title: Calcium-phosphate matrix with or without TGF-β3 improves tendon-bone healing after rotator cuff repair.
abstract: BACKGROUND
  Rotator cuff tendon heals by formation of an interposed zone of fibrovascular scar tissue. Recent studies demonstrate that transforming growth factor-beta 3 (TGF-β(3)) is associated with tissue regeneration and "scarless" healing, in contrast to scar-mediated healing that occurs with TGF-β(1).
  
  
  OBJECTIVE
  Delivery of TGF-β(3) in an injectable calcium-phosphate matrix to the healing tendon-bone interface after rotator cuff repair will result in increased attachment strength secondary to improved bone formation and collagen organization and reduced scar formation of the healing enthesis.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Ninety-six male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon followed by acute repair using transosseous suture fixation. Animals were allocated into 1 of 3 groups: (1) repair alone (controls, n = 32), (2) repair augmented by application of an osteoconductive calcium-phosphate (Ca-P) matrix only (n = 32), or (3) repair augmented with Ca-P matrix + TGF-β(3) (2.75 µg) at the tendon-bone interface (n = 32). Animals were euthanized at either 2 weeks or 4 weeks postoperatively. Biomechanical testing of the supraspinatus tendon-bone complex was performed at 2 and 4 weeks (n = 8 per group). Microcomputed tomography was utilized to quantitate bone microstructure at the repair site. The healing tendon-bone interface was evaluated with histomorphometry and immunohistochemical localization of collagen types I (COLI) and III (COLIII). Statistical analysis was performed using 2-way analysis of variance with significance set at P < .05.
  
  
  RESULTS
  There was significantly greater load to failure of the Ca-P matrix + TGF-β(3) group compared with matrix alone or untreated controls at 4 weeks postoperatively (P = .04). At 2 weeks, microcomputed tomography revealed a larger volume of newly formed bone present at the healing enthesis in both experimental groups compared with the control group. By 4 weeks, this newly formed, woven bone had matured into calcified, lamellar bone. Histomorphometric analysis demonstrated significantly greater fibrocartilage and increased collagen organization at the healing tendon-bone insertion site in both experimental groups compared with the control group at 2 weeks (P = .04). Over time, TGF-β(3) delivery led to greater COLI expression compared with COLIII at the healing enthesis, indicating a more favorable COLI to COLIII ratio with administration of TGF-β(3).
  
  
  CONCLUSIONS
  Augmentation with an osteoconductive Ca-P matrix at the tendon-bone repair site is associated with new bone formation, increased fibrocartilage, and improved collagen organization at the healing tendon-bone interface in the early postoperative period after rotator cuff repair. The addition of TGF-β(3) significantly improved strength of the repair at 4 weeks postoperatively and resulted in a more favorable COLI/COLIII ratio.
  
  
  CONCLUSIONS
  The delivery of TGF-β(3) with an injectable Ca-P matrix at the supraspinatus tendon footprint has promise to improve healing after soft tissue repair.
authors.affiliation: Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York 10021, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kovacevic
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Fox
authors.forename: Asheesh
authors.initials: A
authors.lastname: Bedi
authors.forename: Liang
authors.initials: L
authors.lastname: Ying
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Deng
authors.forename: Russell F
authors.initials: RF
authors.lastname: Warren
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D002921:Cicatrix / Q000517:prevention & control; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000502:physiology / Q000601:surgery; D000070636:Rotator Cuff Injuries; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D002130:Calcium Phosphates; D053782:Transforming Growth Factor beta3; D003094:Collagen; C020243:calcium phosphate