PMID- 35446569
OWN - NLM
STAT- Publisher
LR  - 20220421
IS  - 1520-5827 (Electronic)
IS  - 0743-7463 (Linking)
DP  - 2022 Apr 21
TI  - Nanoparticle Properties Influence Transendothelial Migration of Monocytes.
LID - 10.1021/acs.langmuir.2c00200 [doi]
AB  - Nanoparticle-based delivery of therapeutics to the brain has had limited clinical 
      impact due to challenges crossing the blood-brain barrier (BBB). Certain cells, 
      such as monocytes, possess the ability to migrate across the BBB, making them 
      attractive candidates for cell-based brain delivery strategies. In this work, we 
      explore nanoparticle design parameters that impact both monocyte association and 
      monocyte-mediated BBB transport. We use electrohydrodynamic jetting to prepare 
      nanoparticles of varying sizes, compositions, and elasticity to address their 
      impact on uptake by THP-1 monocytes and permeation across the BBB. An in vitro 
      human BBB model is developed using human cerebral microvascular endothelial cells 
      (hCMEC/D3) for the assessment of migration. We compare monocyte uptake of both 
      polymeric and synthetic protein nanoparticles (SPNPs) of various sizes, as well 
      as their effect on cell migration. SPNPs (human serum albumin/HSA or human 
      transferrin/TF) are shown to promote increased monocyte-mediated transport across 
      the BBB over polymeric nanoparticles. TF SPNPs (200 nm) associate readily, with 
      an average uptake of 138 particles/cell. Nanoparticle loading is shown to 
      influence the migration of THP-1 monocytes. The migration of monocytes loaded 
      with 200 nm TF and 200 nm HSA SPNPs was 2.3-fold and 2.1-fold higher than that of 
      an untreated control. RNA-seq analysis after TF SPNP treatment suggests that the 
      upregulation of several migration genes may be implicated in increased monocyte 
      migration (ex. integrin subunits α M and α L). Integrin β 2 chain combines with 
      either integrin subunit α M chain or integrin subunit α L chain to form 
      macrophage antigen 1 and lymphocyte function-associated antigen 1 integrins. Both 
      products play a pivotal role in the transendothelial migration cascade. Our 
      findings highlight the potential of SPNPs as drug and/or gene delivery platforms 
      for monocyte-mediated BBB transport, especially where conventional polymer 
      nanoparticles are ineffective or otherwise not desirable.
FAU - Habibi, Nahal
AU  - Habibi N
AD  - Biointerfaces Institute and Department of Chemical Engineering, University of 
      Michigan, Ann Arbor, Michigan 48109, United States.
FAU - Brown, Tyler D
AU  - Brown TD
AD  - Wyss Institute of Biologically Inspired Engineering, Harvard University, 3 
      Blackfan Circle, Boston, Massachusetts 02115, United States.
AD  - School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, 
      Cambridge, Massachusetts 02318, United States.
FAU - Adu-Berchie, Kwasi
AU  - Adu-Berchie K
AD  - Wyss Institute of Biologically Inspired Engineering, Harvard University, 3 
      Blackfan Circle, Boston, Massachusetts 02115, United States.
AD  - School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, 
      Cambridge, Massachusetts 02318, United States.
FAU - Christau, Stephanie
AU  - Christau S
AD  - Biointerfaces Institute and Department of Chemical Engineering, University of 
      Michigan, Ann Arbor, Michigan 48109, United States.
FAU - Raymond, Jeffery E
AU  - Raymond JE
AD  - Biointerfaces Institute and Department of Chemical Engineering, University of 
      Michigan, Ann Arbor, Michigan 48109, United States.
FAU - Mooney, David J
AU  - Mooney DJ
AUID- ORCID: 0000-0001-6299-1194
AD  - Wyss Institute of Biologically Inspired Engineering, Harvard University, 3 
      Blackfan Circle, Boston, Massachusetts 02115, United States.
AD  - School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, 
      Cambridge, Massachusetts 02318, United States.
FAU - Mitragotri, Samir
AU  - Mitragotri S
AUID- ORCID: 0000-0002-2459-8305
AD  - Wyss Institute of Biologically Inspired Engineering, Harvard University, 3 
      Blackfan Circle, Boston, Massachusetts 02115, United States.
AD  - School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, 
      Cambridge, Massachusetts 02318, United States.
FAU - Lahann, Joerg
AU  - Lahann J
AUID- ORCID: 0000-0002-3334-2053
AD  - Biointerfaces Institute and Department of Chemical Engineering, University of 
      Michigan, Ann Arbor, Michigan 48109, United States.
AD  - Department of Material Science & Engineering, Department of Macromolecular 
      Science & Engineering, and Department of Biomedical Engineering, University of 
      Michigan, Ann Arbor, Michigan 48109, United States.
LA  - eng
PT  - Journal Article
DEP - 20220421
PL  - United States
TA  - Langmuir
JT  - Langmuir : the ACS journal of surfaces and colloids
JID - 9882736
SB  - IM
EDAT- 2022/04/22 06:00
MHDA- 2022/04/22 06:00
CRDT- 2022/04/21 17:10
PHST- 2022/04/21 17:10 [entrez]
PHST- 2022/04/22 06:00 [pubmed]
PHST- 2022/04/22 06:00 [medline]
AID - 10.1021/acs.langmuir.2c00200 [doi]
PST - aheadofprint
SO  - Langmuir. 2022 Apr 21. doi: 10.1021/acs.langmuir.2c00200.

PMID- 35442107
OWN - NLM
STAT- Publisher
LR  - 20220420
IS  - 1937-3392 (Electronic)
IS  - 1937-3384 (Linking)
DP  - 2022 Apr 20
TI  - Viscoelastic Biomaterials for Tissue Regeneration.
LID - 10.1089/ten.TEC.2022.0040 [doi]
AB  - The extracellular matrix (ECM) mechanical properties regulate key cellular 
      processes in tissue development and regeneration. The majority of scientific 
      investigation has focused on ECM elasticity as the primary mechanical regulator 
      of cell and tissue behavior. However, all living tissues are viscoelastic, 
      exhibiting both solid- and liquid-like mechanical behavior. Despite increasing 
      evidence regarding the role of ECM viscoelasticity in directing cellular 
      behavior, this aspect is still largely overlooked in the design of biomaterials 
      for tissue regeneration. Recently, with the emergence of various bottom-up 
      material design strategies, new approaches can deliver unprecedented control over 
      biomaterial properties at multiple length scales, thus enabling the design of 
      viscoelastic biomaterials that mimic various aspect of the native tissue ECM 
      microenvironment. This review describes key considerations for the design of 
      viscoelastic biomaterials for tissue regeneration. We provide an overview of the 
      role of matrix viscoelasticity in directing cell behavior towards regenerative 
      outcomes, highlight recent strategies utilizing viscoelastic hydrogels for 
      regenerative therapies, and outline remaining challenges, potential solutions, 
      and emerging applications for viscoelastic biomaterials in tissue engineering and 
      regenerative medicine.
FAU - Wu, David Tiansui
AU  - Wu DT
AD  - Harvard University John A Paulson School of Engineering and Applied Sciences, 
      124077, Cambridge, Massachusetts, United States.
AD  - Harvard University Wyss Institute for Biologically Inspired Engineering, 465574, 
      Boston, Massachusetts, United States.
AD  - Harvard School of Dental Medicine, 124048, Oral Medicine, Infection, and 
      Immunity, Boston, Massachusetts, United States; davidt_wu@hsdm.harvard.edu.
FAU - Jeffreys, Nicholas
AU  - Jeffreys N
AD  - Harvard University John A Paulson School of Engineering and Applied Sciences, 
      124077, Cambridge, Massachusetts, United States.
AD  - Harvard University Wyss Institute for Biologically Inspired Engineering, 465574, 
      Boston, Massachusetts, United States; njeffreys@g.harvard.edu.
FAU - Diba, Mani
AU  - Diba M
AD  - Harvard University John A Paulson School of Engineering and Applied Sciences, 
      124077, Cambridge, Massachusetts, United States; diba@seas.harvard.edu.
FAU - Mooney, David J
AU  - Mooney DJ
AD  - Harvard University John A Paulson School of Engineering and Applied Sciences, 
      124077, Cambridge, Massachusetts, United States.
AD  - Harvard University Wyss Institute for Biologically Inspired Engineering, 465574, 
      Boston, Massachusetts, United States; mooneyd@seas.harvard.edu.
LA  - eng
PT  - Journal Article
DEP - 20220420
PL  - United States
TA  - Tissue Eng Part C Methods
JT  - Tissue engineering. Part C, Methods
JID - 101466663
SB  - IM
EDAT- 2022/04/21 06:00
MHDA- 2022/04/21 06:00
CRDT- 2022/04/20 12:13
PHST- 2022/04/20 12:13 [entrez]
PHST- 2022/04/21 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
AID - 10.1089/ten.TEC.2022.0040 [doi]
PST - aheadofprint
SO  - Tissue Eng Part C Methods. 2022 Apr 20. doi: 10.1089/ten.TEC.2022.0040.

PMID- 35437554
OWN - NLM
STAT- Publisher
LR  - 20220419
IS  - 1473-0189 (Electronic)
IS  - 1473-0189 (Linking)
DP  - 2022 Apr 19
TI  - Actuated 3D microgels for single cell mechanobiology.
LID - 10.1039/d2lc00203e [doi]
AB  - We present a new cell culture technology for large-scale mechanobiology studies 
      capable of generating and applying optically controlled uniform compression on 
      single cells in 3D. Mesenchymal stem cells (MSCs) are individually encapsulated 
      inside an optically triggered nanoactuator-alginate hybrid biomaterial using 
      microfluidics, and the encapsulating network isotropically compresses the cell 
      upon activation by light. The favorable biomolecular properties of alginate allow 
      cell culture in vitro up to a week. The mechanically active microgels are capable 
      of generating up to 15% compressive strain and forces reaching 400 nN. As a proof 
      of concept, we demonstrate the use of the mechanically active cell culture system 
      in mechanobiology by subjecting singly encapsulated MSCs to optically generated 
      isotropic compression and monitoring changes in intracellular calcium intensity.
FAU - Özkale, Berna
AU  - Özkale B
AUID- ORCID: 0000-0002-3016-9363
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, MA, 02138, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA.
FAU - Lou, Junzhe
AU  - Lou J
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, MA, 02138, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA.
FAU - Özelçi, Ece
AU  - Özelçi E
AUID- ORCID: 0000-0001-7722-0130
AD  - Institute of Mechanical Engineering and Institute of Bioengineering, Ecole 
      Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland. 
      selman.sakar@epfl.ch.
FAU - Elosegui-Artola, Alberto
AU  - Elosegui-Artola A
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, MA, 02138, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA.
FAU - Tringides, Christina M
AU  - Tringides CM
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, MA, 02138, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA.
FAU - Mao, Angelo S
AU  - Mao AS
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, MA, 02138, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA.
FAU - Sakar, Mahmut Selman
AU  - Sakar MS
AUID- ORCID: 0000-0002-7226-3382
AD  - Institute of Mechanical Engineering and Institute of Bioengineering, Ecole 
      Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland. 
      selman.sakar@epfl.ch.
FAU - Mooney, David J
AU  - Mooney DJ
AUID- ORCID: 0000-0001-6299-1194
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, MA, 02138, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA.
LA  - eng
PT  - Journal Article
DEP - 20220419
PL  - England
TA  - Lab Chip
JT  - Lab on a chip
JID - 101128948
SB  - IM
EDAT- 2022/04/20 06:00
MHDA- 2022/04/20 06:00
CRDT- 2022/04/19 06:00
PHST- 2022/04/19 06:00 [entrez]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
AID - 10.1039/d2lc00203e [doi]
PST - aheadofprint
SO  - Lab Chip. 2022 Apr 19. doi: 10.1039/d2lc00203e.

PMID- 35313273
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20220405
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 283
DP  - 2022 Apr
TI  - Development of a liposomal near-infrared fluorescence lactate assay for human 
      blood.
PG  - 121475
LID - S0142-9612(22)00114-4 [pii]
LID - 10.1016/j.biomaterials.2022.121475 [doi]
AB  - In emergency medicine, blood lactate is a commonly used biomarker of hypoxia 
      (e.g., sepsis, trauma, cardiac arrest) but the median time to obtain the results 
      from a clinical lactate test is 3 h. We recently developed a near-infrared 
      fluorescent blood lactate assay based on a two-step enzymatic cascade in a 
      vesicular reaction compartment. Previously, we reported a response of this assay 
      to lactate-spiked bovine blood after 10 min. To develop a point-of-care test, we 
      optimized this assay in commercial human blood, validated it in fresh capillary 
      blood of healthy volunteers in an institutional review board-approved study, and 
      improved the stability of the formulation. External pH and luminal enzyme 
      concentrations were identified as key parameters of sensor response and kinetics, 
      as they impact transmembrane lactate diffusion and turnover rate. The preparation 
      process was also simplified and the stability was improved to allow storage at 
      4 °C for at least 5 days. The final formulation exhibited a strong and linear 
      response to lactate-spiked human blood in a clinically relevant range, and 
      accurately quantified a lactate standard at a clinically used cut-off in fresh 
      capillary blood after 2 min. These findings motivate a clinical evaluation of 
      this rapid and easy-to-use lactate assay.
CI  - Copyright © 2022 Elsevier Ltd. All rights reserved.
FAU - Matoori, Simon
AU  - Matoori S
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute Biologically Inspired Engineering, 
      Harvard University, Boston, MA, 02115, USA; Faculté de Pharmacie, Université de 
      Montréal, Montreal, QC H3T 1J4, Canada.
FAU - Mooney, David J
AU  - Mooney DJ
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute Biologically Inspired Engineering, 
      Harvard University, Boston, MA, 02115, USA. Electronic address: 
      mooneyd@seas.harvard.edu.
LA  - eng
PT  - Journal Article
DEP - 20220318
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Liposomes)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Fluorescence
MH  - Humans
MH  - Kinetics
MH  - *Lactic Acid
MH  - Liposomes
MH  - *Sepsis
OTO - NOTNLM
OT  - Human blood
OT  - Hydrogen peroxide
OT  - Lactate
OT  - Lactate assay
OT  - Liposome
EDAT- 2022/03/22 06:00
MHDA- 2022/04/06 06:00
CRDT- 2022/03/21 20:12
PHST- 2021/08/01 00:00 [received]
PHST- 2022/02/17 00:00 [revised]
PHST- 2022/03/16 00:00 [accepted]
PHST- 2022/03/22 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2022/03/21 20:12 [entrez]
AID - S0142-9612(22)00114-4 [pii]
AID - 10.1016/j.biomaterials.2022.121475 [doi]
PST - ppublish
SO  - Biomaterials. 2022 Apr;283:121475. doi: 10.1016/j.biomaterials.2022.121475. Epub 
      2022 Mar 18.

PMID- 35278685
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220426
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 143
DP  - 2022 Apr 15
TI  - Aging and matrix viscoelasticity affect multiscale tendon properties and tendon 
      derived cell behavior.
PG  - 63-71
LID - S1742-7061(22)00137-4 [pii]
LID - 10.1016/j.actbio.2022.03.006 [doi]
AB  - Aging is the largest risk factor for Achilles tendon associated disorders and 
      rupture. Although Achilles tendon macroscale elastic properties are suggested to 
      decline with aging, less is known about the effect of maturity and aging on 
      multiscale viscoelastic properties and their effect on tendon cell behavior. 
      Here, we show dose dependent changes in native multiscale tendon mechanical and 
      structural properties and uncover several nanoindentation properties predicted by 
      tensile mechanics and echogenicity. Alginate hydrogel systems designed to mimic 
      juvenile tendon microscale mechanics revealed that stiffness and viscoelasticity 
      affected Achilles tendon cell aspect ratio and proliferation during aging. This 
      knowledge provides further evidence for the negative impact of maturity and aging 
      on tendon and begins to elucidate how viscoelasticity can control tendon derived 
      cell morphology and expansion. STATEMENT OF SIGNIFICANCE: Aging is the largest 
      risk factor for Achilles tendon associated disorders and rupture. Although 
      Achilles tendon macroscale elastic properties are suggested to decline with 
      aging, less is known about the effect of maturity and aging on multiscale 
      viscoelastic properties and their effect on tendon cell behavior. Here, we show 
      dose dependent changes in native multiscale tendon mechanical and structural 
      properties and uncover several nanoindentation properties predicted by tensile 
      mechanics and echogenicity. Alginate hydrogel systems designed to mimic juvenile 
      tendon microscale mechanics revealed that stiffness and viscoelasticity affected 
      Achilles tendon cell spreading and proliferation during aging. This knowledge 
      provides further evidence for the negative impact of maturity and aging on tendon 
      and begins to elucidate how viscoelasticity can control tendon derived cell 
      morphology and expansion.
CI  - Copyright © 2022. Published by Elsevier Ltd.
FAU - Freedman, Benjamin R
AU  - Freedman BR
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      319 Pierce Hall, Cambridge, MA 02138, United States; Wyss Institute for 
      Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
FAU - Knecht, Raphael S
AU  - Knecht RS
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      319 Pierce Hall, Cambridge, MA 02138, United States; Wyss Institute for 
      Biologically Inspired Engineering, Harvard University, Boston, MA, United States; 
      Julius Wolff Institute and Center for Musculoskeletal Surgery, 
      Charité-Universitätsmedizin Berlin, Berlin, Germany.
FAU - Tinguely, Yann
AU  - Tinguely Y
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      319 Pierce Hall, Cambridge, MA 02138, United States; Wyss Institute for 
      Biologically Inspired Engineering, Harvard University, Boston, MA, United States; 
      École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
FAU - Eskibozkurt, G Ege
AU  - Eskibozkurt GE
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      319 Pierce Hall, Cambridge, MA 02138, United States; Wyss Institute for 
      Biologically Inspired Engineering, Harvard University, Boston, MA, United States; 
      Harvard Medical School, Boston, MA, United States.
FAU - Wang, Cathy S
AU  - Wang CS
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      319 Pierce Hall, Cambridge, MA 02138, United States; Massachusetts Institute of 
      Technology, Cambridge, MA, United States.
FAU - Mooney, David J
AU  - Mooney DJ
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      319 Pierce Hall, Cambridge, MA 02138, United States; Wyss Institute for 
      Biologically Inspired Engineering, Harvard University, Boston, MA, United States. 
      Electronic address: mooneyd@seas.harvard.edu.
LA  - eng
PT  - Journal Article
DEP - 20220309
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Alginates)
RN  - 0 (Hydrogels)
SB  - IM
MH  - *Achilles Tendon
MH  - Aging
MH  - Alginates/pharmacology
MH  - Humans
MH  - Hydrogels
MH  - Rupture
MH  - Viscosity
OTO - NOTNLM
OT  - Alginate
OT  - Collagen
OT  - Hydrogel
OT  - Tendon
OT  - Viscoelasticity
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/03/13 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/03/12 20:10
PHST- 2021/12/19 00:00 [received]
PHST- 2022/03/02 00:00 [revised]
PHST- 2022/03/03 00:00 [accepted]
PHST- 2022/03/13 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/03/12 20:10 [entrez]
AID - S1742-7061(22)00137-4 [pii]
AID - 10.1016/j.actbio.2022.03.006 [doi]
PST - ppublish
SO  - Acta Biomater. 2022 Apr 15;143:63-71. doi: 10.1016/j.actbio.2022.03.006. Epub 
      2022 Mar 9.

PMID- 35143595
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220228
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 18
IP  - 2
DP  - 2022 Feb
TI  - Antiplatelet therapy for Staphylococcus aureus bacteremia: Will it stick?
PG  - e1010240
LID - 10.1371/journal.ppat.1010240 [doi]
LID - e1010240
AB  - Staphylococcus aureus bacteremia (SAB) remains a clinically challenging infection 
      despite extensive investigation. Repurposing medications approved for other 
      indications is appealing as clinical safety profiles have already been 
      established. Ticagrelor, a reversible adenosine diphosphate receptor antagonist 
      that prevents platelet aggregation, is indicated for patients suffering from 
      acute coronary syndrome (ACS). However, some clinical data suggest that patients 
      treated with ticagrelor are less likely to have poor outcomes due to S. aureus 
      infection. There are several potential mechanisms by which ticagrelor may affect 
      S. aureus virulence. These include direct antibacterial activity, up-regulation 
      of the innate immune system through boosting platelet-mediated S. aureus killing, 
      and prevention of S. aureus adhesion to host tissues. In this Pearl, we review 
      the clinical data surrounding ticagrelor and infection as well as explore the 
      evidence surrounding these proposed mechanisms of action. While more evidence is 
      needed before antiplatelet medications formally become part of the arsenal 
      against S. aureus infection, these potential mechanisms represent exciting 
      pathways to target in the host/pathogen interface.
FAU - Tatara, Alexander M
AU  - Tatara AM
AUID- ORCID: 0000-0001-8579-4302
AD  - Division of Infectious Diseases, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      Massachusetts, United States of America.
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, Massachusetts, United States of America.
FAU - Gandhi, Ronak G
AU  - Gandhi RG
AD  - Department of Pharmacy, Massachusetts General Hospital, Boston, Massachusetts, 
      United States of America.
FAU - Mooney, David J
AU  - Mooney DJ
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      Massachusetts, United States of America.
AD  - Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard 
      University, Cambridge, Massachusetts, United States of America.
FAU - Nelson, Sandra B
AU  - Nelson SB
AUID- ORCID: 0000-0002-1949-7884
AD  - Division of Infectious Diseases, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
LA  - eng
GR  - T32 AI007061/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20220210
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - GLH0314RVC (Ticagrelor)
SB  - IM
MH  - Bacteremia/*drug therapy
MH  - Blood Platelets/*drug effects
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Immunity, Innate
MH  - Platelet Aggregation Inhibitors/therapeutic use
MH  - Staphylococcal Infections/*drug therapy/immunology/microbiology
MH  - Staphylococcus aureus/*drug effects/immunology
MH  - Ticagrelor/*therapeutic use
PMC - PMC8830658
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/02/11 06:00
MHDA- 2022/03/01 06:00
CRDT- 2022/02/10 17:15
PHST- 2022/02/10 17:15 [entrez]
PHST- 2022/02/11 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
AID - PPATHOGENS-D-21-02270 [pii]
AID - 10.1371/journal.ppat.1010240 [doi]
PST - epublish
SO  - PLoS Pathog. 2022 Feb 10;18(2):e1010240. doi: 10.1371/journal.ppat.1010240. 
      eCollection 2022 Feb.

PMID- 35133789
OWN - NLM
STAT- Publisher
LR  - 20220208
IS  - 2373-9878 (Electronic)
IS  - 2373-9878 (Linking)
DP  - 2022 Feb 8
TI  - Recent and Future Strategies of Mechanotherapy for Tissue Regenerative 
      Rehabilitation.
LID - 10.1021/acsbiomaterials.1c01477 [doi]
AB  - Mechanotherapy, the application of various mechanical forces on injured or 
      diseased tissue, is a viable option for tissue regenerative rehabilitation. 
      Recent advances in tissue engineering (i.e., engineered materials and 3D 
      printing) and soft-robotic technologies have enabled systematic and controlled 
      studies to demonstrate the therapeutic impacts of mechanical stimulation on 
      severely injured tissue. Along with innovation in actuation systems, improvements 
      in analysis methods uncovering cellular and molecular landscapes during tissue 
      regeneration under mechanical loading expand our understanding of how mechanical 
      cues are translated into specific biological responses (i.e., stem cell 
      self-renewal and differentiation, immune responses, etc.). Moving forward, the 
      development of diversified actuation systems that are mechanically tissue 
      friendly, easily scalable, and capable of delivering various modes of loading and 
      monitoring functional biomarkers will facilitate systematic and controlled 
      preclinical and clinical studies. Combining these future actuation systems with 
      single-cell resolution analysis of cellular and molecular markers will enable 
      detailed knowledge of underlying biological responses, and optimization of 
      mechanotherapy protocols for specific tissues/injuries. These advancements will 
      enable diverse mechanotherapy therapies in the future.
FAU - Seo, Bo Ri
AU  - Seo BR
AUID- ORCID: 0000-0002-0871-015X
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, Massachusetts 02138, United States.
AD  - Wyss Institute Biologically Inspired Engineering, Harvard University, Boston, 
      Massachusetts 02115, United States.
FAU - Mooney, David J
AU  - Mooney DJ
AUID- ORCID: 0000-0001-6299-1194
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, Massachusetts 02138, United States.
AD  - Wyss Institute Biologically Inspired Engineering, Harvard University, Boston, 
      Massachusetts 02115, United States.
LA  - eng
PT  - Journal Article
DEP - 20220208
PL  - United States
TA  - ACS Biomater Sci Eng
JT  - ACS biomaterials science & engineering
JID - 101654670
SB  - IM
OTO - NOTNLM
OT  - mechanotherapy
OT  - soft-robotic technologies
OT  - tissue engineering
OT  - tissue regenerative rehabilitation
EDAT- 2022/02/09 06:00
MHDA- 2022/02/09 06:00
CRDT- 2022/02/08 17:12
PHST- 2022/02/08 17:12 [entrez]
PHST- 2022/02/09 06:00 [pubmed]
PHST- 2022/02/09 06:00 [medline]
AID - 10.1021/acsbiomaterials.1c01477 [doi]
PST - aheadofprint
SO  - ACS Biomater Sci Eng. 2022 Feb 8. doi: 10.1021/acsbiomaterials.1c01477.

PMID- 34980903
OWN - NLM
STAT- Publisher
LR  - 20220419
IS  - 2157-846X (Electronic)
IS  - 2157-846X (Linking)
DP  - 2022 Jan 3
TI  - Enhanced tendon healing by a tough hydrogel with an adhesive side and high 
      drug-loading capacity.
LID - 10.1038/s41551-021-00810-0 [doi]
AB  - Hydrogels that provide mechanical support and sustainably release therapeutics 
      have been used to treat tendon injuries. However, most hydrogels are 
      insufficiently tough, release drugs in bursts, and require cell infiltration or 
      suturing to integrate with surrounding tissue. Here we report that a hydrogel 
      serving as a high-capacity drug depot and combining a dissipative tough matrix on 
      one side and a chitosan adhesive surface on the other side supports tendon 
      gliding and strong adhesion (larger than 1,000 J m(-2)) to tendon on opposite 
      surfaces of the hydrogel, as we show with porcine and human tendon preparations 
      during cyclic-friction loadings. The hydrogel is biocompatible, strongly adheres 
      to patellar, supraspinatus and Achilles tendons of live rats, boosted healing and 
      reduced scar formation in a rat model of Achilles-tendon rupture, and sustainably 
      released the corticosteroid triamcinolone acetonide in a rat model of patellar 
      tendon injury, reducing inflammation, modulating chemokine secretion, recruiting 
      tendon stem and progenitor cells, and promoting macrophage polarization to the M2 
      phenotype. Hydrogels with 'Janus' surfaces and sustained-drug-release 
      functionality could be designed for a range of biomedical applications.
CI  - © 2022. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Freedman, Benjamin R
AU  - Freedman BR
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, USA.
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      MA, USA.
FAU - Kuttler, Andreas
AU  - Kuttler A
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Beckmann, Nicolau
AU  - Beckmann N
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Nam, Sungmin
AU  - Nam S
AUID- ORCID: 0000-0003-1016-3738
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, USA.
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      MA, USA.
FAU - Kent, Daniel
AU  - Kent D
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      MA, USA.
FAU - Schuleit, Michael
AU  - Schuleit M
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Ramazani, Farshad
AU  - Ramazani F
AUID- ORCID: 0000-0002-8158-5658
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Accart, Nathalie
AU  - Accart N
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Rock, Anna
AU  - Rock A
AUID- ORCID: 0000-0002-6648-4496
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      MA, USA.
FAU - Li, Jianyu
AU  - Li J
AD  - Department of Mechanical Engineering, McGill University, Montreal, Quebec, 
      Canada.
FAU - Kurz, Markus
AU  - Kurz M
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Fisch, Andreas
AU  - Fisch A
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Ullrich, Thomas
AU  - Ullrich T
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland.
FAU - Hast, Michael W
AU  - Hast MW
AD  - Biedermann Lab for Orthopaedic Research, Department of Orthopaedic Surgery, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Tinguely, Yann
AU  - Tinguely Y
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      MA, USA.
FAU - Weber, Eckhard
AU  - Weber E
AUID- ORCID: 0000-0002-1762-005X
AD  - Novartis Institutes for Biomedical Research, Basel, Switzerland. 
      eckhard.weber@novartis.com.
FAU - Mooney, David J
AU  - Mooney DJ
AUID- ORCID: 0000-0001-6299-1194
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, USA. mooneyd@seas.harvard.edu.
AD  - Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 
      MA, USA. mooneyd@seas.harvard.edu.
LA  - eng
GR  - K99AG065495/U.S. Department of Health & Human Services | NIH | National Institute 
      on Aging (U.S. National Institute on Aging)/
PT  - Journal Article
DEP - 20220103
PL  - England
TA  - Nat Biomed Eng
JT  - Nature biomedical engineering
JID - 101696896
SB  - IM
EDAT- 2022/01/05 06:00
MHDA- 2022/01/05 06:00
CRDT- 2022/01/04 06:04
PHST- 2020/09/29 00:00 [received]
PHST- 2021/09/13 00:00 [accepted]
PHST- 2022/01/05 06:00 [pubmed]
PHST- 2022/01/05 06:00 [medline]
PHST- 2022/01/04 06:04 [entrez]
AID - 10.1038/s41551-021-00810-0 [pii]
AID - 10.1038/s41551-021-00810-0 [doi]
PST - aheadofprint
SO  - Nat Biomed Eng. 2022 Jan 3. doi: 10.1038/s41551-021-00810-0.

PMID- 34954588
OWN - NLM
STAT- MEDLINE
DCOM- 20220413
LR  - 20220413
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 281
DP  - 2022 Feb
TI  - Cryogel vaccines effectively induce immune responses independent of proximity to 
      the draining lymph nodes.
PG  - 121329
LID - S0142-9612(21)00685-2 [pii]
LID - 10.1016/j.biomaterials.2021.121329 [doi]
AB  - The delivery location of traditional vaccines can impact immune responses and 
      resulting efficacy. Cryogel-based cancer vaccines, which are typically injected 
      near the inguinal lymph nodes (iLNs), recruit and activate dendritic cells (DC) 
      in situ, induce DC homing to the iLNs, and have generated potent anti-tumor 
      immunity against several murine cancer models. However, whether cryogel 
      vaccination distance to a draining LN affects the kinetics of DC homing and 
      downstream antigen-specific immunity is unknown, given the heightened importance 
      of the scaffold vaccine site. We hypothesized that vaccination near the iLNs 
      would lead to more rapid DC trafficking to the iLNs, thereby inducing faster and 
      stronger immune responses. Here, mice were injected with cryogel vaccines against 
      ovalbumin either adjacent or distal to the iLNs, and the resultant DC trafficking 
      kinetics, T cell phenotypes, antigen-specific T cell and humoral responses, and 
      prophylactic efficacy in an ovalbumin-expressing tumor model were assessed. 
      Cryogel vaccines induced potent, long-lasting antigen-specific immune responses 
      independent of distance to the iLNs, with no significant differences in DC 
      trafficking kinetics, ovalbumin-specific T cell and antibody responses, or 
      prophylactic efficacy. Moreover, DC trafficking and activation state were not 
      impacted when cryogels were injected near a tumor. These results demonstrate a 
      flexibility in vaccination location for scaffold-based vaccines, independent of 
      draining LN distance.
CI  - Copyright © 2021 Elsevier Ltd. All rights reserved.
FAU - Najibi, Alexander J
AU  - Najibi AJ
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA.
FAU - Shih, Ting-Yu
AU  - Shih TY
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA.
FAU - Mooney, David J
AU  - Mooney DJ
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA. Electronic address: 
      mooneyd@seas.harvard.edu.
LA  - eng
GR  - R01 EB015498/EB/NIBIB NIH HHS/United States
GR  - R01 DK098055/DK/NIDDK NIH HHS/United States
GR  - R01 CA223255/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211222
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Antigens)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cryogels)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Antigens
MH  - *Cancer Vaccines
MH  - Cryogels
MH  - Dendritic Cells
MH  - Immunity
MH  - Lymph Nodes
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Neoplasms
MH  - Ovalbumin
OTO - NOTNLM
OT  - *Cancer vaccines
OT  - *Cryogels
OT  - *Draining lymph nodes
OT  - *Scaffold-based
OT  - *Vaccination location
EDAT- 2021/12/27 06:00
MHDA- 2022/04/14 06:00
CRDT- 2021/12/26 20:53
PHST- 2021/08/05 00:00 [received]
PHST- 2021/12/08 00:00 [revised]
PHST- 2021/12/18 00:00 [accepted]
PHST- 2021/12/27 06:00 [pubmed]
PHST- 2022/04/14 06:00 [medline]
PHST- 2021/12/26 20:53 [entrez]
AID - S0142-9612(21)00685-2 [pii]
AID - 10.1016/j.biomaterials.2021.121329 [doi]
PST - ppublish
SO  - Biomaterials. 2022 Feb;281:121329. doi: 10.1016/j.biomaterials.2021.121329. Epub 
      2021 Dec 22.

PMID- 34753036
OWN - NLM
STAT- MEDLINE
DCOM- 20211214
LR  - 20211214
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 279
DP  - 2021 Dec
TI  - Ultrasound-triggered release reveals optimal timing of CpG-ODN delivery from a 
      cryogel cancer vaccine.
PG  - 121240
LID - S0142-9612(21)00597-4 [pii]
LID - 10.1016/j.biomaterials.2021.121240 [doi]
AB  - Recently, several injectable scaffold-based cancer vaccines have been developed 
      that can recruit and activate host dendritic cells (DCs) and generate potent 
      antitumor responses. However, the optimal timing of adjuvant delivery, 
      particularly of the commonly used cytosine-phosphodiester-guanine-oligonucleotide 
      (CpG-ODN), for scaffold-based cancer vaccines remains unknown. We hypothesized 
      that optimally timed CpG-ODN delivery will lead to enhanced immune responses, and 
      designed a cryogel vaccine system where CpG-ODN release can be triggered 
      on-demand by ultrasound. CpG-ODN was first condensed with polyethylenimine and 
      then adsorbed to cryogels. Little adsorbed CpG-ODN was released in vitro. 
      Ultrasound stimulation triggered continuous CpG-ODN release, at an enhanced rate 
      even after ultrasound was turned off, with minimal burst release. In vivo, 
      ultrasound stimulation four days post-vaccination induced a significantly higher 
      antigen-specific cytotoxic T-lymphocyte (CTL) response compared to control mice. 
      Furthermore, ultrasound stimulation at this time point generated a significantly 
      higher IgG2a/c antibody titer than all the groups except ultrasound stimulation 
      eight days post-vaccination. This optimal timing of ultrasound-triggered release 
      coincided with peak DC accumulation in the cryogels. By enabling temporal control 
      of vaccine components through release on-demand, this system is a promising 
      platform to study the optimal timing of delivery of immunomodulatory agents for 
      cancer vaccination.
CI  - Copyright © 2021 Elsevier Ltd. All rights reserved.
FAU - Shih, Ting-Yu
AU  - Shih TY
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA.
FAU - Najibi, Alexander J
AU  - Najibi AJ
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA.
FAU - Bartlett, Alexandra L
AU  - Bartlett AL
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA.
FAU - Li, Aileen W
AU  - Li AW
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA.
FAU - Mooney, David J
AU  - Mooney DJ
AD  - John A. Paulson School of Engineering and Applied Sciences, Harvard University, 
      Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering 
      at Harvard University, Boston, MA, 02115, USA. Electronic address: 
      mooneyd@seas.harvard.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211103
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cryogels)
RN  - 0 (Immunomodulating Agents)
RN  - 0 (Oligodeoxyribonucleotides)
SB  - IM
MH  - Adjuvants, Immunologic
MH  - Animals
MH  - *Cancer Vaccines
MH  - Cryogels
MH  - Immunomodulating Agents
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Neoplasms
MH  - Oligodeoxyribonucleotides
MH  - T-Lymphocytes, Cytotoxic
OTO - NOTNLM
OT  - *Alginate
OT  - *Cancer vaccines
OT  - *Cryogels
OT  - *Ultrasound stimulation
EDAT- 2021/11/10 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/11/09 20:18
PHST- 2021/07/19 00:00 [received]
PHST- 2021/10/29 00:00 [revised]
PHST- 2021/11/02 00:00 [accepted]
PHST- 2021/11/10 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/11/09 20:18 [entrez]
AID - S0142-9612(21)00597-4 [pii]
AID - 10.1016/j.biomaterials.2021.121240 [doi]
PST - ppublish
SO  - Biomaterials. 2021 Dec;279:121240. doi: 10.1016/j.biomaterials.2021.121240. Epub 
      2021 Nov 3.