Nanohybrid biodegradable scaffolds for TGF-β3 release for the chondrogenic differentiation of human mesenchymal stem cells

An ideal scaffold for bone tissue engineering should have chondroinductive, biodegradable, and biocompatible properties, as well as the ability to absorb and slowly release the biological molecules. In order to develop such a system to support bone tissue regeneration, in the present study, we developed a three-dimensional poly(L-lactic-co-glycolic acid) (PLGA)/Polycaprolactone (PCL) nanohybrid scaffold embedded with PLGA macroparticles (MPs) conjugated with TGF-β3 for the growth and chondrogenic differentiation of human mesenchymal stem cells (hMSCs). First, a microfluidic device was used to fabricate porous PLGA MPs with the sizes ranging from 10 to 50 µm. Next, the PLGA MPs were loaded with TGF-β3, mixed with PCL solution, and then electrospun to obtain PLGA-TGF-β3 MPs/PCL nanohybrid scaffold. Our results demonstrated that PLGA MPs fabricated using a microfluidic-based approach exhibited enhanced conjugation of TGF-β3 with over 80% loading efficiency and sustained release of TGF-β3. Furthermore, the results of glycosaminoglycan (GAG) content measurement and Safranin O staining revealed that the PLGA-TGF-β3 MPs and PLGA-TGF-β3 MPs/PCL nanohybrid scaffold can promote the proliferation and chondrogenic differentiation of hMSCs in vitro. Therefore, the PLGA-TGF-β3 MPs/PCL nanohybrid scaffold could pave the way for cartilage regeneration and have wide applications in regenerative medicine.