Fixation of Hydrogel Constructs for Cartilage Repair in the Equine Model: A Challenging Issue

• Published in: Tissue engineering. Part C, Methods Methods, 2017-11, Vol.23 (11), p.84-814
• Main Authors: Mancini, Irina A.D., Vindas Bolaños, Rafael A., Brommer, Harold, Castilho, Miguel, Ribeiro, Alexandro, van Loon, Johannes P.A.M., Mensinga, Anneloes, van Rijen, Mattie H.P., Malda, Jos, van Weeren, René
• Format: Article
• Language: English
• Subjects: Anchors; Animals; Arthritis; Bone growth; Bone Regeneration - drug effects; Bone resorption; Bovidae; Cartilage; Cartilage, Articular - diagnostic imaging; Cartilage, Articular - pathology; Computed tomography; Defects; Disease Models, Animal; Femur; Fibrin; Fibrin Tissue Adhesive - pharmacology; Histology; Horses; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogels; Implants, Experimental; Inflammation - pathology; Integration; Knee; Leukocytes (neutrophilic); Medical research; Organ Size; Osteogenesis; Polycaprolactone; Polyesters - chemistry; Printing, Three-Dimensional; Researchers; Special Focus Articles; Sports injuries; Studies; Subchondral bone; Surgery; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds - chemistry; Veterinary medicine; Wound Healing - drug effects; X-Ray Microtomography
• ISSN: 1937-3384; 1937-3392
• DOI: 10.1089/ten.tec.2017.0200

Objective: To report on the experiences with the use of commercial and autologous fibrin glue (AFG) and of an alternative method based on a 3D-printed polycaprolactone (PCL) anchor for the fixation of hydrogel-based scaffolds in an equine model for cartilage repair. Methods: In a first study, three different hydrogel-based materials were orthotopically implanted in nine horses for 1–4 weeks in 6 mm diameter full-thickness cartilage defects in the medial femoral trochlear ridge and fixated with commercially available fibrin glue (CFG). One defect was filled with CFG only as a control. In a second study, CFG and AFG were compared in an ectopic equine model. The third study compared the efficacy of AFG and a 3D-printed PCL-based osteal anchor for fixation of PCL-reinforced hydrogels in three horses for 2 weeks, with a 4-week follow-up to evaluate integration of bone with the PCL anchor. Short-term scaffold integration and cell infiltration were evaluated by microcomputed tomography and histology as outcome parameters. Results: The first study showed signs of subchondral bone resorption in all defects, including the controls filled with CFG only, with significant infiltration of neutrophils. Ectopically, CFG induced clear inflammation with strong neutrophil accumulation; AFG was less reactive, showing fibroblast infiltration only. In the third study the fixation potential for PCL-reinforced hydrogels of AFG was inferior to the PCL anchor. PCL reinforcement had disappeared from two defects and showed signs of dislodging in the remaining four. All six constructs fixated with the PCL anchor were still in place after 2 weeks. At 4 weeks, the PCL anchor showed good integration and signs of new bone formation. Conclusions: The use of AFG should be preferred to xenogeneic products in the horse, but AFG is subject to individual variations and laborious to make. The PCL anchor provides the best fixation; however, this technique involves the whole osteochondral unit, which entails a different conceptual approach to cartilage repair.