The 3D-Printed PLGA Scaffolds Loaded with Bone Marrow-Derived Mesenchymal Stem Cells Augment the Healing of Rotator Cuff Repair in the Rabbits

Abstract

The healing of tendon–bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs–PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs–PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs–PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon–bone interface. The biomechanical analysis showed that BMSCs–PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon–bone healing in the rabbit rotator cuff repair model.

Biomimetic gradient scaffolds for the tissue engineering and regeneration of rotator cuff enthesis

“…Recently, stem cell transplantation has emerged as a promising approach and plays a pivotal role in tissue engineering owing to their inherent capacity for self-renewal and differentiation into targeted lineages at the repair site [189]. In terms of employing either a single cell type or a combination of various MSCs, there have been reports showing the separate use of BMSCs [190], ADSCs [191], or tendonderived stem cells (TDSCs) [192] to promote enthesis regeneration. In addition, a combined application of BMSCs and neural stem cells has been reported for the treatment of spinal cord injury in rats [193].…”

Strategies for promoting tendon-bone healing: Current status and prospects

“…It was found that this treatment strategy significantly improved cartilage degeneration and reduced the severity of joint fibrosis. Similarly, (Chen et al, 2020) developed polylactic acid-glycolic acid (PLGA) scaffolds loaded with BMSCs. In a rabbit RCT repair model, it was found to promote tendon-bone healing by improving the biomechanical properties of the regenerated tendon.…”

Advances in Stem Cell Therapies for Rotator Cuff Injuries

“… Kida et al (2013) found that drilled holes in the humerus footprint could stimulate autologous BMSCs to infiltrate into the repair site to promote tendon–bone healing by enhancing the ultimate force-to-failure. Exogenous BMSC can be delivered to the repair site by various carriers ( Chen P. et al, 2020 ). The untreated BMSCs increased the early formation of fibrocartilage and collagen orientation as well as biomechanical strength at 2 weeks.…”

“…The rate of degradation determines its usage. For example, polymers with a low degradation rate, such as PCL, are suitable for building longer-term tendon scaffolds ( Laranjeira et al, 2017 ; Calejo et al, 2019 ), while polymers with faster degradation rates are less suitable since they may increase the inflammation response, including PLA, PGA, and PLGA ( Yokoya et al, 2008 ; Vuornos et al, 2016 ; Chen et al, 2019 ; Chen P. et al, 2020 ; Araque-Monrós et al, 2020 ; El Khatib et al, 2020 ). According to this characteristic, a PEG-based hydrogel system with a range of degradation rates can control the timing of MSC delivery to the target site of tendinopathy ( Qiu et al, 2011 ).…”