Local Application of Gelatin Hydrogel Sheets Impregnated With Platelet-Derived Growth Factor BB Promotes Tendon-to-Bone Healing After Rotator Cuff Repair in Rats.
OBJECTIVE
To determine whether the local application of platelet-derived growth factor BB (PDGF-BB) in hydrogel sheets would promote healing and improve histologic characteristics and biomechanical strength after rotator cuff (RC) repair in rats.


METHODS
To assess the effect of PDGF-BB on tendon-to-bone healing we divided 36 adult male Sprague-Dawley rats treated with bilateral surgery to repair the supraspinatus tendon at its insertion site into 3 groups: group 1 = suture-only group; group 2 = suture and gelatin hydrogel sheets impregnated with phosphate-buffered saline (PBS); and group 3 = suture and gelatin hydrogel sheets impregnated with PDGF-BB (0.5 μg). Semiquantitative histologic evaluation was carried out 2, 6, and 12 weeks later; cell proliferation was assessed 2 and 6 weeks postoperatively by immunostaining for proliferating cell nuclear antigen (PCNA), and biomechanical testing, including ultimate load to failure, stiffness, and ultimate stress to failure, was performed 12 weeks after the operation.


RESULTS
At 2 weeks, the average percentage of PCNA-positive cells at the insertion site was significantly higher in group 3 (40.5% ± 2.4%) than in group 1 (32.1% ± 6.9%; P = .03) and group 2 (31.9% ± 3.7%; P = .02). At 2 and 6 weeks, the histologic scores were similar among the 3 groups. At 12 weeks, the histologic score was significantly higher in group 3 (10.3 ± 0.8) than in group 1 (8.5 ± 0.5; P = .002) or group 2 (8.8 ± 0.8; P = .009), whereas ultimate load to failure, stiffness, and ultimate load to stress (normal control population, 44.73 ± 9.75 N, 27.59 ± 4.32 N/mm, and 21.33 ± 4.65 N/mm(2), respectively) were significantly higher in group 3 (28.28 ± 6.28 N, 11.05 ± 2.37 N/mm, and 7.99 ± 2.13 N/mm(2), respectively) than in group 1 (10.44 ± 1.98 N, 4.74 ± 1.31 N/mm, and 3.28 ± 1.27 N/mm(2), respectively; all P < .001) or group 2 (11.85 ± 2.89 N, 5.86 ± 1.75 N/mm, and 3.31 ± 0.80 N/mm(2), respectively; all P < .001).


CONCLUSIONS
The placement of a PDGF-BB-impregnated hydrogel sheet just lateral to a transected and acutely reattached supraspinatus tendon produced significantly more PCNA-positive cells at 2 weeks and greater collagen fiber orientation, ultimate failure loads, stiffness, and stress to failure at 12 weeks than did a PBS-impregnated hydrogel sheet. No differences in vascularity or cellularity were observed.


CONCLUSIONS
The local application of PDGF-BB-impregnated gelatin hydrogel may help to promote tendon-to-bone healing after RC repair in humans.
Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: ttokunaga@fc.kuh.kumamoto-u.ac.jp.
Takuya
T
Tokunaga
Department of Advanced Joint Reconstructive Surgery, Kumamoto University Hospital, Kumamoto University, Kumamoto, Japan.
Junji
J
Ide
Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Hitoshi
H
Arimura
Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Takayuki
T
Nakamura
Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Yusuke
Y
Uehara
Department of Mechanical System Engineering, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan.
Hidetoshi
H
Sakamoto
Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Hiroshi
H
Mizuta
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001178:Arthroplasty; D000077214:Becaplermin; D001696:Biomechanical Phenomena / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D005780:Gelatin / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D008297:Male; D019637:Orthopedic Procedures; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000187:drug effects* / Q000601:surgery; D013710:Tendons / Q000187:drug effects* / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects*
D043925:Angiogenesis Inducing Agents; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin