Cell outgrowth from the human ACL in vitro: regional variation and response to TGF‐β1

Abstract

One of the new methods being developed to stimulate healing of the human anterior cruciate ligament (ACL) after rupture is the implantation of a biodegradable scaffold which the host cells invade, populate and remodel. One of the cellular behaviors critical to the success of this method is cell outgrowth from the ligament remnants onto an adjacent scaffold. As morphological differences have been previously reported in the proximal and distal human ACL, the primary aim of this study was to determine if the cells from the proximal and distal ACL had different outgrowth behaviors as well. A second aim was to determine whether TGF-PI, reported to be a mitogen for fibroblasts, would affect the outgrowth behaviors from the proximal and distal ACL. To achieve these aims, explants from both the proximal and distal human ACL were placed into culture under various conditions and outgrowth measured for 42 days. In explants cultured with lo'%, fetal bovine serum (high serum group) the explants from the proximal ACL had an earlier start of outgrowth than the distal explants 0, < 0.015), and outgrowth rates were similar in the two groups. In explants cultured with 2% fetal bovine serum (low serum group), the explants from the proximal ACL had an earlier start to outgrowth 0, < 0.003) as well as a faster rate of outgrowth (p < 0.004) than the distal explants. The addition of TGF-PI to the low serum cultures significantly slowed the rate of outgrowth from both groups of ACL explants 0, < 0.025). These results suggest that outgrowth behaviors are different in the proximal and distal human ACL, and that TGB-PI has an inhibitory effect on cell outgrowth from ACL explants. However, this study is only a first step, and additional experiments are needed to further optimize tissue engineering parameters for enhancement of the repair of the ACL.

Characterization of Transcript Levels for Matrix Molecules and Proteases in Ruptured Human Anterior Cruciate Ligaments

“…It may be possible however to promote an increase in cell activity comparable to that of young, early injury patients through application of appropriate mechanical and biochemical milieu to ACL fibroblasts in vitro [12,36,37]. The marker expression level observed in the current study could provide an initial template for the development and refinement of such an engineering approach.…”

Collagen‐platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament

“…These results support our hypothesis that an important mechanism for failure of the ACL to heal is a lack of appropriate provisional scaffold. 24,25,38 This is a critical finding as prior research into stimulation of healing in intraarticular tissue defects has focused on overcoming cellular deficiencies, [14][15][16]18,19,26,27,[39][40][41][42][43][44] rather than scaffolding deficiencies. 26 In this study, no cells (except the platelets and white blood cells contained in the collagen-PRP hydrogel) were transplanted, yet a highly cellular repair tissue was seen within the defect after only 4 weeks.…”

Telomere length of anterior crucial ligament after rupture: Similar telomere length in injured and noninjured ACL portions

“…As our data revealed no differences between the three different ACL parts, we suggest that other factors such as low cellularity, low vascularity, insufficient fibrin-platelet scaffold after injury, and inadequate release of cytokines and growth factors are potential causes of the low healing capacity of ACL. 2,15,[34][35][36] Importantly, telomere length in the injured ACL portion was not altered by the occurrence of the major steps of ligament repair including the intense phase of pro-liferation. Based on our findings, we hypothesize that one event of ACL rupture and repair does not cause a long-term impairment of tissue regenerative potential.…”