Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

Abstract

Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques.

Hydrogel‐Guided, rAAV‐Mediated IGF‐I Overexpression Enables Long‐Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large‐Animal Full‐Thickness Chondral Defect Model at One Year In Vivo

“…After meticulously removing the articular cartilage within the defect with a curette including all calcified cartilage down to the subchondral bone plate that was left intact, three uniform microfracture holes were introduced (1.2 mm diameter, 5 mm depth) using a custom‐made microfracture awl with a straight trihedral cutting tip and a penetration stop. [ 57 ] The hydrogel systems (IGF‐I/AlgPH155 or lacZ /AlgPH155) (25 µL per defect; 3.6 × 10 5 transgene copies) [ 23 ] were implanted in the defects that were prior blotted dry using a spatula where they adhered to the subchondral bone plate treated with microfracture. Following implantation, the joint was taken through several ranges of motion to test the stability of the hydrogel.…”

Stellenwert des Débridements bei der Behandlung fokaler (Grad II – III) Knorpelschäden des Kniegelenks. Systematische Literaturübersicht und Empfehlungen der AG Geweberegeneration (DGOU)

“…Interessanterweise scheint durch ein derartiges (tiefes) Débridement der subchondrale Knochen in einem größeren Maß affektiert zu werden, als bisher angenommen. Im Minipigmodell (mit allerdings dünnerer subchondraler Platte als beim Menschen) fand sich 4 Wochen nach alleinigem Débridement eine deutliche Schwächung der subchondralen Knochenstruktur im Bereich unter dem vollschichtigen Knorpeldefekt mit signifikanter Osteoklastenaktivität [47].…”

Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns

“…Here, relevant TGF-b1 concentrations within the repair tissue of the TGF-b1 group were observed especially in the superficial and deep zones in vivo, without relevant immunoreactivity in controls. The slow-release profile corresponding to 10% of the total amount loaded was especially selected to minimize undesirable adverse effects when using high doses of this growth factor (23,24). At this early time point, no significant differences in the microstructural subchondral bone repair within the osteochondral defect occupied by the scaffolds were found.…”

“…We have previously demonstrated the suitability of porous scaffolds that are composed of poly(ethylene oxide)-terephtalate/poly(butylene terephthalate) (PEOT/ PBT) to allow for a controlled and sustained TGF-b1 release for at least 21 d in vitro (22). As much of our current understanding of chondrogenesis in cartilage defects is based on studies in small animals, such as mice or rabbits, we chose the large animal model of osteochondral defects in the distal medial femoral condyles in the stifle joints of adult minipigs (23). We hypothesized that the sustained presence of the TGF-b1 protein in such defects in situ results in an enhanced recruitment of progenitor cells into the defect site in vivo, which improves early chondrogenic repair.…”