The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three‐dimensional collagen‐GAG scaffold

Abstract

Our work focuses on development of a collagen-glycosamimoglycan (CC) scaffold to facilitate ligament healing in the gap between the ruptured ends of the human anterior cruciate ligament (ACL). In the present investigation, we evaluated the effects of selected growth factors on human ACL cell responses important in tissue regeneration, namely cell migration, proliferation, collagen production, and expression of a-smooth muscle actin (SMA).Methods: Explants from six human ACLs were cultured on top of a CG scaffold. Culture conditions were with either 2% FBS (control), or 2% FBS supplemented with TGF-01, PDGF-AB, EGF, or FGF-2. Histologic cell distribution, total DNA content, proliferation rate, rate of collagen synthesis, scaffold diameter and percentage of SMA positive cells were determined at two, three and four weeks.Results: The addition of TGF-01 to the culture medium resulted in increased cell number, increased collagen production and increased expression of SMA within the scaffold. Supplementation with PDGF-AB resulted in increased cell proliferation rates within the scaffold and increased collagen production. The addition of FGF-2 resulted in increased cell proliferation rates and slowed rates of scaffold shrinkage when compared with the control group.Discussion: This work suggests that certain growth factors can alter the biologic functions of human ACL cells in a CG scaffold implanted as a bridge at the site of an ACL rupture. Based on these findings, the addition of selected growth factors to an implantable CG scaffold may facilitate ligament healing in the gap between the ruptured ends of the human ACL.

Proliferation of anterior cruciate ligament cells in vitro by photo‐immobilized epidermal growth factor

“…[19][20][21][22] Cell growth and collagen proliferation were observed in vitro in ACL and MCL cultured with growth factors such as basic fibroblast growth factor (b-FGF), transforming growth factor-b (TGF-b), platelet-derived growth factor (PDGF), and EGF. 10,13 In an in vivo experiment with b-FGF, new vessels invaded injury sites in less time, thereby accelerating the overall healing process.…”

Prediction of Growth Factor Effects on Engineered Cartilage Composition Using Deterministic and Stochastic Modeling

“…Again, k is the carrying capacity of the collagen molecules in engineered cartilage constructs (noted as K 2 in the text). The steady state probability density function for GAG accumulation as a fraction of construct carrying capacity under the simulated variability of growth factor (described by equation 20), where λ 1 = 1/187, 36 and ℜ 1 = 0.05. The steady state probability density function for collagen deposition as a fraction of construct carrying capacity under the simulated variability of growth factor (described by equation 21), where λ 2 = 1/18.9, 36 and ℜ 2 = 0.2.…”

“…1 Meaney Murray et al 20 observed that a number of selective growth factors could remarkably increase the collagen production in ECM. Both in vivo and in vitro experiments show that some growth factors enhance the production of biomolecules and some inhibit it.…”

Recent Applications of Polymeric Biomaterials and Stem Cells in Tissue Engineering and Regenerative Medicine

“…Collagen has found widespread use as a scaffold and carrier for cells in various tissue engineering applications, specifically, soft tissue applications such as skin 16,17 and cartilage. 18,19 Natural carbohydrates have been utilized as hydrogels not only for drug delivery, but also for tissue engineering. 20 Among these, the linear glycosaminoglycan hyaluronic acid (HA), which is composed of repeating disaccharide units of glucuronic acid and N-acetylglucosamine, is widely distributed in the ECM and critical to vertebrate tissue morphogenesis.…”