Synergistic effect of Hypoxic Conditioning and Cell‐Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration

Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell-tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long-term manner. Cell-tethering colloidal hydrogels that are composed of tyramine-conjugated gelatin prevent cells from egressing through on-cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host-implant interactions. Oxygenating microparticles encapsulated in tyramine-conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic-conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti-inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC-tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.

Authors

Institutions

Publication Details

Journal
Advanced Materials
Published
2024-10-09
DOI
https://doi.org/10.1002/adma.202408488
Citations
13
Primary Topic
3D Printing in Biomedical Research
Type
article
Field-Weighted Citation Impact
2.40

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Synergistic effect of Hypoxic Conditioning and Cell‐Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration

Cholong Choi, Violeta Carvalho, Anurag Jamaiyar, Da‐Seul Kim et al.
13 citations
Advanced Materials
3D Printing in Biomedical Research
2.40
article

Synergistic effect of Hypoxic Conditioning and Cell‐Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration

Cholong Choi, Violeta Carvalho, Anurag Jamaiyar, Da‐Seul Kim, Nicole Bassous, Jae Seo Lee, Su Ryon Shin, Mark W. Feinberg, Mohammad Asif Hussain, Abdulhameed F. Alkhateeb, Senhorinha Teixeira, Jeroen Leijten, Nélson Rodrigues, Myung Chul Lee, Seong-Soo Kim, Jeong Wook Seo, Andrea Donaxi Madrigal‐Salazar, Javier Alejandro Lozano Soto, Montserrat Legorreta Gonzalez, Winona Wu, Tania Carolina Acevedo Durán
article en
13 citations

Abstract

Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell-tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long-term manner. Cell-tethering colloidal hydrogels that are composed of tyramine-conjugated gelatin prevent cells from egressing through on-cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host-implant interactions. Oxygenating microparticles encapsulated in tyramine-conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic-conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti-inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC-tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.

Advanced MaterialsVol. 37(3)
Brigham and Women's Hospital (US), Beth Israel Deaconess Medical Center (US), Harvard University (US), King Abdulaziz University (SA), Massachusetts General Hospital (US), Lusíada University of Porto (PT), Korea Institute of Science and Technology (KR), University of Twente (NL), University of Minho (PT)
Foundation for the National Institutes of Health, American Heart Association, National Research Foundation, Ministry of Education, Korea Institute of Science and Technology, Korea Health Industry Development Institute, National Research Foundation of Korea, King Abdulaziz University, Fulbright Portugal, Foundation for Science and Technology, National Institutes of Health, Deanship of Scientific Research, Prince Sattam bin Abdulaziz University, Fundação para a Ciência e a Tecnologia
Openalex Percentile: Top 11%
3D Printing in Biomedical Research
2.40
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.