Using Platelet-Rich Plasma Hydrogel to Deliver Mesenchymal Stem Cells into Three-Dimensional PLGA Scaffold for Cartilage Tissue Engineering

Abstract

The synthetic biodegradable polyester-based rigid porous scaffolds and cell-laden hydrogels have been separately employed as therapeutic modality for cartilage repair. However, the synthetic rigid scaffolds alone may be limited due to the inherent lack of bioactivity for cartilage regeneration, while the hydrogels have insufficient mechanical properties that are not ideal for load-bearing cartilage applications. In the present study, a hybrid construct was designed to merge the advantage of 3D-printed rigid poly­(lactic-co-glycolic acid) (PLGA) scaffolds with cell-laden platelet-rich plasma (PRP) hydrogels that can release growth factors to regulate the tissue healing process. PRP hydrogels potentially achieved the effective delivery of mesenchymal stem cells (MSCs) into PLGA scaffolds. This hybrid construct could obtain adequate mechanical properties and independently provide MSCs with appropriate clues for proliferation and differentiation. Real-time gene expression analysis showed that PRP stimulated both chondrogenic and osteogenic differentiation of MSC seeding into PLGA scaffolds. Finally, the hybrid constructs were implanted into rabbits to simultaneously regenerate both articular cartilage and subchondral bone within osteochondral defects. Our findings suggest that this unique hybrid system could be practically applied for osteochondral regeneration due to its capacity for cell transportation, growth factors release, and excellent mechanical strength, which would greatly contribute to the progress of cartilage tissue engineering.

Special Features of Polyester-Based Materials for Medical Applications

“…The usual techniques for preparing modified polyesters for artificial bone-substitute materials involve 3D printing [ 51 , 61 , 65 , 66 , 72 , 74 , 75 , 76 ], thermally induced phase separation (TIPS) [ 32 ], salt leaching [ 32 , 69 , 79 ], solvent casting [ 33 , 35 , 77 , 79 ], electrospinning [ 60 , 64 , 70 ], copolymerization [ 31 ], and polycondensation [ 73 ].…”

Progress of Platelet Derivatives for Cartilage Tissue Engineering

“…The clotting ability of activated platelet derivatives expands their application so that they can be applied to the surface of CTE constructures as a coating ( Luo et al, 2020 ), or gel with a 3D printed frame emerging-in as shown in Figure 5A ( Tang Y. et al, 2021 ). In such cases, the platelet derivatives are attached to molded biomaterials, therefore the influences on mechanical and degradation properties are minor.…”

“…(A) 3D printed PLGA frames are immersed in MSC-suspended PRP solution, and then the gelation of PRP is induced by addition of CaCl 2 solution with thrombin to complete the CTE construct. Reproduced with permission from Tang Y. et al (2021) . (B) Biomaterials, MSCs, and PRP are all mixed together before fabrication process to construct the synergistic scaffold.…”

“…Tang et al 3D printed the frame with poly (lactide-co-glycolide) (PLGA) and laden BMSCs and PRP onto the scaffold in one step though induced gelation. The scaffold had been completely absorbed 8 weeks after the implantation ( Tang Y. et al, 2021 ). Zhang et al manufactured bilayer PLGA scaffolds with different pore sizes by compression molding and particulate leaching.…”

Advances in the Treatment of Partial-Thickness Cartilage Defect

“…43 The lack of standards for PRP in terms of factors such as centrifugation speed and time leads to a wide variation in platelet and leukocyte concentrations, which affects the therapeutic effect. 44 In sum, more and more studies have shown that PRP can improve clinical cartilage pathology, and some scholars have applied PRP to cartilage tissue engineering, [45][46][47][48] but how and why it plays a role in cartilage repair is unclear, 49 which can be used as the next research direction. likely to induce hyaline cartilage production than BMP7, IGF1 or IGF2.…”