Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

Abstract

Background The poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue. Results Herein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility. Conclusions Overall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration. Graphical Abstract

Bibliometric and visualization analysis of stem cell therapy for meniscal regeneration from 2012 to 2022

“…It is generally agreed that the repaired meniscus can function well based on the assumption that the meniscus has a correct shape and good topography that allows a stable load force transfer between the tibia and femur in the joint ( Hao et al, 2021 ). Moreover, whether on the size or the angle, there always exists a slight difference in the patients’ menisci ( Deng et al, 2021 ). Faced with this problem, 3D bioprinting can be used to manufacture artificial menisci containing MSCs with any shape and angle, which will certainly facilitate the individualized treatment of patients ( Filardo et al, 2019 ).…”

BMP-2-immobilized PCL 3D printing scaffold with a leaf-stacked structure as a physically and biologically activated bone graft

“…It is well known that the surface of biomaterials, which affects cell adhesion, proliferation, and differentiation, plays a crucial role in successful engraftment of biomaterials under the physiological environment for induction of target tissue regeneration [52][53][54][55]. To determine whether the LSS on the 3D-PLSS is a microtopographical cue for cell adhesion, the cell number and the expression of the focal adhesion markers of hPDCs incubated on LSS surfaces (3D-PLSS and 3D-PLSS-BMP groups) and smooth surfaces (3D-PS and 3D-PS-BMP groups) were compared.…”

Recent Advances in Decellularized Matrix-Derived Materials for Bioink and 3D Bioprinting

“…Cartilage is a connective tissue with supporting functions and has strong toughness [ 137 ]. Simulation of cartilage surface morphology is a feasible strategy for modeling cartilage composition and mechanical strength ( Figure 3 B) [ 138 , 139 ]. Many studies have been conducted on bioink with additional dECMs for 3D bioprinting cartilage.…”