The role of erythropoietin and bone marrow concentrate in the treatment of osteochondral defects in mini-pigs.

All available treatment options for osteochondral and chondral defects do not restore hyaline cartilage and are limited to decreasing associated pain, and maintaining or improving joint function. The purpose of this study was to evaluate the potential of erythropoietin (EPO) in combination with bone marrow aspiration concentrate (BMAC) in the treatment of osteochondral defects of mini-pigs.14 Goettinger mini-pigs, in which a 6 × 10 mm osteochondral defect in the medial femoral condyle of both knee joints was created, were randomized into four groups: biphasic scaffold alone, scaffold with EPO, scaffold with BMAC and scaffold in combination with EPO and BMAC. After 26 weeks all animals were euthanized and histological slides were evaluated using a modified ÓDriscoll Score.In the therapy groups, areas of chondrogenic tissue that contained collagen II were present. Adding EPO (p = 0.245) or BMAC (p = 0.099) alone to the scaffold led to a non-significant increase in the score compared to the control group. However, the combination of EPO and BMAC in the implanted scaffold showed a significant improvement (p = 0.02) in the histological score.The results of our study show that in mini-pigs, the combination of EPO and BMAC leads to an enhanced osteochondral healing. However, additional research is necessary to further improve the repair tissue and to define the role of MSCs and EPO in cartilage repair

The defects in all animals were randomized using a sealed envelope system to the following four treatment groups: scaffold alone (control group), scaffold combined with bone marrow aspiration concentrate (BMAC), scaffold combined with erythropoietin (EPO) and scaffold combined with EPO and BMAC (EPO+BMAC).

<p>The defects in all animals were randomized using a sealed envelope system to the following four treatment groups: scaffold alone (control group), scaffold combined with bone marrow aspiration concentrate (BMAC), scaffold combined with erythropoietin (EPO) and scaffold combined with EPO and BMAC (EPO+BMAC).</p

Modified ÓDriscoll score.

<p>Modified ÓDriscoll score.</p

Representative histological slides.

<p>Representative histological slides of the medial femoral condyle (toluidine-blue staining) of each group, a) control group b) BMAC c) EPO d) EPO+BMAC. Histologically, residual biomaterials of the biphasic scaffolds were consistently present in the osseous phase of every defect after 26 weeks. In the treatment groups the repair tissue in the cartilage phase stained positive for GAGs.</p

Osteochondral defect.

<p>In all 14 mini-pigs, a 6×10 mm cylindrical osteochondral defect in the medial femoral condyle of both knee joints was surgically created with a cylindrical chisel (a). The defect site was exposed and then rinsed with a sterile saline solution (b). An osteochondral cylinder was created with a chisel in comparison to a TRUFIT plug (c). When implanted into the medial femoral condyle it was ensured that the plug was not protruding the surface of the adjacent cartilage (d).</p

Immunohistochemical analysis for collagen II.

<p>Immunohistochemical analysis for collagen II of the regenerate cartilage in representative slides of all four groups. a) control group b) BMAC c) EPO d) EPO+BMAC. In the defects of the therapy groups, areas of chondrogenic tissue, which contained collagen II on the basis of positive immunostaining, were present. However, in the control group the regenerative tissue was generally fibrous. This tissue was deficient in collagen type II as shown by specific staining.</p

Cone-beam computed tomography.

<p>Cone-beam computed tomography of a representative medial femoral condyle delineated a cystic radiolucent area, which was smaller than the originally cylindrical repair area, indicating that the bone adjacent to the implanted scaffold began to remodel starting from the edges of the defect.</p