PMID- 36533728
OWN - NLM
STAT- MEDLINE
DCOM- 20221220
LR  - 20231120
IS  - 1758-5090 (Electronic)
IS  - 1758-5082 (Print)
IS  - 1758-5082 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Dec 19
TI  - 3D-bioprinted, phototunable hydrogel models for studying adventitial fibroblast 
      activation in pulmonary arterial hypertension.
LID - 10.1088/1758-5090/aca8cf [doi]
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease of the lung 
      vasculature, characterized by elevated pulmonary blood pressure, remodeling of 
      the pulmonary arteries, and ultimately right ventricular failure. Therapeutic 
      interventions for PAH are limited in part by the lack ofin vitroscreening 
      platforms that accurately reproduce dynamic arterial wall mechanical properties. 
      Here we present a 3D-bioprinted model of the pulmonary arterial adventitia 
      comprised of a phototunable poly(ethylene glycol) alpha methacrylate 
      (PEG-alphaMA)-based hydrogel and primary human pulmonary artery adventitia 
      fibroblasts (HPAAFs). This unique biomaterial emulates PAH pathogenesisin 
      vitrothrough a two-step polymerization reaction. First, PEG-alphaMA macromer was 
      crosslinked off-stoichiometry by 3D bioprinting an acidic bioink solution into a 
      basic gelatin support bath initiating a base-catalyzed thiol-ene reaction with 
      synthetic and biodegradable crosslinkers. Then, matrix stiffening was induced by 
      photoinitiated homopolymerization of unreacted alphaMA end groups. A design of 
      experiments approach produced a hydrogel platform that exhibited an initial 
      elastic modulus (E) within the range of healthy pulmonary arterial tissue (E= 4.7 
      +/- 0.09 kPa) that was stiffened to the pathologic range of hypertensive tissue (E= 
      12.8 +/- 0.47 kPa) and supported cellular proliferation over time. A higher 
      percentage of HPAAFs cultured in stiffened hydrogels expressed the fibrotic 
      marker alpha-smooth muscle actin than cells in soft hydrogels (88 +/- 2% versus 65 
      +/- 4%). Likewise, a greater percentage of HPAAFs were positive for the 
      proliferation marker 5-ethynyl-2'-deoxyuridine (EdU) in stiffened models (66 +/- 
      6%) compared to soft (39 +/- 6%). These results demonstrate that 3D-bioprinted, 
      phototunable models of pulmonary artery adventitia are a tool that enable 
      investigation of fibrotic pathogenesisin vitro.
CI  - (c) 2022 IOP Publishing Ltd.
FAU - Davis-Hall, Duncan
AU  - Davis-Hall D
AUID- ORCID: 0000-0003-1280-8018
AD  - Department of Bioengineering, University of Colorado Denver | Anschutz Medical 
      Campus, Aurora, CO, United States of America.
FAU - Thomas, Emily
AU  - Thomas E
AD  - Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 
      United States of America.
FAU - Pena, Brisa
AU  - Pena B
AD  - Department of Bioengineering, University of Colorado Denver | Anschutz Medical 
      Campus, Aurora, CO, United States of America.
AD  - CU-Cardiovascular Institute, University of Colorado Anschutz Medical Campus, 
      Aurora, CO, United States of America.
FAU - Magin, Chelsea M
AU  - Magin CM
AUID- ORCID: 0000-0002-6988-8584
AD  - Department of Bioengineering, University of Colorado Denver | Anschutz Medical 
      Campus, Aurora, CO, United States of America.
AD  - Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, 
      CO, United States of America.
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of 
      Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United 
      States of America.
LA  - eng
GR  - R21 CA252172/CA/NCI NIH HHS/United States
GR  - K25 HL148386/HL/NHLBI NIH HHS/United States
GR  - R01 HL080396/HL/NHLBI NIH HHS/United States
GR  - R01 HL153096/HL/NHLBI NIH HHS/United States
GR  - F31 HL151122/HL/NHLBI NIH HHS/United States
GR  - T32 HL072738/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221219
PL  - England
TA  - Biofabrication
JT  - Biofabrication
JID - 101521964
RN  - 0 (Hydrogels)
RN  - 0 (polyethylene glycol methacrylate)
SB  - IM
MH  - Humans
MH  - Hydrogels/pharmacology
MH  - Adventitia
MH  - *Pulmonary Arterial Hypertension
MH  - *Hypertension, Pulmonary
MH  - *Bioprinting
MH  - Fibroblasts
PMC - PMC9933849
MID - NIHMS1872456
OTO - NOTNLM
OT  - 3D bioprinting
OT  - biomaterials
OT  - blood vessels
OT  - in vitro model
OT  - phototunable hydrogels
OT  - pulmonary arterial hypertension
OT  - pulmonary artery adventitia fibroblasts
COIS- Conflict of interest Chelsea Magin reports a relationship with Boulder iQ that 
      includes consulting fees. Chelsea Magin has Patent #PCT/US2019/012722 pending to 
      University of Colorado. All other authors, Duncan Davis-Hall, Emily Thomas, and 
      Brisa Pena, 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- 2022/12/20 06:00
MHDA- 2022/12/21 06:00
PMCR- 2023/11/19
CRDT- 2022/12/19 07:42
PHST- 2022/03/23 00:00 [received]
PHST- 2022/12/05 00:00 [accepted]
PHST- 2022/12/19 07:42 [entrez]
PHST- 2022/12/20 06:00 [pubmed]
PHST- 2022/12/21 06:00 [medline]
PHST- 2023/11/19 00:00 [pmc-release]
AID - 10.1088/1758-5090/aca8cf [doi]
PST - epublish
SO  - Biofabrication. 2022 Dec 19;15(1):10.1088/1758-5090/aca8cf. doi: 
      10.1088/1758-5090/aca8cf.