Biomedical Journal (Dec 2012)
Bioengineered periosteal progenitor cell sheets to enhance tendon-bone healing in a bone tunnel
Abstract
Background: Tendon-bone tunnel healing is crucial for long term success in anterior cruciate ligament (ACL) reconstruction. The periosteum contains osteochondral progenitor cells that can differentiate into osteoblasts and chondroblasts during tendon-bone healing. We developed a scaffold-free method using polymerized fibrin-coated dishes to make functional periosteal progenitor cell (PPC) sheets. Bioengineered PPC sheets for enhancing tendon-bone healing were evaluated in an extra-articular bone tunnel model in rabbit. Methods: PPC derived from rabbit tibia periosteum, cultivated on polymerized fibrin-coated dishes and harvested as PPC sheet. A confocal microscopy assay was used to evaluate the morphology of PPC sheets. PPC sheets as a periosteum to wrap around hamstring tendon grafts were pulled into a 3-mm diameter bone tunnel of tibia, and compared with a tendon graft without PPC sheets treatment. Rabbits were sacrificed at 4 and 8 weeks postoperatively for biochemical assay and histological assay to demonstrate the enhancement of PPC sheets in tendon-bone healing. Results: PPC spread deposit on fibrin on the dish surface with continuous monolayer PPC was observed. Histological staining revealed that PPC sheets enhance collagen and glycosaminoglycans deposition with fibrocartilage formation in the tendon-bone junction at 4 weeks. Collagen fiber with fibrocartilage formation at tendon-bone junction was also found at 8 weeks. Matured fibrocartilage and dense collagen fiber were formed at the tendon-bone interface at 8 weeks by Masson trichrome and Safranin-O staining Conclusions: Periosteal progenitor cell monolayer maintains the differentiated capacity and osteochondral potential in order to promote fibrocartilage formation in tendon-bone junction. Bioengineered PPC sheets can offer a new feasible therapeutic strategy of a novel approach to enhance tendon-bone junction healing.
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