PCL-MECM-Based Hydrogel Hybrid Scaffolds and Meniscal Fibrochondrocytes Promote Whole Meniscus Regeneration in a Rabbit Meniscectomy Model

Abstract

Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.

3D Printed Poly(ε-Caprolactone)/Meniscus Extracellular Matrix Composite Scaffold Functionalized With Kartogenin-Releasing PLGA Microspheres for Meniscus Tissue Engineering

“…The tensile modulus was 20.20 ± 1.54 MPa for the PCL scaffold and 27.15 ± 1.30 MPa and 27.46 ± 2.33 MPa for the PCL/MECM and PCL/MECM/-KGN µS scaffolds, respectively (Supplementary Figure 3). As reported by Chen et al (2019) the compression and tensile moduli of the native rabbit meniscus is 3.76 ± 0.14 MPa and 45.58 ± 1.30 MPa, respectively. Although the mechanical strength of these scaffolds was inferior to the native meniscus in terms of tensile modulus, the hybrid scaffold is desirably strong enough to withstand biomechanical forces and maintain structural integrity (Makris et al, 2011).…”

“…Thus, the construction of hybrid scaffolds with fiber-reinforced structure and biomimetic ECM is of great significance in the treatment of meniscus injuries. Our team has previously demonstrated the regenerative potential of the 3D printing PCL scaffolds infused with meniscus extracellular matrix (MECM) and alginate, from which the meniscal fibrochondrocyte-loaded hybrid scaffold presented promising meniscus regeneration in the rabbit meniscectomy model (Chen et al, 2019). Given that the PCL scaffolds are not adequate to recreate an instructive microenvironment for cell growth and tissue regeneration, incorporating MECM as a bioactive material into the PCL scaffold not only can achieve a macro-/microporous hierarchical structure but also conducive to cell migration and infiltration, and may subsequently be capable enough to promote the neo-meniscal tissue formation.…”

Advances and trends of hydrogel therapy platform in localized tumor treatment: A review

“…Presently, optimizing the performance of hydrogels seems to be an inevitable tendency and requires the joint efforts of researchers. In addition, synthesized materials are also diverse, including alcohols, acrylics, and their derivatives such as poly vinyl alcohol (PVA), 58 poly caprolactone (PCL), 59 polyethylene glycol (PEG), 60 poly lactic acid (PLA), 61 poly glycolic acid (PGA), 62 and poly lactic‐co‐glycolic acid (PLGA) 63 . Interestingly, these polymers are often combined with one another or with other substances to form a composite hydrogel for desirable properties.…”

Potential Applications of Advanced Nano/Hydrogels in Biomedicine: Static, Dynamic, Multi‐Stage, and Bioinspired

“…Six months later, the gross appearance and cartilage production were improved, suggesting that this system could perform whole meniscus regeneration. [148] Mesenchymal stem/stromal cells (MSCs) have also been delivered by hydrogels. The effect of hydrogels on the MSC transcriptome has been broadly characterized.…”

“…Six months later, the gross appearance and cartilage production were improved, suggesting that this system could perform whole meniscus regeneration. [ 148 ]…”