Mechanoactive scaffold induces tendon remodeling and expression of fibrocartilage markers.
Biological fixation of soft tissue-based grafts for anterior cruciate ligament (ACL) reconstruction poses a major clinical challenge. The ACL integrates with subchondral bone through a fibrocartilage enthesis, which serves to minimize stress concentrations and enables load transfer between two distinct tissue types. Functional integration thus requires the reestablishment of this fibrocartilage interface on reconstructed ACL grafts. We designed and characterized a novel mechanoactive scaffold based on a composite of poly-alpha-hydroxyester nanofibers and sintered microspheres; we then used the scaffold to test the hypothesis that scaffold-induced compression of tendon grafts would result in matrix remodeling and the expression of fibrocartilage interface-related markers. Histology coupled with confocal microscopy and biochemical assays were used to evaluate the effects of scaffold-induced compression on tendon matrix collagen distribution, cellularity, proteoglycan content, and gene expression over a 2-week period. Scaffold contraction resulted in over 15% compression of the patellar tendon graft and upregulated the expression of fibrocartilage-related markers such as Type II collagen, aggrecan, and transforming growth factor-beta3 (TGF-beta3). Additionally, proteoglycan content was higher in the compressed tendon group after 1 day. The data suggest the potential of a mechanoactive scaffold to promote the formation of an anatomic fibrocartilage enthesis on tendon-based ACL reconstruction grafts.
Department of Biomedical Engineering, Biomaterials and Interface Tissue Engineering Laboratory, Columbia University, 351 Engineering Terrace Building, MC 8904, 1210 Amsterdam Avenue, New York, NY 10027, USA.
Jeffrey P
JP
Spalazzi
Moira C
MC
Vyner
Matthew T
MT
Jacobs
Kristen L
KL
Moffat
Helen H
HH
Lu
D053674:Aggrecans / Q000378:metabolism; D016118:Anterior Cruciate Ligament / Q000601:surgery; D000070598:Anterior Cruciate Ligament Injuries; D024043:Collagen Type II / Q000378:metabolism; D019245:Compressive Strength; D051445:Fibrocartilage / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019344:Lactic Acid / Q000627:therapeutic use; D018613:Microscopy, Confocal; D036103:Nanotechnology; D011100:Polyglycolic Acid / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013314:Stress, Mechanical; D013710:Tendons / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D053782:Transforming Growth Factor beta3 / Q000378:metabolism
D053674:Aggrecans; D024043:Collagen Type II; D006025:Glycosaminoglycans; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid