4.1 Article

Cell encapsulated and microenvironment modulating microbeads containing alginate hydrogel system for bone tissue engineering

Journal

PROGRESS IN BIOMATERIALS
Volume 10, Issue 2, Pages 131-150

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s40204-021-00158-3

Keywords

Microenvironment modulating microbead; Microenvironment modulating hydrogel; Stem cells; Tissue engineering; Electrospraying

Funding

  1. Department of Biotechnology, Ministry of Science and Technology, India [BT/RLF/Reentry/21/2013, BT/PR23662/NNT/28/1300/2017, BT/PR24271/TDS/121/40/2017]
  2. Department of Science and Technology, Ministry of Science and Technology, India [SR/NM/-NS-1364/2014(G)]
  3. Department of Science and Technology, Ministry of Science and Technology, Science and Engineering Research Board [SERB-ECR/2015/00040, SB/S3/CE/048/2015]

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The study developed a microenvironment modulating system to fabricate in situ porous hydrogel matrix with two or more distinct tailored microenvironmental niches within microbeads and the hydrogel matrix. Electrosprayed pectin-gelatin blended microbeads and crosslinked alginate hydrogel system were used to tailor microenvironmental niches of encapsulated cells, where two different cells are surrounded by a specific microenvironment, providing a potential technique for heterogeneous tissue regeneration.
Functional tissue regeneration using synthetic biomaterials requires proliferation and heterotypic differentiation of stem/progenitor cells within a specialized heterogeneous (biophysical-biochemical) microenvironment. The current techniques have limitations to develop synthetic hydrogels, mimicking native extracellular matrix porosity along with heterogeneous microenvironmental cues of matrix mechanics, degradability, microstructure and cell-cell interactions. Here, we have developed a microenvironment modulating system to fabricate in situ porous hydrogel matrix with two or more distinct tailored microenvironmental niches within microbeads and the hydrogel matrix for multicellular tissue regeneration. Electrosprayed pectin-gelatin blended microbeads and crosslinked alginate hydrogel system help to tailor microenvironmental niches of encapsulated cells where two different cells are surrounded by a specific microenvironment. The effect of different microenvironmental parameters associated with the microbead/hydrogel matrix was evaluated using human umbilical-cord mesenchymal stem cells (hUCMSCs). The osteogenic differentiation of hUCMSCs in the hydrogel matrix was evaluated for bone tissue regeneration. This will be the first report on microenvironment modulating microbead-hydrogel system to encapsulate two/more types of cells in a hydrogel, where each cell is surrounded with distinct niches for heterogeneous tissue regeneration.

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