Treffer: Microbubble-Infused Hydrogel Scaffolds With Tunable Porosity for Regenerative-Medicine Applications.
Title:
Microbubble-Infused Hydrogel Scaffolds With Tunable Porosity for Regenerative-Medicine Applications.
Authors:
Ghasemzaie N; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Biomedical Engineering Graduate Program, Toronto Metropolitan University, Toronto, Ontario, Canada., Khader BA; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Department of Chemical and Biological Engineering, American University of Sharjah, Sharjah, UAE., Tran S; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Biomedical Engineering Graduate Program, Toronto Metropolitan University, Toronto, Ontario, Canada., Khan S; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Department of Electrical, Computer, and Biomedical Engineering, Toronto Metropolitan University, Toronto, Ontario, Canada., Rahman OM; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Biomedical Engineering Graduate Program, Toronto Metropolitan University, Toronto, Ontario, Canada., Hwang DK; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Department of Chemical Engineering, Toronto, Metropolitan University, Toronto, Ontario, Canada., Kolios MC; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Department of Physics, Toronto Metropolitan University, Toronto, Ontario, Canada., Tsai SSH; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.; Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Ontario, Canada.; Biomedical Engineering Graduate Program, Toronto Metropolitan University, Toronto, Ontario, Canada.; Department of Mechanical, Industrial, and Mechatronics Engineering, Toronto, Metropolitan University, Toronto, Ontario, Canada.
Source:
Journal of biomedical materials research. Part B, Applied biomaterials [J Biomed Mater Res B Appl Biomater] 2026 Jan; Vol. 114 (1), pp. e70022.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101234238 Publication Model: Print Cited Medium: Internet ISSN: 1552-4981 (Electronic) Linking ISSN: 15524973 NLM ISO Abbreviation: J Biomed Mater Res B Appl Biomater Subsets: MEDLINE
Imprint Name(s):
Original Publication: Hoboken, NJ : John Wiley & Sons, c2003-
MeSH Terms:
Hydrogels*/chemistry , Tissue Scaffolds*/chemistry , Microbubbles* , Regenerative Medicine*, Porosity ; Alginates/chemistry ; Polyethylene Glycols/chemistry ; Gelatin/chemistry ; Humans ; Methacrylates/chemistry ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/cytology ; Tissue Engineering ; Animals
References:
N. Annabi, J. W. Nichol, X. Zhong, et al., “Controlling the Porosity and Microarchitecture of Hydrogels for Tissue Engineering,” Tissue Engineering. Part B, Reviews 16, no. 4 (2010): 371–383.
V. Guarino, F. Causa, A. Salerno, L. Ambrosio, and P. A. Netti, “Design and Manufacture of Microporous Polymeric Materials With Hierarchal Complex Structure for Biomedical Application,” Materials Science and Technology 24, no. 9 (2008): 1111–1117.
F. Mukasheva, L. Adilova, A. Dyussenbinov, B. Yernaimanova, M. Abilev, and D. Akilbekova, “Optimizing Scaffold Pore Size for Tissue Engineering: Insights Across Various Tissue Types,” Frontiers in Bioengineering and Biotechnology 12 (2024): 1444986.
K. M. Jurczak, R. Zhang, W. L. Hinrichs, et al., “Porous Polytrimethylenecarbonate Scaffolds: Design Considerations and Porosity Modulation Techniques,” Materials & Design 250, no. 113588 (2025): 113588.
T. Nayaju, D. Shrestha, K. Kang, B. Maharjan, and C. H. Park, “Reconstructed Three‐Dimensional Structure of Gas‐Foamed Polycaprolactone/Cellulose Nanofibrous Scaffold for Biomedical Applications,” International Journal of Biological Macromolecules 285, no. 138253 (2024): 138253.
Z. Wang, J. Xu, J. Zhu, et al., “Osteochondral Tissue Engineering: Scaffold Materials, Fabrication Techniques and Applications,” Biotechnology Journal 20, no. 1 (2025): e202400699.
S. A. Bencherif, R. Warren Sands, O. A. Ali, et al., “Injectable Cryogel‐Based Whole‐Cell Cancer Vaccines,” Nature Communications 6, no. 1 (2015): 7556.
F. J. Maksoud, M. F. de la Velázquez Paz, A. J. Hann, et al., “Porous Biomaterials for Tissue Engineering: A Review,” Journal of Materials Chemistry. B, Materials for Biology and Medicine 10, no. 40 (2022): 8111–8165.
J. Esmaeili, F. S. Rezaei, F. M. Beram, and A. Barati, “Integration of Microbubbles With Biomaterials in Tissue Engineering for Pharmaceutical Purposes,” Heliyon 6, no. 6 (2020): e04189.
E. G. Lima, K. M. Durney, S. R. Sirsi, et al., “Microbubbles as Biocompatible Porogens for Hydrogel Scaffolds,” Acta Biomaterialia 8, no. 12 (2012): 4334–4341.
C. Bayram, X. Jiang, M. Gultekinoglu, O. Sukru, K. Ulubayram, and M. Edirisinghe, “Biofabrication of Gelatin Tissue Scaffolds With Uniform Pore Size via Microbubble Assembly,” Macromolecular Materials and Engineering 304, no. 11 (2019): 1900394.
E. B. Demiray, T. Sezgin Arslan, B. Derkus, and Y. E. Arslan, “A Facile Strategy for Preparing Flexible and Porous Hydrogel‐Based Scaffolds From Silk Sericin/Wool Keratin by In Situ Bubble‐Forming for Muscle Tissue Engineering Applications,” Macromolecular Bioscience 25, no. 2 (2025): e2400362.
S. Van Vlierberghe, P. Dubruel, and E. Schacht, “Biopolymerbased Hydrogels as Scaffolds for Tissue Engineering Applications: A Review,” Biomacromolecules 12, no. 5 (2011): 1387–1408.
N. Huebsch, E. Lippens, K. Lee, et al., “Matrix Elasticity of Void‐Forming Hydrogels Controls Transplanted‐Stem‐Cell‐Mediated Bone Formation,” Nature Materials 14, no. 12 (2015): 1269–1277.
X. Lu, H. Jin, C. Quesada, et al., “Spatially‐Directed Cell Migration in Acoustically Responsive Scaffolds Through the Controlled Delivery of Basic Fibroblast Growth Factor,” Acta Biomaterialia 113 (2020): 217–227.
C. Counil, E. Abenojar, R. Perera, and A. A. Exner, “Extrusion: A New Method for Rapid Formulation of High‐Yield Monodisperse Nanobubbles,” Small (Weinheim an der Bergstrasse, Germany) 18, no. 24 (2022): e2200810.
J. J. Kwan and M. A. Borden, “Lipid Monolayer Collapse and Microbubble Stability,” Advances in Colloid and Interface Science 183‐184 (2012): 82–99.
N. Ghasemzaie, M. Jeyhani, K. Joshi, W. L. Lee, and S. S. H. Tsai, “ATPSpin: A Single Microfluidic Platform That Produces Diversified ATPS‐Alginate Microfibers,” ACS Biomaterials Science & Engineering 10, no. 6 (2024): 3896–3908.
O. M. Rahman, R. Tarantino, S. D. Waldman, and D. K. Hwang, “Single‐Step Fabrication of V‐Shaped Polymeric Microwells to Enhance Cancer Spheroid Formation,” ACS Biomaterials Science & Engineering 11, no. 3 (2025): 1857–1868.
B. A. Khader, C. Volpe, S. D. Waldman, and D. K. Hwang, “Highly Elastic Bioactive bR‐GelMA Micro‐Particles: Synthesis and Precise Micro‐Fabrication via Stop‐Flow Lithography,” Biomedical Materials (Bristol, England) 20 (2025): 035003.
J. Schindelin, I. Arganda‐Carreras, F. Erwin, et al., “Fiji: An Open‐Source Platform for Biological‐Image Analysis,” Nature Methods 9, no. 7 (2012): 676–682.
A. S. Sergeeva, D. A. Gorin, and D. V. Volodkin, “In‐Situ Assembly of Ca‐Alginate Gels With Controlled Pore Loading/Release Capability,” Langmuir 31, no. 39 (2015): 10813–10821.
B. A. Nerger, K. Kashyap, B. T. Deveney, et al., “Tuning Porosity of Macroporous Hydrogels Enables Rapid Rates of Stress Relaxation and Promotes Cell Expansion and Migration,” Proceedings of the National Academy of Sciences of the United States of America 121, no. 45 (2024): e2410806121.
M. Yan, L. Wang, Y. Wu, L. Wang, and Y. Lu, “Three‐Dimensional Highly Porous Hydrogel Scaffold for Neural Circuit Dissection and Modulation,” Acta Biomaterialia 157 (2023): 252–262.
H. Li, K. S. Iyer, L. Bao, Z. Jiali, and J. J. Li, “Advances in the Development of Granular Microporous Injectable Hydrogels With Nonspherical Microgels and Their Applications in Tissue Regeneration,” Advanced Healthcare Materials 13, no. 25 (2024): e2301597.
J. Chen and K. Park, “Synthesis and Characterization of Superporous Hydrogel Composites,” Journal of Controlled Release 65, no. 1–2 (2000): 73–82.
K. Webb, V. Hlady, and P. A. Tresco, “Relative Importance of Surface Wettability and Charged Functional Groups on NIH 3T3 Fibroblast Attachment, Spreading, and Cytoskeletal Organization,” Journal of Biomedical Materials Research 41, no. 3 (1998): 422–430.
X. Lin, X. Zhao, C. Xu, L. Wang, and Y. Xia, “Progress in the Mechanical Enhancement of Hydrogels: Fabrication Strategies and Underlying Mechanisms,” Journal of Polymer Science 60, no. 17 (2022): 2525–2542.
J. H. Park, B. G. Chung, W. G. Lee, et al., “Microporous Cell‐Laden Hydrogels for Engineered Tissue Constructs,” Biotechnology and Bioengineering 106, no. 1 (2010): 138–148.
K. Zhang, W. Feng, and C. Jin, “Protocol Efficiently Measuring the Swelling Rate of Hydrogels,” MethodsX 7 (2020): 100779.
A. R. Hudson, D. J. Shiwarski, A. J. Kramer, and A. W. Feinberg, “Enhancing Viability in Static and Perfused 3D Tissue Constructs Using Sacrificial Gelatin Microparticles,” ACS Biomaterials Science & Engineering 11, no. 5 (2025): 2888–2897.
S. Erikci, N. van den Bergh, and H. Boehm, “Kinetic and Mechanistic Release Studies on Hyaluronan Hydrogels for Their Potential Use as a pH‐Responsive Drug Delivery Device,” Gels 10, no. 11 (2024): 731.
A. Kedzierski, S. Kheirabadi, A. Jaberi, et al., “Engineering the Hierarchical Porosity of Granular Hydrogel Scaffolds Using Porous Microgels to Improve Cell Recruitment and Tissue Integration,” Advanced Functional Materials 35, no. 12 (2025): 2417704.
E. C. Novosel, C. Kleinhans, and P. J. Kluger, “Vascularization Is the Key Challenge in Tissue Engineering,” Advanced Drug Delivery Reviews 63, no. 45 (2011): 300–311.
N. F. Truong, E. Kurt, N. Tahmizyan, et al., “Microporous Annealed Particle Hydrogel Stiffness, Void Space Size, and Adhesion Properties Impact Cell Proliferation, Cell Spreading, and Gene Transfer,” Acta Biomaterialia 94 (2019): 160–172.
K. Kim, B. Yoon, J. Lee, G. Kim, and M. H. Park, “NIR‐Responsive Microbubble Delivery Platforms for Controlled Drug Release in Cancer Therapy,” Materials (Basel, Switzerland) 18, no. 12 (2025): 2725.
A. Ignee, N. S. S. Atkinson, G. Schuessler, and C. F. Dietrich, “Ultrasound Contrast Agents,” Endoscopic Ultrasound 5, no. 6 (2016): 355–362.
Q. L. Loh and C. Choong, “Three‐Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size,” Tissue Engineering. Part B, Reviews 19, no. 6 (2013): 485–502.
V. Guarino, F. Causa, A. Salerno, L. Ambrosio, and P. A. Netti, “Design and Manufacture of Microporous Polymeric Materials With Hierarchal Complex Structure for Biomedical Application,” Materials Science and Technology 24, no. 9 (2008): 1111–1117.
F. Mukasheva, L. Adilova, A. Dyussenbinov, B. Yernaimanova, M. Abilev, and D. Akilbekova, “Optimizing Scaffold Pore Size for Tissue Engineering: Insights Across Various Tissue Types,” Frontiers in Bioengineering and Biotechnology 12 (2024): 1444986.
K. M. Jurczak, R. Zhang, W. L. Hinrichs, et al., “Porous Polytrimethylenecarbonate Scaffolds: Design Considerations and Porosity Modulation Techniques,” Materials & Design 250, no. 113588 (2025): 113588.
T. Nayaju, D. Shrestha, K. Kang, B. Maharjan, and C. H. Park, “Reconstructed Three‐Dimensional Structure of Gas‐Foamed Polycaprolactone/Cellulose Nanofibrous Scaffold for Biomedical Applications,” International Journal of Biological Macromolecules 285, no. 138253 (2024): 138253.
Z. Wang, J. Xu, J. Zhu, et al., “Osteochondral Tissue Engineering: Scaffold Materials, Fabrication Techniques and Applications,” Biotechnology Journal 20, no. 1 (2025): e202400699.
S. A. Bencherif, R. Warren Sands, O. A. Ali, et al., “Injectable Cryogel‐Based Whole‐Cell Cancer Vaccines,” Nature Communications 6, no. 1 (2015): 7556.
F. J. Maksoud, M. F. de la Velázquez Paz, A. J. Hann, et al., “Porous Biomaterials for Tissue Engineering: A Review,” Journal of Materials Chemistry. B, Materials for Biology and Medicine 10, no. 40 (2022): 8111–8165.
J. Esmaeili, F. S. Rezaei, F. M. Beram, and A. Barati, “Integration of Microbubbles With Biomaterials in Tissue Engineering for Pharmaceutical Purposes,” Heliyon 6, no. 6 (2020): e04189.
E. G. Lima, K. M. Durney, S. R. Sirsi, et al., “Microbubbles as Biocompatible Porogens for Hydrogel Scaffolds,” Acta Biomaterialia 8, no. 12 (2012): 4334–4341.
C. Bayram, X. Jiang, M. Gultekinoglu, O. Sukru, K. Ulubayram, and M. Edirisinghe, “Biofabrication of Gelatin Tissue Scaffolds With Uniform Pore Size via Microbubble Assembly,” Macromolecular Materials and Engineering 304, no. 11 (2019): 1900394.
E. B. Demiray, T. Sezgin Arslan, B. Derkus, and Y. E. Arslan, “A Facile Strategy for Preparing Flexible and Porous Hydrogel‐Based Scaffolds From Silk Sericin/Wool Keratin by In Situ Bubble‐Forming for Muscle Tissue Engineering Applications,” Macromolecular Bioscience 25, no. 2 (2025): e2400362.
S. Van Vlierberghe, P. Dubruel, and E. Schacht, “Biopolymerbased Hydrogels as Scaffolds for Tissue Engineering Applications: A Review,” Biomacromolecules 12, no. 5 (2011): 1387–1408.
N. Huebsch, E. Lippens, K. Lee, et al., “Matrix Elasticity of Void‐Forming Hydrogels Controls Transplanted‐Stem‐Cell‐Mediated Bone Formation,” Nature Materials 14, no. 12 (2015): 1269–1277.
X. Lu, H. Jin, C. Quesada, et al., “Spatially‐Directed Cell Migration in Acoustically Responsive Scaffolds Through the Controlled Delivery of Basic Fibroblast Growth Factor,” Acta Biomaterialia 113 (2020): 217–227.
C. Counil, E. Abenojar, R. Perera, and A. A. Exner, “Extrusion: A New Method for Rapid Formulation of High‐Yield Monodisperse Nanobubbles,” Small (Weinheim an der Bergstrasse, Germany) 18, no. 24 (2022): e2200810.
J. J. Kwan and M. A. Borden, “Lipid Monolayer Collapse and Microbubble Stability,” Advances in Colloid and Interface Science 183‐184 (2012): 82–99.
N. Ghasemzaie, M. Jeyhani, K. Joshi, W. L. Lee, and S. S. H. Tsai, “ATPSpin: A Single Microfluidic Platform That Produces Diversified ATPS‐Alginate Microfibers,” ACS Biomaterials Science & Engineering 10, no. 6 (2024): 3896–3908.
O. M. Rahman, R. Tarantino, S. D. Waldman, and D. K. Hwang, “Single‐Step Fabrication of V‐Shaped Polymeric Microwells to Enhance Cancer Spheroid Formation,” ACS Biomaterials Science & Engineering 11, no. 3 (2025): 1857–1868.
B. A. Khader, C. Volpe, S. D. Waldman, and D. K. Hwang, “Highly Elastic Bioactive bR‐GelMA Micro‐Particles: Synthesis and Precise Micro‐Fabrication via Stop‐Flow Lithography,” Biomedical Materials (Bristol, England) 20 (2025): 035003.
J. Schindelin, I. Arganda‐Carreras, F. Erwin, et al., “Fiji: An Open‐Source Platform for Biological‐Image Analysis,” Nature Methods 9, no. 7 (2012): 676–682.
A. S. Sergeeva, D. A. Gorin, and D. V. Volodkin, “In‐Situ Assembly of Ca‐Alginate Gels With Controlled Pore Loading/Release Capability,” Langmuir 31, no. 39 (2015): 10813–10821.
B. A. Nerger, K. Kashyap, B. T. Deveney, et al., “Tuning Porosity of Macroporous Hydrogels Enables Rapid Rates of Stress Relaxation and Promotes Cell Expansion and Migration,” Proceedings of the National Academy of Sciences of the United States of America 121, no. 45 (2024): e2410806121.
M. Yan, L. Wang, Y. Wu, L. Wang, and Y. Lu, “Three‐Dimensional Highly Porous Hydrogel Scaffold for Neural Circuit Dissection and Modulation,” Acta Biomaterialia 157 (2023): 252–262.
H. Li, K. S. Iyer, L. Bao, Z. Jiali, and J. J. Li, “Advances in the Development of Granular Microporous Injectable Hydrogels With Nonspherical Microgels and Their Applications in Tissue Regeneration,” Advanced Healthcare Materials 13, no. 25 (2024): e2301597.
J. Chen and K. Park, “Synthesis and Characterization of Superporous Hydrogel Composites,” Journal of Controlled Release 65, no. 1–2 (2000): 73–82.
K. Webb, V. Hlady, and P. A. Tresco, “Relative Importance of Surface Wettability and Charged Functional Groups on NIH 3T3 Fibroblast Attachment, Spreading, and Cytoskeletal Organization,” Journal of Biomedical Materials Research 41, no. 3 (1998): 422–430.
X. Lin, X. Zhao, C. Xu, L. Wang, and Y. Xia, “Progress in the Mechanical Enhancement of Hydrogels: Fabrication Strategies and Underlying Mechanisms,” Journal of Polymer Science 60, no. 17 (2022): 2525–2542.
J. H. Park, B. G. Chung, W. G. Lee, et al., “Microporous Cell‐Laden Hydrogels for Engineered Tissue Constructs,” Biotechnology and Bioengineering 106, no. 1 (2010): 138–148.
K. Zhang, W. Feng, and C. Jin, “Protocol Efficiently Measuring the Swelling Rate of Hydrogels,” MethodsX 7 (2020): 100779.
A. R. Hudson, D. J. Shiwarski, A. J. Kramer, and A. W. Feinberg, “Enhancing Viability in Static and Perfused 3D Tissue Constructs Using Sacrificial Gelatin Microparticles,” ACS Biomaterials Science & Engineering 11, no. 5 (2025): 2888–2897.
S. Erikci, N. van den Bergh, and H. Boehm, “Kinetic and Mechanistic Release Studies on Hyaluronan Hydrogels for Their Potential Use as a pH‐Responsive Drug Delivery Device,” Gels 10, no. 11 (2024): 731.
A. Kedzierski, S. Kheirabadi, A. Jaberi, et al., “Engineering the Hierarchical Porosity of Granular Hydrogel Scaffolds Using Porous Microgels to Improve Cell Recruitment and Tissue Integration,” Advanced Functional Materials 35, no. 12 (2025): 2417704.
E. C. Novosel, C. Kleinhans, and P. J. Kluger, “Vascularization Is the Key Challenge in Tissue Engineering,” Advanced Drug Delivery Reviews 63, no. 45 (2011): 300–311.
N. F. Truong, E. Kurt, N. Tahmizyan, et al., “Microporous Annealed Particle Hydrogel Stiffness, Void Space Size, and Adhesion Properties Impact Cell Proliferation, Cell Spreading, and Gene Transfer,” Acta Biomaterialia 94 (2019): 160–172.
K. Kim, B. Yoon, J. Lee, G. Kim, and M. H. Park, “NIR‐Responsive Microbubble Delivery Platforms for Controlled Drug Release in Cancer Therapy,” Materials (Basel, Switzerland) 18, no. 12 (2025): 2725.
A. Ignee, N. S. S. Atkinson, G. Schuessler, and C. F. Dietrich, “Ultrasound Contrast Agents,” Endoscopic Ultrasound 5, no. 6 (2016): 355–362.
Q. L. Loh and C. Choong, “Three‐Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size,” Tissue Engineering. Part B, Reviews 19, no. 6 (2013): 485–502.
Grant Information:
202303PJT-496149-BE2ABAF-244211 The Canadian Institutes of Health Research (CIHR) Project Grants Program; RGPIN-2025-04857 Canadian Natural Sciences and Engineering Research Council (NSERC) Discovery Grants Program; 36687 Canada Foundation for Innovation; 36442 Canada Foundation for Innovation; Ontario Research Fund (ORF); Toronto Metropolitan University
Contributed Indexing:
Keywords: GelMA; cytocompatibility; hydrogel scaffolds; mesenchymal stem cells; microbubbles; regenerative medicine; tunable porosity
Substance Nomenclature:
0 (Hydrogels)
0 (Alginates)
3WJQ0SDW1A (Polyethylene Glycols)
0 (poly(ethylene glycol)diacrylate)
9000-70-8 (Gelatin)
0 (Methacrylates)
0 (Alginates)
3WJQ0SDW1A (Polyethylene Glycols)
0 (poly(ethylene glycol)diacrylate)
9000-70-8 (Gelatin)
0 (Methacrylates)
Entry Date(s):
Date Created: 20260108 Date Completed: 20260108 Latest Revision: 20260108
Update Code:
20260108
DOI:
10.1002/jbmb.70022
PMID:
41503723
Database:
MEDLINE
Weitere Informationen
Tissue-engineering scaffolds require interconnected porous networks to support cell infiltration, nutrient diffusion, and waste removal. Conventional methods to introduce porosity-such as particulate leaching, gas foaming, and freeze-drying-can leave cytotoxic residues. We propose a scalable, cytocompatible approach to tune hydrogel porosity using lipid-shelled gas microbubbles as a transient porogen. In this study, we demonstrate that lipid-shelled microbubbles can be incorporated into alginate, poly(ethylene glycol) diacrylate (PEGDA), or gelatin methacrylate (GelMA) precursors, and subsequently expanded post-gelation with mild heat or vacuum to yield controlled porosity. In alginate fibers, the vacuum expansion of embedded microbubbles increased the swelling capacity by approximately 74% relative to nonporous control, without reducing compressive strength. Porous PEGDA hydrogels showed faster degradation (approximately 40% reduction in degradation time) and a lower compressive modulus compared to the dense PEGDA control, reflecting a tunable trade-off between porosity and stiffness. Unlike traditional porogen-based or 3D-printing techniques, this microbubble method requires no toxic additives or specialized equipment and is compatible with both ionic (alginate) and photo-crosslinked (PEGDA, GelMA) systems. We further demonstrate integration of this approach with a microfluidic fiber production platform. We validate that porosity modulation via microbubbles does not adversely affect the viability of mesenchymal stem cells on GelMA hydrogels. Overall, this work establishes a broadly applicable and easily scaled strategy in which porosity can be tuned post-gelation with simple triggers (heat or vacuum), enabling application-specific control of nutrient transport, degradation, and mechanics across multiple biomaterials.
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