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Alg-MR-MS: Dual-crosslinkable microspheres for cell expansion

Biomedical Materials Australia
Overview
Researchers have developed Alginate-methacrylate-RGD microspheres (Alg-MR-MS) that integrate scalable cell expansion and scaffold formation into a single platform. Human adipose-derived stem cells on these microspheres showed a ~5-fold increase in metabolic activity over 7 days, providing a viable path from biomanufacturing to tissue engineering.
In Depth

Key Findings

The Alg-MR-MS system enables the expansion of human adipose-derived stem cells with high viability and strong attachment. Experimental results demonstrate that cells cultured on these microspheres exhibited a ~5-fold increase in metabolic activity over a 7-day period, performing comparably to 2D controls.

Technical Details

The Alg-MR-MS platform utilizes a sequential dual-crosslinking strategy to manage the transition from cell expansion to scaffold stabilization. The technical workflow consists of four primary stages:

  • Fabrication: Microspheres are created via calcium-mediated ionic crosslinking.
  • Expansion: Cells undergo three-dimensional expansion within a microcarrier culture system.
  • Phase Change: Calcium chelation using sodium citrate triggers a controlled phase change, allowing for efficient cell recovery while preserving phenotype and viability.
  • Stabilization: Photocrosslinking is applied to form a stable, cell-laden hydrogel suitable for tissue engineering and bioprinting.

Background and Context

Tissue engineering requires expanding cell populations to clinically relevant numbers, typically achieved using microcarrier-based bioreactors due to their high surface area-to-volume ratio. However, conventional non-dissolvable carriers often require harsh mechanical or enzymatic detachment, which can compromise cell integrity. While some dissolvable carriers exist, most are limited to harvesting and lack the functionality required for downstream tissue engineering applications.

Significance and Outlook

By integrating expansion, dissolution, and structural stabilization into one system, Alg-MR-MS bridges the gap between biomanufacturing and functional tissue engineering. Compared to other dissolvable carriers, this system offers a simplified single-step fabrication process, rapid phase transition, and efficient expansion capabilities, facilitating the delivery of cells into stable scaffolds for implantation.

Source: https://doi.org/10.1088/1748-605x/aeb214

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