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Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks

Nature Materials volume 14, pages 737–744 (2015)Cite this article

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Abstract

Injectable hydrogels can provide a scaffold for in situ tissue regrowth and regeneration, yet gel degradation before tissue reformation limits the gels’ ability to provide physical support. Here, we show that this shortcoming can be circumvented through an injectable, interconnected microporous gel scaffold assembled from annealed microgel building blocks whose chemical and physical properties can be tailored by microfluidic fabrication. In vitro, cells incorporated during scaffold formation proliferated and formed extensive three-dimensional networks within 48 h. In vivo, the scaffolds facilitated cell migration that resulted in rapid cutaneous-tissue regeneration and tissue-structure formation within five days. The combination of microporosity and injectability of these annealed gel scaffolds should enable novel routes to tissue regeneration and formation in vivo.

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Figure 1: Microfluidic generation of microsphere hydrogel building blocks for the creation of microporous annealed particle (MAP) scaffolds.
Figure 2: High-precision fabrication of microgel building blocks allows the creation of defined MAP scaffolds.
Figure 3: MAP scaffolds facilitate 3D cellular network formation and proliferation in vitro.
Figure 4: MAP scaffolds promote fast wound closure in SKH1-Hrhr and Balb/c epidermal mouse models.
Figure 5: MAP scaffolds allow faster tissue regeneration compared with non-porous controls in vivo.
Figure 6: MAP scaffolds elicit a significantly lower immune response than non-porous hydrogels in vivo.

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Acknowledgements

The authors would like to thank A. Vucetic for assistance with gelation-kinetics measurements. This work was partially supported through the US National Institutes of Health Director’s New Innovator Award (1DP2OD007113), NIH RO1HL110592, and the DermSTP Training Grant T32-AR058921.

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Author notes

  1. Donald R. Griffin and Westbrook M. Weaver: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California 90095, USA

    Donald R. Griffin

  2. Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90095, USA

    Westbrook M. Weaver

  3. Division of Dermatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA

    Philip O. Scumpia

  4. Department of Bioengineering, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California 90095, USA

    Dino Di Carlo

  5. Department of Chemical and Biomolecular Engineering, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California 90095, USA

    Tatiana Segura

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  1. Donald R. Griffin
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Contributions

D.R.G. and W.M.W. contributed equally to this manuscript, both in conceptual design, troubleshooting, experimental execution and manuscript writing. P.O.S. performed Day 1 immunological analysis and in vivo interpretation. D.D.C. and T.S. contributed equally to overseeing experimental design and interpretation.

Corresponding authors

Correspondence to Dino Di Carlo or Tatiana Segura.

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Competing interests

The authors have a financial interest in Tempo Therapeutics, which aims to commercialize MAP technology.

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Griffin, D., Weaver, W., Scumpia, P. et al. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nature Mater 14, 737–744 (2015). https://doi.org/10.1038/nmat4294

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