Hydrophilic/Hydrophobic Janus Nanofibers Containing Compound K for Cartilage Regeneration

Abstract

Introduction

Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects.

Methods

Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1β (IL-1β) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated.

Results

CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1β was reduced through the upregulation of PPAR.

Conclusion

CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1β via increasing PPAR.

Graphical Abstract

Keywords:

• polycaprolactone nanofibers
• gallic acid-conjugated chitosan
• compound K
• hydrophilic coating
• adhesive material
• cartilage regeneration

Abbreviations

PCL, polycaprolactone; NFs, nanofibers; CHI-GA, gallic acid-conjugated chitosan; CK, compound K; DMM, destabilization of the medial meniscus; IL-1β, interleukin-1β; PPAR, peroxisome proliferator-activated receptor; OA, osteoarthritis; MMPs, matrix metalloproteinases; NMR, nuclear magnetic resonance; UV-Vis, ultraviolet-visible; SEM, scanning electron microscope, WCA, water contact angle; ADAMTS, A disintegrin and metalloproteinase with thrombospondin motifs; OARSI, Osteoarthritis Research Society International.

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (2022R1A4A1031259 and 2021R1I1A3041149) to E-JJ. and supported by the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (22A0103L1) to JHR.

Disclosure

Professor Ji Hyun Ryu reports a patent DRUG DELIVERY SYSTEM AND ITS MACUFACTURING METHOD pending to Wonkwang University (Yeo Jin Kim, Dong Hyeon Kim, June Young Park, Ji Hyun Ryu, Eun-Jung Jin). The authors report no other conflicts of interest in this work.