The potential use of allogeneic platelet rich plasma for large bone defect treatment: Immunogenicity and defect healing efficacy

摘要

Platelet rich plasma (PRP) can be easily isolated from peripheral blood and used as an excellent nature biomaterial with the beneficial effect to promote bone defect healing. However, the clinical application of autologous PRP is harassed by controversial therapeutic outcome, due to highly variable PRP quality among patients. Alternatively, allogeneic PRP prepared from well-characterized donors may generate more consistent and reliable therapeutic effect. Moreover, using allogeneic PRP can avoid additional procedure to harvest large quantity of blood, eliminating extra health burdens on patients, especially in trauma conditions. However, the use of allogeneic PRP for bone defect treatment is generally less investigated, especially for its immunogenicity in such application. Here, we meticulously investigated the immunogenicity of allogeneic PRP in the absence of major histocompatibility complex (MHC) matching and evaluated its healing efficacy for critical sized defects treatment. The intramuscular injection of allogeneic PRP to rabbits did not trigger severe and chronic immuno-response, evidenced by little change in muscular tissue microstructure and CD4+ /CD8+ T lymphocyte subpopulation in peripheral blood. The implantation of allogeneic PRP mediated deproteinized bone matrix (DPB) constructs (PRP+DPB) successfully bridged 1.5 cm segmental radial defects in rabbits, achieving similar healing capacity as autologous MSC loaded DPB constructs (MSC+DPB), with greater bone formation (1.1-1.5x, p＜0.05) and vascularization (1.3-1.6x, p＜0.05) than DPB alone, shown by histomorphometric analysis, bone mineral density measurement and radionuclide bone imaging. Furthermore, the implantation of both allogeneic PRP and autologous MSC mediated DPB constructs (PRP+MSC+DPB) resulted in the most robust bone regeneration (1.2-2.1x, p＜0.05) and vascularization (1.3-2.0x, p＜0.05) than others (PRP+DPB, MSC+DPB or DPB alone).