Sustained Delivery of Chondrogenic Molecules Using Sugar Glass Nanoparticle-Integrated Fibrous Scaffolds for Cartilage Tissue Engineering

TL;DR

Researchers developed a new type of scaffold that slowly releases a growth factor to help bone marrow stem cells turn into cartilage cells, offering a promising approach for cartilage tissue engineering.

Contribution

The novel use of sugar glass nanoparticles to encapsulate and sustainably release TGFB1 in fibrous scaffolds for chondrogenic differentiation of BMSCs.

Findings

TGFB1 was sustained over 39 days from scaffolds incorporating sugar glass nanoparticles.

PLA-based scaffolds showed the highest cumulative TGFB1 release.

BMSCs on these scaffolds showed enhanced chondrogenic differentiation with upregulated cartilage markers.

Abstract

Biomaterial scaffolds capable of controlled release of bioactive molecules hold significant potential in tissue engineering, offering a promising avenue to enhance tissue regeneration. They provide localized and sustained delivery of biological cues to direct stem cell differentiation while creating a three-dimensional microenvironment that supports cell adhesion and growth.

In this study, we utilized reverse micelle sugar glass nanoparticles (SGnPs), previously developed by our team, to encapsulate the chondrogenic growth factor TGFB1. This approach aimed to preserve the bioactivity of these molecules before their release. The TGFB1-SGnPs were directly incorporated into electrospun fibrous scaffolds, engineered specifically to ensure the sustained release of the growth factor during the culture of human bone marrow-derived mesenchymal stem/stromal cells (BMSCs).

TGFB1 was released in a sustained manner over 39 days from TGFB1-SGnP-incorporated fibrous scaffolds, made from poly (ε-caprolactone), poly (d-lactic acid) (PLA), and poly (lactic-co-glycolic acid). Among these formulations, the PLA-based scaffolds demonstrated the highest cumulative TGFB1 release over the study period. In vitro cell studies demonstrated that TGFB1-SGnP-PLA fibrous scaffolds supported the proliferation of BMSCs and enhanced chondrogenic differentiation. Transcript expression analysis of BMSCs seeded on TGFB1-SGnP-PLA fibrous scaffolds induced for chondrogenesis revealed an upregulation of chondrocyte-associated markers, including SOX9, ACAN, COL2A1, and COL1A1.

This study demonstrates the potential of using SGnPs to protect and deliver chondrogenic induction molecules from electrospun fibrous scaffolds in a sustained manner, promoting the chondrogenic differentiation of BMSCs in cartilage tissue engineering.

Lay Summary.

Researchers have developed advanced biomaterial scaffolds that release bioactive molecules to enhance tissue regeneration. These “smart scaffolds” provide a three-dimensional environment for cell growth and localized cues to support biological functions. Utilizing sugar glass nanoparticles (SGnPs) to encapsulate growth factors like TGFB1, electrospun fibrous scaffolds incorporating TGFB1-SGnPs were crafted to assess their effectiveness in supporting the activity of human bone marrow-derived mesenchymal stem/stromal cells (BMSCs). Results showed that TGFB1, particularly from TGFB1-SGnP-PLA scaffolds, significantly promoted BMSC proliferation and chondrogenic differentiation, as evidenced by increased markers associated with cartilage cells. This innovative approach demonstrates considerable potential for advancing cartilage tissue engineering and offers a new therapeutic strategy for conditions such as osteoarthritis, enhancing tissue repair and regeneration.

Figures