Insulin-Like Growth Factor I Accelerates Functional Recovery from Achilles Tendon Injury in a Rat Model

Abstract

We studied the effects of insulin-like growth factor I on Achilles tendon healing in a rat model. Rats were randomized into groups of six each: sham surgery, transection alone, and transection plus growth factor. Postoperatively, rats treated with growth factor had a significantly smaller maximum functional deficit and a decreased time to functional recovery than rats in the untreated groups. Biomechanical testing revealed no significant differences in the measured parameters between the treated and the untreated groups after transection. To study the mechanism of action, six additional animals received an Achilles tendon injection of the inflammatory agent carrageenan alone and six received carrageenan plus growth factor. Rats treated with growth factor did not show the inflammation-induced functional deficit experienced by the control rats. Spectrometric myeloperoxidase assays on the remaining eight rats after Achilles tendon transection demonstrated no significant difference between the untreated and the growth factor-treated groups, indicating a mechanism other than neutrophil recruitment by which the growth factor limits inflammation. Histologic studies were performed on carrageenan-injected rats at postinjection day 2 and on surgically treated rats at postoperative day 15. No gross histologic differences were seen between untreated and growth factortreated groups. This study demonstrated that via a possible antiinflammatory mechanism, insulin-like growth factor I reduces maximum functional deficit and accelerates recovery after Achilles tendon injury.

Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat

“…Under the most severe conditions of transected ligament, with BPC 157 mg-ng-regimens given alone intraperitoneally, per-orally and topically, dose-regimens and application methods that had been successfully used before [1][2][3][4][5][6][7][8][9][10][11][12] and in time, the healing process on an acute ligament injury may convert rapidly from a failure to a success and all healing improvements. Function in either condition, normal (walking rats) and stressed (running rats), biomechanic, macro/microscopy were noted superior as before [1][2][3][4][5][6][7][8][9][10][11][12] in tendon studies 1,2,10 and other wound studies, 4,9,10,12 , not species related.…”

“…We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier, using stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV) (for review, see Refs. [1][2][3][4][5][6][7][8][9][10][11][12] ). Previously, as an anti-ulcer peptide stable in human gastric juice [4][5][6][7][8][9] BPC 157 was effective in inflammatory bowel disease therapy (PL 14736) (no toxicology reported (for review, see Ref.…”

“…Also, BPC 157 particularly improved healing of transected tendon and muscle 1,2,10,11 and wound healing effect including the expression of the early growth response 1 (egr-1) gene (but also its repressor nerve growth factor 1-A binding protein-2 (nab2)). [4][5][6]9,10,12,13 Therefore, such peptide's capabilities [1][2][3][4][5][6][7][8][9][10][11][12] and responsibility for cytokine and growth factor generation and early extracellular matrix (collagen) formation may provide a peptide therapy effective functionally, biomechanically, macroscopically, and microscopically, [1][2][3][4][5][6]9,10,12,13 and thereby, suitable to improve ligament healing.…”

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157

“…1419, PL-10, PLD-116, PL 14736, Pliva, Croatia, in clinical trials for inflammatory bowel disease, 3 ulcer, and wound treatment, [1][2][3][4][5][6][7][8][9][10][11][12] no toxicity reported 3 ) could resolve unclear systemic peptide treatment of major muscle injury. Of note, like in tendon-healing, 13 muscle-healing with standard peptide (in)efficiency, 14 uncertain delivery, 15 besides carrier addition, 13,15 unable to deliver healing to an injured muscle, essentially restraints the systemic peptide treatment. Mostly limited to direct local administration, standard peptide growth factors 14 elicit no full muscle recovery, but rather scar tissue accumulation, 14 even confronted with less severe injuries [besides, wound healing by transforming growth factor (TGF)-b given with carrier 16 contrasts with muscle healing attempts with antifibrotic agents, TGF-b1 inhibitors 14 ].…”

Growth Hormone Does Not Stimulate Early Healing in Rat Tendons

“…This up-regulation was seen both during an early and a later phase of healing. Moreover, local IGF-1 treatment following Achilles tendon transection in rats resulted in faster functional recovery compared to controls 14 days after transection [18].…”