Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

Abstract

BackgroundInsulin-like growth factor-I (IGF-I) plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH), or both (GH+IGF-I) would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs), while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments.ResultsTissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to) values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF-I.ConclusionThese results support two of our hypotheses that systemic administration of IGF-I or GH+IGF-I improve healing in collagenous tissue. Systemic administration of IGF-I improves healing in collagenous extracellular matrices from loaded and unloaded tissues. Growth hormone alone did not result in any significant improvement contrary to our hypothesis, while GH + IGF-I produced remarkable improvement in hindlimb unloaded animals.

Instrument-Assisted Cross-Fiber Massage Accelerates Knee Ligament Healing

“…21 The alignment and organization of newly formed collagen fibers in the direction of tensile loads during healing influences ligament mechanical properties. 19,20 The qualitatively improved collagen fiber organization observed within the scar region of IACFM-treated ligaments in the current study is a possible explanation for why IACFM-treated ligaments had enhanced tensile mechanical properties. This will be the focus of future quantitative studies into IACFM effects on ligament morphology.…”

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

“…The primarily growth factors include angiogenic factors such as platelet-derived growth factor, 36 insulin-like growth factor-1, 37 and VEGF. [38][39][40] In the present study, the increased expression of VEGF in the MDSC-VEGF group could explain the higher capillary density observed in this group when compared to the PBS and the MDSCsFLT1 groups.…”

GH receptor blocker administration and muscle–tendon collagen synthesis in humans

“…However, the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis has been suggested to play a central role in stimulating collagen synthesis in connective tissue. More specifically, IGF-I stimulates collagen synthesis in fibroblasts in vitro [6], and in animal studies both local injections and systemic administration of IGF-I can improve healing of tendon and muscle after surgical trauma [7][8][9]. In healthy men, it has been shown that recombinant human GH (rhGH) supplementation over 2 weeks increases circulating IGF-I levels, tissue IGF-I mRNA expression and collagen protein synthesis in skeletal muscle and tendon [10].…”