTS: Maximum physeal damage (5.35% [4.47-6.24]) was obtained with the 7-mm drill when drilling 3° cephalic and 15° posterior from insertion without differences between sexes (n.s.). Minimal physeal damage (0.22% [0.07-0.37]) was obtained using the 5-mm drill aimed 45° distal and 0° anteroposterior, not affected by sex (n.s.). Considering intra-articular drilling avoidance, the safest zone was obtained when aiming 30°-40° distal and 5°-35° anterior, regardless of sex. CONCLUSION: Ideal femoral tunnel orientation, avoiding physeal damage and breaching of the intercondylar notch, was obtained when aiming 30°-40° distal and 5°-35° anterior, regardless of sex. This area is a safe zone that allows anatomic MPFL reconstruction of patients with an open physis.

Analysis of the Microbiota of the Physiotherapist's Environment.

OBJECTIVES: To analyze the microbiota of the physiotherapist's work environment to understand the existing potential risks and to adopt appropriate preventive measures. DESIGN: Cross-sectional descriptive observational study. SETTING: Physiotherapist's working environment. PARTICIPANTS: Physiotherapy and rehabilitation centers (N=19). INTERVENTIONS: A microbiological sampling was carried out in the physiotherapy centers. The samples were studied using the usual culture and analysis methodology for characterization and isolation of a range of bacteria. MAIN OUTCOME MEASURES: Absolute and relative frequency of microorganism isolation. RESULTS: In the analysis, pathogens normally responsible for nosocomial infections were detected, especially on instruments and equipment used by the physiotherapist such as sponge electrodes, and were significantly more contaminated than the rest of the places studied (P<.01). CONCLUSION: This situation confirms the absence of measures and protocols for the prevention and control of such infections in the physiotherapist's environment, which is why they must be considered to protect both physiotherapy professionals and patients.

A novel use of inertial sensors to measure the craniocervical flexion range of motion associated to the craniocervical flexion test: an observational study.

BACKGROUND: The craniocervical flexion test (CCFT) is recommended when examining patients with neck pain related conditions and as a deep cervical retraining exercise option. During the execution of the CCFT the examiner should visually assess that the amount of craniocervical flexion range of motion (ROM) progressively increases. However, this task is very subjective. The use of inertial wearable sensors may be a user-friendly option to measure and objectively monitor the ROM. The objectives of our study were (1) to measure craniocervical flexion range of motion (ROM) associated with each stage of the CCFT using a wearable inertial sensor and to determine the reliability of the measurements and (2) to determine craniocervical flexion ROM targets associated with each stage of the CCFT to standardize their use for assessment and training of the deep cervical flexor (DCF) muscles. METHODS: Adults from a university community able to successfully perform the CCFT participated in this study. Two independent examiners evaluated the CCFT in two separate sessions. During the CCFT, a small wireless inertial sensor was adhered to the centre of the forehead to provide real-time monitoring and to record craniocervical flexion ROM. The intra- and inter-rater reliability of the assessment of craniocervical ROM was calculated. This study was approved by the Research Ethics Committee of CEU San Pablo University (236/17/08). RESULTS: Fifty-six participants (18 males, 23 females; mean [SD] age, 21.8 [3.45] years) were included in the study and successfully completed the study protocol. All interclass correlation coefficient (ICC) values indicated good or excellent reliability of the assessment of craniocervical ROM using a wearable inertial sensor. There was high variability between subjects on the amount of craniocervical ROM necessary to achieve each stage of the CCFT. CONCLUSIONS: The use of inertial sensors is a reliable method to measure the craniocervical flexion ROM associated with the CCFT. The great variability in the ROM limits the possibility to standardize a set of targets of craniocervical flexion ROM equivalent to each of the pressure targets of the pressure biofeedback unit.

Food Modulation Controls Astaxanthin Accumulation in Eggs of the Sea Urchin Arbacia lixula.

The carotenoid astaxanthin has strong antioxidant properties with beneficial effects for various degenerative diseases. This carotenoid is produced by some microalgae species when cultivated in particular conditions, and, interestingly, it is a predominant carotenoid in aquatic animals throughout a broad range of taxa. Recently, astaxanthin was detected in the eggs of the sea urchin Arbacia lixula in relevant concentrations when this organism was maintained in culture. These results have paved the way for deeper research into astaxanthin production by this species, particularly in regards to how astaxanthin production can be modulated by diet. Results showed that the highest content of astaxanthin in eggs was observed in sea urchins fed on a diet enriched with Spirulina platensis. This result was confirmed by the high antioxidant activity recorded in the egg extracts of these animals. Our results suggest that (i) the sea urchin A. lixula is able to synthesize astaxanthin from precursors obtained from food, and (ii) it is possible to modulate the astaxanthin accumulation in sea urchin eggs by modifying the proportions of different food ingredients provided in their diet. This study demonstrates the large potential of sea urchin cultivation for the eco-sustainable production of healthy supplements for nutraceutical applications.

Kleptopredation: a mechanism to facilitate planktivory in a benthic mollusc.

Predation occurs when an organism completely or partially consumes its prey. Partial consumption is typical of herbivores but is also common in some marine microbenthic carnivores that feed on colonial organisms. Associations between nudibranch molluscs and colonial hydroids have long been assumed to be simple predator-prey relationships. Here we show that while the aeolid nudibranch Cratena peregrina does prey directly on the hydranths of Eudendrium racemosum, it is stimulated to feed when hydranths have captured and are handling prey, thus ingesting recently captured plankton along with the hydroid polyp such that plankton form at least half of the nudibranch diet. The nudibranch is thus largely planktivorous, facilitated by use of the hydroid for prey capture. At the scale of the colony this combines predation with kleptoparasitism, a type of competition that involves the theft of already-procured items to form a feeding mode that does not fit into existing classifications, which we term kleptopredation. This strategy of subsidized predation helps explain how obligate-feeding nudibranchs obtain sufficient energy for reproduction from an ephemeral food source.

The Sea Urchin Arbacia lixula: A Novel Natural Source of Astaxanthin.

Several echinoderms, including sea urchins, are valuable sources of bioactive compounds but their nutraceutical potential is largely unexplored. In fact, the gonads of some sea urchin species contain antioxidants including carotenoids and polyhydroxylated naphthoquinones (PHNQ's), such as echinochrome A. Astaxanthin is known to have particular bioactivity for the prevention of neurodegenerative diseases. This carotenoid is produced by microalgae, while several marine invertebrates can bioaccumulate or synthetize it from metabolic precursors. We determined the carotenoid content and analyzed the bioactivity potential of non-harvested Atlantic-Mediterranean sea urchin Arbacia lixula. The comparison of methanol crude extracts obtained from eggs of farmed and wild specimens revealed a higher bioactivity in farmed individuals fed with a customized fodder. HPLC-analysis revealed a high concentration of astaxanthin (27.0 µg/mg), which was the only pigment observed. This study highlights the potential of farmed A. lixula as a new source of the active stereoisomer of astaxanthin.

Spatial management of fisheries in the mediterranean sea: problematic issues and a few success stories.

Fishing has been important in the Mediterranean region for many centuries and still has a central role in its economic importance and cultural heritage. A multitude of fishery-oriented marine managed areas have been implemented under a highly complex political and legislative framework to protect fishery resources and sensitive habitats from high impact uses. However, a review of the literature revealed that few data are available to support their effectiveness, except for a few studies on fishery reserves and marine reserves. In these cases, fish biomass has increased and some evidence of ecological and socioeconomic benefits has been documented. The environmental and geopolitical complexity of the Mediterranean region as well as the dominant top-down management approaches, constitute the weakest points in the spatial management of fisheries at regional level. A coordinating role of all national and supranational bodies present in the area is desirable in the near future.

Periodicity of Ascaridia galli egg excretion in experimentally infected chicken in the Philippines.

The periodicity of parasite egg excretion refers to variations in the number of eggs produced across time, with significant implications in optimizing diagnostic procedures and conducting the Fecal Egg Count Reduction Test (FECRT). Here, we explore whether Ascaridia galli egg excretion varies across time under Philippine conditions, thus informing the best time to collect fecal samples during flock health examination. A time-course analysis was performed in chickens (N = 12) experimentally infected with A. galli, isolated from a naturally infected Philippine native chicken. We examined the fecal egg per gram (EPG) count at 3-h intervals for 3 days, starting from 5:00-6:00 h AM to the following day at 1:00-2:00 h AM. Our results showed a consistent daily egg excretion pattern with a peak EPG count in the morning that abruptly declined in the afternoon and lowest in the evening. The EPG counts correlated with the amount of excreta produced, suggesting that A. galli fecundity corresponds to the timing of host defecation. Our results imply that the best time to collect fecal samples for A. galli diagnosis and FECRT in Philippine conditions should be from sunrise until late morning when parasite EPG count and host excreta production are at their highest.

Tibial tubercle to trochlear groove and the roman arch method for tibial tubercle lateralisation are reliable and distinguish between subjects with and without major patellar instability.

PURPOSE: Patellofemoral (PF) instability recurrence depends on several factors including the relative lateralisation of tibial tubercle (TT) regarding the trochlear groove (TG). TT relative lateralisation quantification has long been a topic of debate. Multiple measuring techniques have been described including TT-trochlear groove (TT-TG), TT-posterior cruciate ligament (TT-PCL) and TT-roman arch (TT-RA), with no clear consensus regarding the most reliable index or pathologic threshold. We set out to determine the normal value range of each index and their association with age, sex and PF instability status. Also, this study aims to determine a reliable pathologic distance threshold to effectively predict patellar dislocation. METHODS: Skeletally mature patients up to 45 years of age who presented a CT Scan and an MRI of the same knee between 2014 and 2018 were included and divided into subgroups based on history of PF instability. Three indexes (TT-TG, TT-PCL and TT-RA) were assessed by two independent observers blinded to instability history. ROC curves were performed for each index to obtain the cut point that better predicts instability. Univariate and multivariate models adjusted by age, sex, instability history and type of imaging technique were performed to test the influence of these variables. RESULTS: 208 patients were included. Mean age was 27.93 â€‹± â€‹8.48 years, 67.3% were female and 71 patients (34.1%) presented major instability history. Good or excellent inter and intraobserver reliability was found for all three indexes. All indexes presented significantly different distributions between subjects with and without major instability (p â€‹< â€‹0.001), except for TT-PCL. Different cut point values differing between imaging modalities were found: 11.4 â€‹mm for MRI TT-TG, 17 â€‹mm for CT TT-TG, 15.6 â€‹mm for MRI TT-RA and 18.2 â€‹mm for CT TT-RA. CONCLUSIONS: All indexes studied had good or excellent inter and intraobserver reliability. Measurements between imaging techniques (CT and MR) are not interchangeable. Both TT-TG and TT-RA correctly distinguish between subjects with and without major instability, while TT-PCL does not, recommending caution when evaluated on its own. Specific threshold values depending on imaging technique should be considered for surgical decision-making. LEVEL OF EVIDENCE: Level IV, Diagnostic Test.

Reduction of small-prey capture rate and collective predation in the bleached sea anemone Exaiptasiadiaphana.

Cnidarians may dominate benthic communities, as in the case of coral reefs that foster biodiversity and provide important ecosystem services. Polyps may feed by predating mesozooplantkon and large motile prey, but many species further obtain autotrophic nutrients from photosymbiosis. Anthropogenic disturbance, such as the rise of seawater temperature and turbidity, can lead to the loss of symbionts, causing bleaching. Prolonged periods of bleaching can induce mortality events over vast areas. Heterotrophy may allow bleached cnidarians to survive for long periods of time. We tested the reinforcement of heterotrophic feeding of bleached polyps of Exaiptasia diaphana fed with both small zooplantkon and large prey, in order to evaluate if heterotrophy allows this species to compensate the reduction of autotrophy. Conversely to expected, heterotrophy was higher in unbleached polyps (+54% mesozooplankton prey and +11% large prey). The increase of heterotrophic intake may not be always used as a strategy to compensate autotrophic depletion in bleached polyps. Such a resilience strategy might be more species-specific than expected.

Immunomodulatory Strategies for Cartilage Regeneration in Osteoarthritis.

Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability globally. Although many efforts have been made to treat this condition, current tissue engineering (TE) and regenerative medicine strategies fail to address the inflammatory tissue environment that leads to the rapid progression of the disease and prevents cartilage tissue formation. First, this review addresses in detail the current anti-inflammatory therapies for OA with a special emphasis on pharmacological approaches, gene therapy, and mesenchymal stromal cell (MSC) intra-articular administration, and discusses the reasons behind the limited clinical success of these approaches at enabling cartilage regeneration. Then, we analyze the state-of-the-art TE strategies and how they can be improved by incorporating immunomodulatory capabilities such as the optimization of biomaterial composition, porosity and geometry, and the loading of anti-inflammatory molecules within an engineered structure. Finally, the review discusses the future directions for the new generation of TE strategies for OA treatment, specifically focusing on the spatiotemporal modulation of anti-inflammatory agent presentation to allow for tailored patient-specific therapies. Impact statement Osteoarthritis (OA) is a prevalent and debilitating musculoskeletal disorder affecting millions worldwide. Despite significant advancements in regenerative medicine and tissue engineering (TE), mitigating inflammation while simultaneously promoting cartilage tissue regeneration in OA remains elusive. In this review article, we discuss current anti-inflammatory therapies and explore their potential synergy with cutting-edge cartilage TE strategies, with a special focus on novel spatiotemporal and patient-specific anti-inflammatory strategies.

Neutrophil Granulopoiesis Optimized Through Ex Vivo Expansion of Hematopoietic Progenitors in Engineered 3D Gelatin Methacrylate Hydrogels.

Neutrophils are the first line of defense of the innate immune system. In response to methicillin-resistant Staphylococcus aureus infection in the skin, hematopoietic stem, and progenitor cells (HSPCs) traffic to wounds and undergo extramedullary granulopoiesis, producing neutrophils necessary to resolve the infection. This prompted the engineering of a gelatin methacrylate (GelMA) hydrogel that encapsulates HSPCs within a matrix amenable to subcutaneous delivery. The authors study the influence of hydrogel mechanical properties to produce an artificial niche for granulocyte-monocyte progenitors (GMPs) to efficiently expand into functional neutrophils that can populate infected tissue. Lin-cKIT+ HSPCs, harvested from fluorescent neutrophil reporter mice, are encapsulated in GelMA hydrogels of varying polymer concentration and UV-crosslinked to produce HSPC-laden gels of specific stiffness and mesh sizes. Softer 5% GelMA gels yield the most viable progenitors and effective cell-matrix interactions. Compared to suspension culture, 5% GelMA results in a twofold expansion of mature neutrophils that retain antimicrobial functions including degranulation, phagocytosis, and ROS production. When implanted dermally in C57BL/6J mice, luciferase-expressing neutrophils expanded in GelMA hydrogels are visualized at the site of implantation for over 5 days. They demonstrate the potential of GelMA hydrogels for delivering HSPCs directly to the site of skin infection to promote local granulopoiesis.

Solvent-cast 3D printing with molecular weight polymer blends to decouple effects of scaffold architecture and mechanical properties on mesenchymal stromal cell fate.

The biochemical and physical properties of a scaffold can be tailored to elicit specific cellular responses. However, it is challenging to decouple their individual effects on cell-material interactions. Here, we solvent-cast 3D printed different ratios of high and low molecular weight (MW) poly(caprolactone) (PCL) to fabricate scaffolds with significantly different stiffnesses without affecting other properties. Ink viscosity was used to match processing conditions between inks and generate scaffolds with the same surface chemistry, crystallinity, filament diameter, and architecture. Increasing the ratio of low MW PCL resulted in a significant decrease in modulus. Scaffold modulus did not affect human mesenchymal stromal cell (hMSC) differentiation under osteogenic conditions. However, hMSC response was significantly affected by scaffold stiffness in chondrogenic media. Low stiffness promoted more stable chondrogenesis whereas high stiffness drove hMSC progression toward hypertrophy. These data illustrate how this versatile platform can be used to independently modify biochemical and physical cues in a single scaffold to synergistically enhance desired cellular response.