Scientific article
OA Policy
English

Hyaluronan-based hydrogel delivering glucose to mesenchymal stem cells intended to treat osteoarthritis

Published inInternational journal of pharmaceutics, vol. 657, 124139
Publication date2024-05-25
First online date2024-05-10
Abstract

Mesenchymal stem cell (MSC) therapy shows promise in regenerative medicine. For osteoarthritis (OA), MSCs delivered to the joint have a temporal window in which they can secrete growth factors and extracellular matrix molecules, contributing to cartilage regeneration and cell proliferation. However, upon injection in the non-vascularized joint, MSCs lacking energy supply, starve and die too quickly to efficiently deliver enough of these factors. To feed injected MSCs, we developed a hyaluronic acid (HA) derivative, where glucose is covalently bound to hyaluronic acid. To achieve this, the glucose moiety in 4-aminophenyl-β-D-glucopyranoside was linked to the HA backbone through amidation. The hydrogel was able to deliver glucose in a controlled manner using a trigger system based on hydrolysis catalyzed by endogenous ß-glucosidase. This led to glucose release from the hyaluronic acid backbone inside the cell. Indeed, our hydrogel proved to rescue starvation and cell mortality in a glucose-free medium. Our approach of adding a nutrient to the polymer backbone in hydrogels opens new avenues to deliver stem cells in poorly vascularized, nutrient-deficient environments, such as osteoarthritic joints, and for other regenerative therapies.

Keywords
  • Mesenchymal stem cell
  • Osteoarthritis
  • Regenerative cell therapy
  • Hyaluronic acid
  • Glucose
Citation (ISO format)
GONZALEZ FERNANDEZ, Paula et al. Hyaluronan-based hydrogel delivering glucose to mesenchymal stem cells intended to treat osteoarthritis. In: International journal of pharmaceutics, 2024, vol. 657, p. 124139. doi: 10.1016/j.ijpharm.2024.124139
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Journal ISSN0378-5173
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Technical informations

Creation14/05/2024 10:54:13
First validation14/10/2024 11:43:16
Update24/01/2025 15:10:36
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