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Article: Dantrolene inhibits lysophosphatidylcholine-induced valve interstitial cell calcific nodule formation

Sylvester, Christopher B / Amirkhosravi, Farshad / Bortoletto, Angelina S / West, William J / Connell, Jennifer P / Grande-Allen, K Jane

Frontiers in cardiovascular medicine

2023 Volume 10, Page(s) 1112965

Abstract: Calcific aortic valve disease (CAVD), a fibrocalcific thickening of the aortic valve leaflets causing obstruction of the left ventricular outflow tract, affects nearly 10 million people worldwide. For those who reach end-stage CAVD, the only treatment is ...

Abstract	Calcific aortic valve disease (CAVD), a fibrocalcific thickening of the aortic valve leaflets causing obstruction of the left ventricular outflow tract, affects nearly 10 million people worldwide. For those who reach end-stage CAVD, the only treatment is highly invasive valve replacement. The development of pharmaceutical treatments that can slow or reverse the progression in those affected by CAVD would greatly advance the treatment of this disease. The principal cell type responsible for the fibrocalcific thickening of the valve leaflets in CAVD is valvular interstitial cells (VICs). The cellular processes mediating this calcification are complex, but calcium second messenger signaling, regulated in part by the ryanodine receptor (RyR), has been shown to play a role in a number of other fibrocalcific diseases. We sought to determine if the blockade of calcium signaling in VICs could ameliorate calcification in an
Language	English
Publishing date	2023-03-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1112965
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bioinspired electrospun dECM scaffolds guide cell growth and control the formation of myotubes.

Smoak, Mollie M / Hogan, Katie J / Grande-Allen, K Jane / Mikos, Antonios G

Science advances

2021 Volume 7, Issue 20

Abstract: While skeletal muscle has a high capacity for endogenous repair in acute injuries, volumetric muscle loss can leave long-lasting or permanent structural and functional deficits to the injured muscle and surrounding tissues. With clinical treatments ... ...

Abstract	While skeletal muscle has a high capacity for endogenous repair in acute injuries, volumetric muscle loss can leave long-lasting or permanent structural and functional deficits to the injured muscle and surrounding tissues. With clinical treatments failing to repair lost tissue, there is a great need for a tissue-engineered therapy to promote skeletal muscle regeneration. In this study, we aim to assess the potential for electrospun decellularized skeletal muscle extracellular matrix (dECM) with tunable physicochemical properties to control mouse myoblast growth and myotube formation. The material properties as well as cell behavior - growth and differentiation - were assessed in response to modulation of crosslinking and scaffold architecture. The fabrication of a bioactive dECM-based system with tunable physicochemical properties that can control myotube formation has several applications in skeletal muscle engineering and may bring the field one step closer to developing a therapy to address these unmet clinical needs.
Language	English
Publishing date	2021-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abg4123
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Article ; Online: Human gelatin-based composite hydrogels for osteochondral tissue engineering and their adaptation into bioinks for extrusion, inkjet, and digital light processing bioprinting.

Bedell, Matthew L / Torres, Angelica L / Hogan, Katie J / Wang, Ziwen / Wang, Bonnie / Melchiorri, Anthony J / Grande-Allen, K Jane / Mikos, Antonios G

Biofabrication

2022 Volume 14, Issue 4

Abstract: The investigation of novel hydrogel systems allows for the study of relationships between biomaterials, cells, and other factors within osteochondral tissue engineering. Three-dimensional (3D) printing is a popular research method that can allow for ... ...

Abstract	The investigation of novel hydrogel systems allows for the study of relationships between biomaterials, cells, and other factors within osteochondral tissue engineering. Three-dimensional (3D) printing is a popular research method that can allow for further interrogation of these questions via the fabrication of 3D hydrogel environments that mimic tissue-specific, complex architectures. However, the adaptation of promising hydrogel biomaterial systems into 3D-printable bioinks remains a challenge. Here, we delineated an approach to that process. First, we characterized a novel methacryloylated gelatin composite hydrogel system and assessed how calcium phosphate and glycosaminoglycan additives upregulated bone- and cartilage-like matrix deposition and certain genetic markers of differentiation within human mesenchymal stem cells (hMSCs), such as RUNX2 and SOX9. Then, new assays were developed and utilized to study the effects of xanthan gum and nanofibrillated cellulose, which allowed for cohesive fiber deposition, reliable droplet formation, and non-fracturing digital light processing (DLP)-printed constructs within extrusion, inkjet, and DLP techniques, respectively. Finally, these bioinks were used to 3D print constructs containing viable encapsulated hMSCs over a 7 d period, where DLP printed constructs facilitated the highest observed increase in cell number over 7 d (∼2.4×). The results presented here describe the promotion of osteochondral phenotypes via these novel composite hydrogel formulations, establish their ability to bioprint viable, cell-encapsulating constructs using three different 3D printing methods on multiple bioprinters, and document how a library of modular bioink additives affected those physicochemical properties important to printability.
MeSH term(s)	Bioprinting/methods ; Gelatin/chemistry ; Humans ; Hydrogels/chemistry ; Printing, Three-Dimensional ; Tissue Engineering/methods ; Tissue Scaffolds/chemistry
Chemical Substances	Hydrogels ; Gelatin (9000-70-8)
Language	English
Publishing date	2022-08-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2500944-8
ISSN	1758-5090 ; 1758-5082
ISSN (online)	1758-5090
ISSN	1758-5082
DOI	10.1088/1758-5090/ac8768
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Article: Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Farsheed, Adam C / Zevallos-Delgado, Christian / Yu, Le Tracy / Saeidifard, Sajede / Swain, Joseph W R / Makhoul, Jonathan T / Thomas, Adam J / Cole, Carson C / Huitron, Eric Garcia / Grande-Allen, K Jane / Singh, Manmohan / Larin, Kirill V / Hartgerink, Jeffrey D

bioRxiv : the preprint server for biology

2024

Abstract: Fibrous proteins that comprise the extracellular matrix (ECM) guide cellular growth and tissue organization. A lack of synthetic strategies able to generate aligned, ECM-mimetic biomaterials has hampered bottom-up tissue engineering of anisotropic ... ...

Abstract	Fibrous proteins that comprise the extracellular matrix (ECM) guide cellular growth and tissue organization. A lack of synthetic strategies able to generate aligned, ECM-mimetic biomaterials has hampered bottom-up tissue engineering of anisotropic tissues and led to a limited understanding of cell-matrix interactions. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical structures. We establish how modest changes in phosphate buffer concentration during peptide self-assembly can be used to tune their alignment and packing. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an ECM-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to generate a gradient of anisotropic nanofibrous hydrogels, which are used to better understand directed cell growth.
Language	English
Publishing date	2024-02-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.02.578651
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Article ; Online: Erratum to "BME 2.0: Engineering the Future of Medicine".

Miller, Michael I / Brightman, Andrew O / Epstein, Frederick H / Grande-Allen, K Jane / Green, Jordan J / Haase, Eileen / Laurencin, Cato T / Logsdon, Elizabeth / Gabhann, Feilim Mac / Ogle, Brenda / Wang, Chun / Wodicka, George R / Winslow, Raimond L

BME frontiers

2023 Volume 4, Page(s) 28

Abstract: This corrects the article DOI: 10.34133/bmef.0001.]. ...

Abstract	[This corrects the article DOI: 10.34133/bmef.0001.].
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Published Erratum
ISSN	2765-8031
ISSN (online)	2765-8031
DOI	10.34133/bmef.0028
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Article: Development of photoreactive demineralized bone matrix 3D printing colloidal inks for bone tissue engineering.

Hogan, Katie J / Öztatlı, Hayriye / Perez, Marissa R / Si, Sophia / Umurhan, Reyhan / Jui, Elysa / Wang, Ziwen / Jiang, Emily Y / Han, Sa R / Diba, Mani / Jane Grande-Allen, K / Garipcan, Bora / Mikos, Antonios G

Regenerative biomaterials

2023 Volume 10, Page(s) rbad090

Abstract: ... crosslinking with a UV dosage of 3 J/cm ...

Abstract	Demineralized bone matrix (DBM) has been widely used clinically for dental, craniofacial and skeletal bone repair, as an osteoinductive and osteoconductive material. 3D printing (3DP) enables the creation of bone tissue engineering scaffolds with complex geometries and porosity. Photoreactive methacryloylated gelatin nanoparticles (GNP-MAs) 3DP inks have been developed, which display gel-like behavior for high print fidelity and are capable of post-printing photocrosslinking for control of scaffold swelling and degradation. Here, novel DBM nanoparticles (DBM-NPs, ∼400 nm) were fabricated and characterized prior to incorporation in 3DP inks. The objectives of this study were to determine how these DBM-NPs would influence the printability of composite colloidal 3DP inks, assess the impact of ultraviolet (UV) crosslinking on 3DP scaffold swelling and degradation and evaluate the osteogenic potential of DBM-NP-containing composite colloidal scaffolds. The addition of methacryloylated DBM-NPs (DBM-NP-MAs) to composite colloidal inks (100:0, 95:5 and 75:25 GNP-MA:DBM-NP-MA) did not significantly impact the rheological properties associated with printability, such as viscosity and shear recovery or photocrosslinking. UV crosslinking with a UV dosage of 3 J/cm
Language	English
Publishing date	2023-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2799042-4
ISSN	2056-3426 ; 2056-3418
ISSN (online)	2056-3426
ISSN	2056-3418
DOI	10.1093/rb/rbad090
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Article ; Online: BME 2.0: Engineering the Future of Medicine.

Miller, Michael I / Brightman, Andrew O / Epstein, Frederick H / Grande-Allen, K Jane / Green, Jordan J / Haase, Eileen / Laurencin, Cato T / Logsdon, Elizabeth / Mac Gabhann, Feilim / Ogle, Brenda / Wang, Chun / Wodicka, George R / Winslow, Rai

BME frontiers

2023 Volume 4, Page(s) 1

Abstract: If the 20th century was the age of mapping and controlling the external world, the 21st century is the biomedical age of mapping and controlling the biological internal world. The biomedical age is bringing new technological breakthroughs for sensing and ...

Abstract	If the 20th century was the age of mapping and controlling the external world, the 21st century is the biomedical age of mapping and controlling the biological internal world. The biomedical age is bringing new technological breakthroughs for sensing and controlling human biomolecules, cells, tissues, and organs, which underpin new frontiers in the biomedical discovery, data, biomanufacturing, and translational sciences. This article reviews what we believe will be the next wave of biomedical engineering (BME) education in support of the biomedical age, what we have termed BME 2.0. BME 2.0 was announced on October 12 2017 at BMES 49 (https://www.bme.jhu.edu/news-events/news/miller-opens-2017-bmes-annual-meeting-with-vision-for-new-bme-era/). We present several principles upon which we believe the BME 2.0 curriculum should be constructed, and from these principles, we describe what view as the foundations that form the next generations of curricula in support of the BME enterprise. The core principles of BME 2.0 education are (a) educate students bilingually, from day 1, in the languages of modern molecular biology and the analytical modeling of complex biological systems; (b) prepare every student to be a biomedical data scientist; (c) build a unique BME community for discovery and innovation via a vertically integrated and convergent learning environment spanning the university and hospital systems; (d) champion an educational culture of inclusive excellence; and (e) codify in the curriculum ongoing discoveries at the frontiers of the discipline, thus ensuring BME 2.0 as a launchpad for training the future leaders of the biotechnology marketplaces. We envision that the BME 2.0 education is the path for providing every student with the training to lead in this new era of engineering the future of medicine in the 21st century.
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2765-8031
ISSN (online)	2765-8031
DOI	10.34133/bmef.0001
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Article ; Online: Assessment of spinal cord injury using ultrasound elastography in a rabbit model in vivo.

Tang, Songyuan / Weiner, Bradley / Taraballi, Francesca / Haase, Candice / Stetco, Eliana / Mehta, Shail Maharshi / Shajudeen, Peer / Hogan, Matthew / De Rosa, Enrica / Horner, Philip J / Grande-Allen, K Jane / Shi, Zhaoyue / Karmonik, Christof / Tasciotti, Ennio / Righetti, Raffaella

Scientific reports

2023 Volume 13, Issue 1, Page(s) 15323

Abstract: The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In ... ...

Abstract	The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young's modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.
MeSH term(s)	Animals ; Rabbits ; Elasticity Imaging Techniques ; Diffusion Tensor Imaging ; Spinal Cord Injuries/diagnostic imaging ; Lagomorpha
Language	English
Publishing date	2023-09-15
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-41172-8
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Article ; Online: The effect of multi-material architecture on the ex vivo osteochondral integration of bioprinted constructs.

Bedell, Matthew L / Wang, Ziwen / Hogan, Katie J / Torres, Angelica L / Pearce, Hannah A / Chim, Letitia K / Grande-Allen, K Jane / Mikos, Antonios G

Acta biomaterialia

2022 Volume 155, Page(s) 99–112

Abstract: Extrusion bioprinted constructs for osteochondral tissue engineering were fabricated to study the effect of multi-material architecture on encapsulated human mesenchymal stem cells' tissue-specific matrix deposition and integration into an ex vivo ... ...

Abstract	Extrusion bioprinted constructs for osteochondral tissue engineering were fabricated to study the effect of multi-material architecture on encapsulated human mesenchymal stem cells' tissue-specific matrix deposition and integration into an ex vivo porcine osteochondral explant model. Two extrusion fiber architecture groups with differing transition regions and degrees of bone- and cartilage-like bioink mixing were employed. The gradient fiber (G-Fib) architecture group showed an increase in chondral integration over time, 18.5 ± 0.7 kPa on Day 21 compared to 9.6 ± 1.6 kPa on Day 1 for the required peak push-out force, and the segmented fiber (S-Fib) architecture group did not, which corresponded to the increase in sulfated glycosaminoglycan deposition noted only in the G-Fib group and the staining for cellularity and tissue-specific matrix deposition at the fiber-defect boundary. Conversely, the S-Fib architecture was associated with significant mineralization over time, but the G-Fib architecture was not. Notably, both fiber groups also had similar chondral integration as a re-inserted osteochondral tissue control. While architecture did dictate differences in the cells' responses to their environment, architecture was not shown to distinguish a statistically significant difference in tissue integration via fiber push-out testing within a given time point or explant region. Use of this three-week osteochondral model demonstrates that these bioink formulations support the fabrication of cell-laden constructs that integrate into explanted tissue as capably as natural tissue and encapsulate osteochondral matrix-producing cells, and it also highlights the important role that spatial architecture plays in the engineering of multi-phasic tissue environments. STATEMENT OF SIGNIFICANCE: Here, an ex vivo model was used to interrogate fundamental questions about the effect of multi-material scaffold architectural choices on osteochondral tissue integration. Cell-encapsulating constructs resembling stratified osteochondral tissue were 3D printed with architecture consisting of either gradient transitions or segmented transitions between the bone-like and cartilage-like bioink regions. The printed constructs were assessed alongside re-inserted natural tissue plugs via mechanical tissue integration push-out testing, biochemical assays, and histology. Differences in osteochondral matrix deposition were observed based on architecture, and both printed groups demonstrated cartilage integration similar to the native tissue plug group. As 3D printing becomes commonplace within biomaterials and tissue engineering, this work illustrates critical 3D co-culture interactions and demonstrates the importance of considering architecture when interpreting the results of studies utilizing spatially complex, multi-material scaffolds.
MeSH term(s)	Swine ; Humans ; Animals ; Tissue Scaffolds ; Mesenchymal Stem Cells ; Tissue Engineering/methods ; Biocompatible Materials/pharmacology ; Cartilage ; Printing, Three-Dimensional ; Bioprinting/methods
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2022-11-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2022.11.014
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Article ; Online: The Pursuit of Engineering the Ideal Heart Valve Replacement or Repair: A Special Issue of the Annals of Biomedical Engineering.

Dasi, Lakshmi Prasad / Grande-Allen, Jane / Kunzelman, Karyn / Kuhl, Ellen

Annals of biomedical engineering

2017 Volume 45, Issue 2, Page(s) 307–309

MeSH term(s)	Biomedical Engineering ; Bioprosthesis ; Heart Valve Diseases/surgery ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Tissue Engineering
Language	English
Publishing date	2017-01-24
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	185984-5
ISSN	1573-9686 ; 0191-5649 ; 0090-6964
ISSN (online)	1573-9686
ISSN	0191-5649 ; 0090-6964
DOI	10.1007/s10439-017-1801-0
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