Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads

Amir Sheikhi, Joseph de Rutte, Reihaneh Haghniaz, Outman Akouissi, Alireza Sohrabi, Dino Di Carlo, Ali Khademhosseini

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Naturally-derived proteins, such as collagen, elastin, fibroin, and gelatin (denatured collagen) hold a remarkable promise for tissue engineering and regenerative medicine. Gelatin methacryloyl (GelMA), synthesized from the methacryloyl modification of gelatin, mimicking the structure of extracellular matrix, has widely been used as a universal multi-responsive scaffold for a broad spectrum of applications, spanning from cell therapy to bioprinting and organoid development. Despite the widespread applications of GelMA, coupled stiffness and porosity has inhibited its applications in 3D cellular engineering wherein a stiff scaffold with large pores is demanded (e.g., at concentrations >10 wt%). Taking advantage of the orthogonal thermo-chemical responsivity of GelMA, we have developed microfluidic-assisted annealable GelMA beads, that are first stabilized by temperature-mediated physical crosslinking, flowed to form a scaffold structure, and then chemically annealed using light to fabricate novel bead-based 3D GelMA scaffolds with high mechanical resilience. We show how beaded GelMA (B-GelMA) provides a self-standing microporous environment with an orthogonal void fraction and stiffness, promoting cell adhesion, proliferation, and rapid 3D seeding at a high polymer concentration (∼20 wt%) that would otherwise be impossible for bulk GelMA. B-GelMA, decorated with methacryloyl and arginylglycylaspartic acid (RGD) peptide motifs, does not require additional functionalization for annealing and cell adhesion, providing a versatile biorthogonal platform with orthogonal stiffness and porosity for a myriad of biomedical applications. This technology provides a universal method to convert polymeric materials with orthogonal physico-chemical responsivity to modular platforms, opening a new horizon for converting bulk hydrogels to beaded hydrogels (B-hydrogels) with decoupled porosity and stiffness.

Original languageEnglish (US)
Pages (from-to)560-568
Number of pages9
JournalBiomaterials
Volume192
DOIs
StatePublished - Feb 1 2019

Fingerprint

Hydrogels
Microfluidics
Gelatin
Microspheres
Scaffolds
Stiffness
Proteins
Porosity
Cell adhesion
Collagen
Elastin
Forms (concrete)
Void fraction
Polymers
Tissue engineering
Crosslinking
Peptides
Cell Adhesion
Bioprinting
Annealing

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Sheikhi, A., de Rutte, J., Haghniaz, R., Akouissi, O., Sohrabi, A., Di Carlo, D., & Khademhosseini, A. (2019). Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads. Biomaterials, 192, 560-568. https://doi.org/10.1016/j.biomaterials.2018.10.040
Sheikhi, Amir ; de Rutte, Joseph ; Haghniaz, Reihaneh ; Akouissi, Outman ; Sohrabi, Alireza ; Di Carlo, Dino ; Khademhosseini, Ali. / Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads. In: Biomaterials. 2019 ; Vol. 192. pp. 560-568.
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Sheikhi, A, de Rutte, J, Haghniaz, R, Akouissi, O, Sohrabi, A, Di Carlo, D & Khademhosseini, A 2019, 'Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads', Biomaterials, vol. 192, pp. 560-568. https://doi.org/10.1016/j.biomaterials.2018.10.040

Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads. / Sheikhi, Amir; de Rutte, Joseph; Haghniaz, Reihaneh; Akouissi, Outman; Sohrabi, Alireza; Di Carlo, Dino; Khademhosseini, Ali.

In: Biomaterials, Vol. 192, 01.02.2019, p. 560-568.

Research output: Contribution to journalArticle

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T1 - Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads

AU - Sheikhi, Amir

AU - de Rutte, Joseph

AU - Haghniaz, Reihaneh

AU - Akouissi, Outman

AU - Sohrabi, Alireza

AU - Di Carlo, Dino

AU - Khademhosseini, Ali

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N2 - Naturally-derived proteins, such as collagen, elastin, fibroin, and gelatin (denatured collagen) hold a remarkable promise for tissue engineering and regenerative medicine. Gelatin methacryloyl (GelMA), synthesized from the methacryloyl modification of gelatin, mimicking the structure of extracellular matrix, has widely been used as a universal multi-responsive scaffold for a broad spectrum of applications, spanning from cell therapy to bioprinting and organoid development. Despite the widespread applications of GelMA, coupled stiffness and porosity has inhibited its applications in 3D cellular engineering wherein a stiff scaffold with large pores is demanded (e.g., at concentrations >10 wt%). Taking advantage of the orthogonal thermo-chemical responsivity of GelMA, we have developed microfluidic-assisted annealable GelMA beads, that are first stabilized by temperature-mediated physical crosslinking, flowed to form a scaffold structure, and then chemically annealed using light to fabricate novel bead-based 3D GelMA scaffolds with high mechanical resilience. We show how beaded GelMA (B-GelMA) provides a self-standing microporous environment with an orthogonal void fraction and stiffness, promoting cell adhesion, proliferation, and rapid 3D seeding at a high polymer concentration (∼20 wt%) that would otherwise be impossible for bulk GelMA. B-GelMA, decorated with methacryloyl and arginylglycylaspartic acid (RGD) peptide motifs, does not require additional functionalization for annealing and cell adhesion, providing a versatile biorthogonal platform with orthogonal stiffness and porosity for a myriad of biomedical applications. This technology provides a universal method to convert polymeric materials with orthogonal physico-chemical responsivity to modular platforms, opening a new horizon for converting bulk hydrogels to beaded hydrogels (B-hydrogels) with decoupled porosity and stiffness.

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