Sattwikesh Paul, Karsten Schrobback, Phong Anh Tran, Christoph Meinert, Jordan William Davern, Angus Weekes, Udhaya Nedunchezhiyan, Travis Jacob Klein
{"title":"GelMA-glycol chitosan hydrogels for cartilage regeneration: The role of uniaxial mechanical stimulation in enhancing mechanical, adhesive, and biochemical properties.","authors":"Sattwikesh Paul, Karsten Schrobback, Phong Anh Tran, Christoph Meinert, Jordan William Davern, Angus Weekes, Udhaya Nedunchezhiyan, Travis Jacob Klein","doi":"10.1063/5.0160472","DOIUrl":"https://doi.org/10.1063/5.0160472","url":null,"abstract":"<p><p>Untreated osteochondral defects are a leading cause of osteoarthritis, a condition that places a heavy burden on both patients and orthopedic surgeons. Although tissue engineering has shown promise for creating mechanically similar cartilage-like constructs, their integration with cartilage remains elusive. Therefore, a formulation of biodegradable, biocompatible biomaterial with sufficient mechanical and adhesive properties for cartilage repair is required. To accomplish this, we prepared biocompatible, photo-curable, mechanically robust, and highly adhesive GelMA-glycol chitosan (GelMA-GC) hydrogels. GelMA-GC hydrogels had a modulus of 283 kPa and provided a biocompatible environment (>70% viability of embedded chondrocytes) in long-term culture within a bovine cartilage ring. The adhesive strength of bovine chondrocyte-laden GelMA-GC hydrogel to bovine cartilage increased from 38 to 52 kPa over four weeks of culture. Moreover, intermittent uniaxial mechanical stimulation enhanced the adhesive strength to ∼60 kPa, indicating that the cartilage-hydrogel integration could remain secure and functional under dynamic loading conditions. Furthermore, gene expression data and immunofluorescence staining revealed the capacity of chondrocytes in GelMA-GC hydrogel to synthesize chondrogenic markers (COL2A1 and ACAN), suggesting the potential for tissue regeneration. The promising <i>in vitro</i> results of this work motivate further exploration of the potential of photo-curable GelMA-GC bioadhesive hydrogels for cartilage repair and regeneration.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036114"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10492648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2023-08-28eCollection Date: 2023-09-01DOI: 10.1063/5.0155862
Jae-Myeong Kwon, Sang-In Bae, Taehan Kim, Jeong Kun Kim, Ki-Hun Jeong
{"title":"Deep focus light-field camera for handheld 3D intraoral scanning using crosstalk-free solid immersion microlens arrays.","authors":"Jae-Myeong Kwon, Sang-In Bae, Taehan Kim, Jeong Kun Kim, Ki-Hun Jeong","doi":"10.1063/5.0155862","DOIUrl":"10.1063/5.0155862","url":null,"abstract":"<p><p>3D <i>in vivo</i> imaging techniques facilitate disease tracking and treatment, but bulky configurations and motion artifacts limit practical clinical applications. Compact light-field cameras with microlens arrays offer a feasible option for rapid volumetric imaging, yet their utilization in clinical practice necessitates an increased depth-of-field for handheld operation. Here, we report deep focus light-field camera (DF-LFC) with crosstalk-free solid immersion microlens arrays (siMLAs), allowing large depth-of-field and high-resolution imaging for handheld 3D intraoral scanning. The siMLAs consist of thin PDMS-coated microlens arrays and a metal-insulator-metal absorber to extend the focal length with low optical crosstalk and specular reflection. The experimental results show that the immersion of MLAs in PDMS increases the focal length by a factor of 2.7 and the transmittance by 5.6%-27%. Unlike conventional MLAs, the siMLAs exhibit exceptionally high <i>f</i>-numbers up to <i>f</i>/6, resulting in a large depth-of-field for light-field imaging. The siMLAs were fully integrated into an intraoral scanner to reconstruct a 3D dental phantom with a distance measurement error of 82 ± 41 <i>μ</i>m during handheld operation. The DF-LFC offers a new direction not only for digital dental impressions with high accuracy, simplified workflow, reduced waste, and digital compatibility but also for assorted clinical endoscopy and microscopy.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036110"},"PeriodicalIF":6.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10500912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2023-08-08eCollection Date: 2023-09-01DOI: 10.1063/5.0155207
Taylor Bertucci, Shravani Kakarla, Max A Winkelman, Keith Lane, Katherine Stevens, Steven Lotz, Alexander Grath, Daylon James, Sally Temple, Guohao Dai
{"title":"Direct differentiation of human pluripotent stem cells into vascular network along with supporting mural cells.","authors":"Taylor Bertucci, Shravani Kakarla, Max A Winkelman, Keith Lane, Katherine Stevens, Steven Lotz, Alexander Grath, Daylon James, Sally Temple, Guohao Dai","doi":"10.1063/5.0155207","DOIUrl":"10.1063/5.0155207","url":null,"abstract":"<p><p>During embryonic development, endothelial cells (ECs) undergo vasculogenesis to form a primitive plexus and assemble into networks comprised of mural cell-stabilized vessels with molecularly distinct artery and vein signatures. This organized vasculature is established prior to the initiation of blood flow and depends on a sequence of complex signaling events elucidated primarily in animal models, but less studied and understood in humans. Here, we have developed a simple vascular differentiation protocol for human pluripotent stem cells that generates ECs, pericytes, and smooth muscle cells simultaneously. When this protocol is applied in a 3D hydrogel, we demonstrate that it recapitulates the dynamic processes of early human vessel formation, including acquisition of distinct arterial and venous fates, resulting in a vasculogenesis angiogenesis model plexus (VAMP). The VAMP captures the major stages of vasculogenesis, angiogenesis, and vascular network formation and is a simple, rapid, scalable model system for studying early human vascular development <i>in vitro</i>.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036107"},"PeriodicalIF":6.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2023-08-04eCollection Date: 2023-09-01DOI: 10.1063/5.0146000
Yago Juste-Lanas, Silvia Hervas-Raluy, José Manuel García-Aznar, Alejandra González-Loyola
{"title":"Fluid flow to mimic organ function in 3D <i>in vitro</i> models.","authors":"Yago Juste-Lanas, Silvia Hervas-Raluy, José Manuel García-Aznar, Alejandra González-Loyola","doi":"10.1063/5.0146000","DOIUrl":"10.1063/5.0146000","url":null,"abstract":"<p><p>Many different strategies can be found in the literature to model organ physiology, tissue functionality, and disease <i>in vitro</i>; however, most of these models lack the physiological fluid dynamics present <i>in vivo</i>. Here, we highlight the importance of fluid flow for tissue homeostasis, specifically in vessels, other lumen structures, and interstitium, to point out the need of perfusion in current 3D <i>in vitro</i> models. Importantly, the advantages and limitations of the different current experimental fluid-flow setups are discussed. Finally, we shed light on current challenges and future focus of fluid flow models applied to the newest bioengineering state-of-the-art platforms, such as organoids and organ-on-a-chip, as the most sophisticated and physiological preclinical platforms.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"031501"},"PeriodicalIF":6.6,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2023-07-05eCollection Date: 2023-09-01DOI: 10.1063/5.0158324
James B Grotberg, Francesco Romanò
{"title":"Computational pulmonary edema: A microvascular model of alveolar capillary and interstitial flow.","authors":"James B Grotberg, Francesco Romanò","doi":"10.1063/5.0158324","DOIUrl":"10.1063/5.0158324","url":null,"abstract":"<p><p>We present a microvascular model of fluid transport in the alveolar septa related to pulmonary edema. It consists of a two-dimensional capillary sheet coursing by several alveoli. The alveolar epithelial membrane runs parallel to the capillary endothelial membrane with an interstitial layer in between, making one long septal tract. A coupled system of equations uses lubrication theory for the capillary blood, Darcy flow for the porous media of the interstitium, a passive alveolus, and the Starling equation at both membranes. Case examples include normal physiology, cardiogenic pulmonary edema, acute respiratory distress syndrome (ARDS), hypoalbuminemia, and effects of PEEP. COVID-19 has dramatically increased ARDS in the world population, raising the urgency for such a model to create an analytical framework. Under normal conditions fluid exits the alveolus, crosses the interstitium, and enters the capillary. For edema, this crossflow is reversed with fluid leaving the capillary and entering the alveolus. Because both the interstitial and capillary pressures decrease downstream, the reversal can occur within a single septal tract, with edema upstream and clearance downstream. Clinically useful solution forms are provided allowing calculation of interstitial fluid pressure, crossflows, and critical capillary pressures. Overall, the interstitial pressures are found to be significantly more positive than values used in the traditional physiological literature. That creates steep gradients near the upstream and downstream end outlets, driving significant flows toward the distant lymphatics. This new physiological flow provides an explanation to the puzzle, noted since 1896, of how pulmonary lymphatics can function so far from the alveoli: the interstitium is self-clearing.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036101"},"PeriodicalIF":6.0,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325818/pdf/ABPID9-000007-036101_1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2023-06-15eCollection Date: 2023-06-01DOI: 10.1063/5.0153214
Xinyuan Zhang, Milad Almasian, Sohail S Hassan, Rosemary Jotheesh, Vinay A Kadam, Austin R Polk, Alireza Saberigarakani, Aayan Rahat, Jie Yuan, Juhyun Lee, Kelli Carroll, Yichen Ding
{"title":"4D Light-sheet imaging and interactive analysis of cardiac contractility in zebrafish larvae.","authors":"Xinyuan Zhang, Milad Almasian, Sohail S Hassan, Rosemary Jotheesh, Vinay A Kadam, Austin R Polk, Alireza Saberigarakani, Aayan Rahat, Jie Yuan, Juhyun Lee, Kelli Carroll, Yichen Ding","doi":"10.1063/5.0153214","DOIUrl":"10.1063/5.0153214","url":null,"abstract":"<p><p>Despite ongoing efforts in cardiovascular research, the acquisition of high-resolution and high-speed images for the purpose of assessing cardiac contraction remains challenging. Light-sheet fluorescence microscopy (LSFM) offers superior spatiotemporal resolution and minimal photodamage, providing an indispensable opportunity for the <i>in vivo</i> study of cardiac micro-structure and contractile function in zebrafish larvae. To track the myocardial architecture and contractility, we have developed an imaging strategy ranging from LSFM system construction, retrospective synchronization, single cell tracking, to user-directed virtual reality (VR) analysis. Our system enables the four-dimensional (4D) investigation of individual cardiomyocytes across the entire atrium and ventricle during multiple cardiac cycles in a zebrafish larva at the cellular resolution. To enhance the throughput of our model reconstruction and assessment, we have developed a parallel computing-assisted algorithm for 4D synchronization, resulting in a nearly tenfold enhancement of reconstruction efficiency. The machine learning-based nuclei segmentation and VR-based interaction further allow us to quantify cellular dynamics in the myocardium from end-systole to end-diastole. Collectively, our strategy facilitates noninvasive cardiac imaging and user-directed data interpretation with improved efficiency and accuracy, holding great promise to characterize functional changes and regional mechanics at the single cell level during cardiac development and regeneration.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 2","pages":"026112"},"PeriodicalIF":6.6,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10070956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2023-06-09eCollection Date: 2023-06-01DOI: 10.1063/5.0151408
Annie Trinh, Yi Huang, Hanjuan Shao, Aparna Ram, Julien Morival, Jonathan Wang, Eun Ji Chung, Timothy L Downing
{"title":"Targeting the ADPKD methylome using nanoparticle-mediated combination therapy.","authors":"Annie Trinh, Yi Huang, Hanjuan Shao, Aparna Ram, Julien Morival, Jonathan Wang, Eun Ji Chung, Timothy L Downing","doi":"10.1063/5.0151408","DOIUrl":"10.1063/5.0151408","url":null,"abstract":"<p><p>DNA methylation aberrancies are found in autosomal dominant polycystic kidney disease (ADPKD), which suggests the methylome to be a promising therapeutic target. However, the impact of combining DNA methylation inhibitors (DNMTi) and ADPKD drugs in treating ADPKD and on disease-associated methylation patterns has not been fully explored. To test this, ADPKD drugs, metformin and tolvaptan (MT), were delivered in combination with DNMTi 5-aza-2'-deoxycytidine (Aza) to 2D or 3D cystic <i>Pkd1</i> heterozygous renal epithelial cells (PKD1-Het cells) as free drugs or within nanoparticles to enable direct delivery for future <i>in vivo</i> applications. We found Aza synergizes with MT to reduce cell viability and cystic growth. Reduced representation bisulfite sequencing (RRBS) was performed across four groups: PBS, Free-Aza (Aza), Free-Aza+MT (F-MTAza), and Nanoparticle-Aza+MT (NP-MTAza). Global methylation patterns showed that while Aza alone induces a unimodal intermediate methylation landscape, Aza+MT recovers the bimodality reminiscent of somatic methylomes. Importantly, site-specific methylation changes associated with F-MTAza and NP-MTAza were largely conserved including hypomethylation at ADPKD-associated genes. Notably, we report hypomethylation of cancer-associated genes implicated in ADPKD pathogenesis as well as new target genes that may provide additional therapeutic effects. Overall, this study motivates future work to further elucidate the regulatory mechanisms of observed drug synergy and apply these combination therapies <i>in vivo</i>.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 2","pages":"026111"},"PeriodicalIF":6.6,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pranjali Beri, Christopher Plunkett, Joshua Barbara, Chien-Cheng Shih, S Whitney Barnes, Olivia Ross, Paula Choconta, Ton Trinh, Datzael Gomez, Bella Litvin, John Walker, Minhua Qiu, Scott Hammack, Erin Quan Toyama
{"title":"A high-throughput 3D cantilever array to model airway smooth muscle hypercontractility in asthma.","authors":"Pranjali Beri, Christopher Plunkett, Joshua Barbara, Chien-Cheng Shih, S Whitney Barnes, Olivia Ross, Paula Choconta, Ton Trinh, Datzael Gomez, Bella Litvin, John Walker, Minhua Qiu, Scott Hammack, Erin Quan Toyama","doi":"10.1063/5.0132516","DOIUrl":"https://doi.org/10.1063/5.0132516","url":null,"abstract":"<p><p>Asthma is often characterized by tissue-level mechanical phenotypes that include remodeling of the airway and an increase in airway tightening, driven by the underlying smooth muscle. Existing therapies only provide symptom relief and do not improve the baseline narrowing of the airway or halt progression of the disease. To investigate such targeted therapeutics, there is a need for models that can recapitulate the 3D environment present in this tissue, provide phenotypic readouts of contractility, and be easily integrated into existing assay plate designs and laboratory automation used in drug discovery campaigns. To address this, we have developed DEFLCT, a high-throughput plate insert that can be paired with standard labware to easily generate high quantities of microscale tissues <i>in vitro</i> for screening applications. Using this platform, we exposed primary human airway smooth muscle cell-derived microtissues to a panel of six inflammatory cytokines present in the asthmatic niche, identifying TGF-β1 and IL-13 as inducers of a hypercontractile phenotype. RNAseq analysis further demonstrated enrichment of contractile and remodeling-relevant pathways in TGF-β1 and IL-13 treated tissues as well as pathways generally associated with asthma. Screening of 78 kinase inhibitors on TGF-β1 treated tissues suggests that inhibition of protein kinase C and mTOR/Akt signaling can prevent this hypercontractile phenotype from emerging, while direct inhibition of myosin light chain kinase does not. Taken together, these data establish a disease-relevant 3D tissue model for the asthmatic airway, which combines niche specific inflammatory cues and complex mechanical readouts that can be utilized in drug discovery efforts.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 2","pages":"026104"},"PeriodicalIF":6.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10662735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V Vurro, K Shani, H A M Ardoña, J F Zimmerman, V Sesti, K Y Lee, Q Jin, C Bertarelli, K K Parker, G Lanzani
{"title":"Light-triggered cardiac microphysiological model.","authors":"V Vurro, K Shani, H A M Ardoña, J F Zimmerman, V Sesti, K Y Lee, Q Jin, C Bertarelli, K K Parker, G Lanzani","doi":"10.1063/5.0143409","DOIUrl":"https://doi.org/10.1063/5.0143409","url":null,"abstract":"<p><p>Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an <i>in vitro</i> cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 2","pages":"026108"},"PeriodicalIF":6.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10208677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul J Besseling, Merle M Krebber, Joost O Fledderus, Martin Teraa, Krista den Ouden, Melanie van de Kaa, Petra M de Bree, Aurelie Serrero, Carlijn V C Bouten, Patricia Y W Dankers, Martijn A J Cox, Marianne C Verhaar
{"title":"The effect of chronic kidney disease on tissue formation of <i>in situ</i> tissue-engineered vascular grafts.","authors":"Paul J Besseling, Merle M Krebber, Joost O Fledderus, Martin Teraa, Krista den Ouden, Melanie van de Kaa, Petra M de Bree, Aurelie Serrero, Carlijn V C Bouten, Patricia Y W Dankers, Martijn A J Cox, Marianne C Verhaar","doi":"10.1063/5.0138808","DOIUrl":"https://doi.org/10.1063/5.0138808","url":null,"abstract":"<p><p>Vascular <i>in situ</i> tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on <i>in vivo</i> scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful <i>in vivo</i> application of a slow-degrading small-diameter vascular graft that supports adequate <i>in situ</i> vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red<sup>+</sup>, Sham 16.5% vs CKD 25.0%-p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%-p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 2","pages":"026107"},"PeriodicalIF":6.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10208679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}