Representative tissue sections taken from the midsubstance region of control normal tissue (Sham) and scar tissues (Saline, GH, IGF-I, GH+IGF-I). The longitudinal axis of the ligament is from the top left to bottom right of each image (200X). Tissues from sham control (Sham) animals have the characteristic crimp pattern and aligned fibroblasts associated with normal tissue. Examination of scar tissue from ambulatory healing animals (Amb + Sal) revealed typical scar morphology with matrix disorganization and hypercellularity. In contrast to ambulatory animals, hindlimb unloaded (HU + Sal) animals showed abnormal scar formation with pockets of cell clusters and misaligned collagen fibers creating defects and voids by not connecting. Examination of extracellular matrices from GH treated animals revealed no improvement in matrix organization in tissues from ambulatory (Amb + GH) or hindlimb unloaded (HU + GH) animals. However, animals treated with IGF-I showed extensively increased matrix density and substantially improved matrix alignment in tissues from ambulatory (Amb + IGF) and hindlimb unloaded (HU + IGF) animals; indicating a considerable improvement in the matrix structure in animals treated with IGF-I. Animals that were treated with both GH and IGF-I showed similar improvement to that seen with IGF-I in unloaded tissues (HU + GH + IGF) but showed no improvement in ambulatory tissues (Amb + GH + IGF).