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

BACKGROUND: Insulin-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. RESULTS: Tissues 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. CONCLUSION: These 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

Transient and cyclic responses of strain-generated potential in rabbit patellar tendon are frequency and pH dependent

The goal of this study was to expand understanding of strain-generated potential (SGP) Suh (1996, Biorheology, 33, pp. 289-304) and Chen (1996, Ph.D. thesi

Ex vivo biomechanics of Kirschner-Ehmer external skeletal fixation applied to canine tibiae.

peer reviewedThe purpose of this study was to determine the respective contribution of each of the following parameters to the compressive, bending, and torsional rigidity of the Kirschner-Ehmer (KE) external fixation splint as applied to canine tibiae with an osteotomy gap: bilateral versus unilateral splints; increasing the number of fixation pins; altering the diameter of fixation pins and side bars; decreasing side bar distances from the bone; increasing pin separation distances in each pin group; decreasing distances between pin groups; altering pin clamp orientation; and altering side bar conformation. Bilateral splints were 100% (mean) stiffer than unilateral splints, with stiffness enhanced to the greatest extent in mediolateral bending and torsion. Increasing pin numbers stiffened both bilateral (mean, 41%; 8 versus 4) and unilateral splints (mean, 14%; 8 versus 4). Medium KE splints were 85% (mean) stiffer than small KE splints. Decreasing side bar distances to the bone from 1.5 cm to 1.0 cm to 0.5 cm increased stiffness of both bilateral and unilateral splints by a mean of 13% to 35%. Widening pin spacing from 1.67 cm to 2.5 cm increased stiffness in craniocaudal bending only (56% increase, bilateral splints; 73% increase, unilateral splints). Decreasing the distance between pin groups from 5.84 cm to 2.5 cm increased stiffness in torsion between 23% (unilateral splints) and 45% (bilateral splints) and decreased stiffness of unilateral splints by 29% in craniocaudal bending. Altering pin clamp configuration so that the bolts of the clamp were inside the side bar rather than outside the side bar increased stiffness in axial compression only (73% increase, bilateral splints; 54% increase, unilateral splints). Conforming the lateral side bar to the tibiae increased only axial compressive stiffness by 77% but was no different than placing the clamps inside the side bars of an unconformed bilateral splint. These results quantify the relative importance of specific parameters affecting KE splint rigidity as applied to unstable fractures in the dog

Comparison of healing of allograft/endoprosthetic composites with three types of gluteus medius attachment.

peer reviewedThis study compared three methods of gluteus medius tendon attachment to an allograft/endoprosthetic composite of the proximal 25% of the femur in a canine model. The three methods were bone to bone, tendon to bone, and tendon to tendon attachment. In an in vivo study, 24 dogs were assigned to three groups of eight dogs each, and serial radiography and weight-bearing analyses were performed throughout the study. The dogs were killed at 6 months, and the specimens were tested in tension to failure and were analyzed histologically. In an in vitro study, each repair was done on six limbs, with a contralateral limb serving as a control for each. In these specimens, the bone to bone attachments were significantly stronger (99.1% of the controls) than the tendon to bone attachments (71.8% of the controls) and the tendon to tendon attachments (40.0% of the controls); there were no differences in tensile stiffness among the three types of attachment. By 6 months, the tensile strength of the tendon to tendon attachments increased significantly and that of the tendon to bone attachments decreased significantly. There were no significant differences in tensile strength among the three types of attachment. The tensile stiffness of the bone to bone attachments (91.0% of the controls) was significantly greater than that of the tendon to bone attachments (40.8% of the controls) but not significantly different from that of the tendon to tendon attachments (63.2% of the controls). The bone to bone attachment was associated with increased bone resorption, bone remodeling, and bone porosity, accompanied by thinner allograft cortices, when compared with the other types of attachment. In dogs with a bone to bone attachment, weight-bearing increased more slowly than in dogs with either of the other two attachments. These changes associated with the bone to bone attachment may merely be secondary to healing of the bone to bone attachment to the greater trochanter; therefore, they may only be temporary phenomena or they may be the portents for long-term complications. Longer term studies of at least 1-2 years must be performed before these questions can be answered

Comparison of allograft/endoprosthetic composites with a step-cut or transverse osteotomy configuration.

peer reviewedThis study was designed to compare the biomechanical and functional characteristics of allograft/endoprosthetic composites of the proximal 25% of the femur repaired with either a transverse or a step-cut osteotomy, using a canine model (10 dogs, five with each type of osteotomy). Serial radiography and weight-bearing studies were performed monthly, and mechanical testing was done 6 months after surgery. The femora were tested in torsion and compared with the contralateral control (insertion of a femoral component but no osteotomy). At 6 months, the composites with a step-cut osteotomy had 36% greater structural stiffness than the composites with a transverse osteotomy (p < 0.005) and 121% greater maximum torque at failure than the controls (p < 0.005), without greater structural stiffness. Evaluation of peak vertical ground reaction forces revealed significantly greater weight-bearing on the experimental limb in dogs with a transverse osteotomy. The results of this relatively short-term study were mixed. Despite the increased structural stiffness of the allograft/endoprosthetic composite with a step-cut osteotomy, the dogs with this type of reconstruction had decreased weight-bearing throughout the course of the study. The step-cut osteotomy may augment the stability of the allograft/endoprosthetic composite, allowing faster healing (as demonstrated by the results of mechanical testing), but in some way, not understood, may cause pain in the reconstructed limb. Longer term studies are needed to answer these questions and to determine whether alteration of the traditional transverse osteotomy has any advantage