Abstract
Summary Statement
A resorbable and biocompatible polymer-based scaffold was used for the proliferation and delivery of adipose derived stromal cells, as well as delivery of a cell growth/differentiation promoting factor for improved tendon defect regeneration.
Introduction
Surgeons perform thousands of direct tendon repairs annually. Repaired tendons fail to return to normal function following injury, and thus require continued efforts to improve patient outcomes. The ability to produce regenerate tendon tissue with properties equal to pre-injured tendon could lead to improved treatment outcomes. The aim of this study was to investigate in vivo tendon regeneration using a biodegradable polymer for the delivery of adipose derived stromal cells (ADSCs) and a polypeptide, growth/differentiation factor-5/(GDF-5), in a tendon gap model.
Patients & Methods
Female Fischer 344 rats underwent unilateral Achilles tenotomies. Defects were left un-repaired (Group 1-control), bridged using electrospun 65:35 polylactide-co-glycolide (PLAGA) tubular scaffolds (Group 2), PLAGA/ADSCs (Group 3), or PLAGA/GDF-5 (Group 4) scaffold composites. The plantaris was left intact. Operative limbs were immobilised for 10–14 days, followed by unrestricted activity. The rats were sacrificed at 4 weeks or 8 weeks after surgery, and tendons were assessed with histological, biochemical, and mechanical analyses.
Results
PLAGA, PLAGA/ADSCs, and PLAGA/GDF-5 groups showed increased collagen I gene expression at both the 4 and 8 week time points (p<0.05). Tenomodulin (Tnmd) is the mature tendon phenotype marker unique to tendon tissue. Both the PLAGA/ADSCs and PLAGA/GDF-5 groups demonstrated increased tenomodulin expression at 4 and 8 weeks (p<0.05). Ultimate tensile load strength was improved in all PLAGA groups (2, 3, and 4) versus the control. Both composite groups (2 and 3) showed improved collagen deposition, as indicated by increased Collagen Area Fraction (CAF), approaching that of normal tendon at 8 weeks (p<0.05). Scaffold resorption was evident at 4 weeks, with complete replacement of the polymer with regenerate tissue and minimal gap formation at 8 weeks without evidence of an adverse inflammatory reaction. Defects bridged using the scaffold seeded with ADSCs showed improved collagen organization and increased modulus of elasticity compared with controls as well as properties approaching those of native tendon.
Discussion/Conclusions
These results demonstrate that a tubular bioresorbable scaffold can promote extracellular matrix synthesis and organization, and the formation of neo-tendinous tissue; as well as serve as a carrier of adipose stromal cells and growth factors that are effective for tendon regeneration. Cells, growth factors and synthetic biomaterial polymers may be combined as a paradigm for regenerative engineering thereby serving as promising options for improved treatments of tendon injuries and potentially improving patient outcomes.
