Bone Marrow-Derived Cell Concentrates Have Limited Effects on Osteochondral Reconstructions in the Mini Pig

Abstract

This study investigates the effects of seeding a chondrogenic and osteogenic scaffold with a bone marrowderived cell concentrate (BMCC) and reports the histological and mechanical properties 3 months after implantation in the miniature pig. Twenty defects (7 · 10 mm) were created in the femoral condyles of 10 miniature pigs. The defects were left empty (E), filled with the grafted cylinder upside down (U) or with a combined scaffold (S) containing a spongious bone cylinder (Tutobone Ò ) covered with a collagen membrane (Chondrogide Ò ). In a fourth group, the same scaffolds were implanted but seeded with a stem cell concentrate (S + BMCC). The animals were stained with calcein green after 2 weeks and xylenol orange after 4 weeks. After 3 months, the animals were sacrificed, and a mechanical analysis (Young's modulus), macroscopic, and histologic (ICRS Score) examination of the specimens was conducted. Young's modulus in the periphery was significantly lower for group E (67.5 -15.3 kPa) compared with untreated controls (171.7 -21.6 kPa, p < 0.04). Bone defects were smaller in group S (10% -8%) compared with E (27% -7%; p < 0.05). There was a trend toward smaller bony defects on comparing groups E and S + BMCC (11% -8%; p = 0.07). More red fluorescence was detected in group S + BMCC (2.3% -1.1%) compared with groups E (0.4% -0.2%) and U (0.5% -0.2%, p < 0.03). ICRS scores were higher for groups S (25.3 -3.8) and S + BMCC (26.2 -5.2, p < 0.01). In this animal model of osteochondral defects, stem cell concentrates enhance new bone apposition but fail to improve mechanical properties or histological appearance of cartilage regenerates in critical-sized defects.

Near-Infrared Spectroscopy Correlates with Established Histological Scores in a Miniature Pig Model of Cartilage Regeneration

“…Further histological evaluations are part of another publication [18]. We previously demonstrated in this animal model that stem cell concentrates enhance new bone formation but fail to improve mechanical properties or histological appearance of regenerated cartilage in critical size defects.…”

“…The NIRS data analysis was a part of an animal project that investigated the effects of seeding a chondrogenic and osteogenic scaffold with a bone-marrow-derived cell concentrate and reports the histological and mechanical properties 3 months after implantation in a miniature pig [18]. We created 20 osteochondral defects, 7 mm in diameter and 10 mm in height, in the femoral condyles of 10 miniature pigs.…”

“…20 ml of bone marrow aspirate were used to create 3 ml of concentrate. The concentrate was transferred in a custom made cell seeding device (manufactured by the Institutional Central Research Laboratories of Hannover Medical School (MHH) as previously described [18]. In one group the combined scaffold (S) containing a spongy bone cylinder (Tutobone ® ) covered with a collagen membrane (Chondrogide ® ) was seeded with the stem cell concentrate (S+BMCC).…”

“…The group size was n=5. The animals were euthanized after 3 months, and mechanical, macroscopic [18], histologic, and spectrometric analyses were performed. This publication reports the correlation of histologic and spectrometric results.…”

Healing of massive segmental femoral bone defects in minipigs by allogenic ASCs engineered with FLPo/Frt-based baculovirus vectors

“…Besides the aforementioned animals, minipig is a recommended large animal model for pre-clinical evaluation of human orthopedic implants [35], and has been employed to assess bone repair at different sites including tibia [36], calvaria [37], mandible [38] and cartilage [39,40]. Yet these studies focused on the evaluation of cells, scaffold materials and growth factors, alone or in combination.…”