The objective of this study was to test the governing hypothesis that implanting mesenchymal stem cell (MSC)-seeded collagen gel and polyglyconate suture scaffolds into surgically induced rabbit patellar tendon defects will increase the repair tissues' structural and material properties in proportion with the implant cell-seeding density compared to untreated defects.
Increasing the seeding density of the implants beyond 1 million cells/ml accelerated contraction of the implants in vitro in the first 24 hours. The 4 and 8 million cells/ml implants contracted to less than 25% of their initial diameters by 72 hours. Concomitant with these physical changes in implant dimensions, the nuclear morphology of the seeded MSCs was also affected by the initial seeding density. Nuclei were significantly better aligned and had lower aspect ratios at 72 hours, especially in the most densely seeded constructs. However, the cell density-dependent effects on the contraction kinetics of the implants in vitro did not translate into significant effects on the repair biomechanics in vivo due to the large biological variability that may have masked the seeding density effects.
Results also demonstrated that implanting oriented MSC-seeded collagen scaffolds of various seeding densities into full-length central third PT defects improved repair biomechanics compared to untreated repair at 12 and 26 weeks. The structural properties of the MSC-seeded tissues reached values over 150% of untreated repair values at 12 weeks, and almost tripled untreated repair values at 26 weeks. The maximum stress and modulus were also 37% to 94% and 43% to 50% greater for the MSC-seeded repair tissues than for natural repair values at 12 and 26 weeks, respectively. However, mesenchymal stem cell-seeded repair tissues remain significantly weaker and more compliant than normal tissues, reaching values of just one-fourth of the maximum stress and modulus of normal patellar tendon at 26 weeks. In addition, a subset of the MSC treated tissues formed ectopic bone at the repair site.
These results, while demonstrating the potential benefits of implanting MSC seeded collagen scaffolds in treating tendon injuries, suggest that more work must still be completed to optimize the MSC implant configuration and to improve the repair outcome in vivo.