Ligament Tissue Engineering and Its Potential Role in Anterior Cruciate Ligament Reconstruction

Abstract

Tissue engineering is an emerging discipline that combines the principle of science and engineering. It offers an unlimited source of natural tissue substitutes and by using appropriate cells, biomimetic scaffolds, and advanced bioreactors, it is possible that tissue engineering could be implemented in the repair and regeneration of tissue such as bone, cartilage, tendon, and ligament. Whilst repair and regeneration of ligament tissue has been demonstrated in animal studies, further research is needed to improve the biomechanical properties of the engineered ligament if it is to play an important part in the future of human ligament reconstruction surgery. We evaluate the current literature on ligament tissue engineering and its role in anterior cruciate ligament reconstruction.

Therapeutic Strategies for Tendon Healing Based on Novel Biomaterials, Factors and Cells

“…It is important to obtain the right balance between tissue regeneration and the mechanical properties of the scaffold. Whilst smaller pores are inefficient, larger pores can compromise these mechanical properties [13]. In addition, a scaffold should be easy to handle, store and sterilize.…”

“…Knitting, braiding and electrospinning are the major techniques used for preparation of biomimetic fibrous scaffolds in tendon tissue engineering. When seeded with cells, they spontaneously orientate along the direction of the fibers, leading to abundant ECM secretion rich in collagens I and III [13]. …”

“…FGF-2, TGF-β/BMPs (bone morphogenetic proteins), PDGF (platelet-derived growth factor), EGF (epidermal growth factor), VEGF (vascular endothelial growth factor), IGF (insulin-like growth factor), GDFs (growth and differentiation factors: mainly GDF5, GDF6 and GDF7 [11,12,13]) and HGF (hepatocyte growth factor), have been shown to be necessary for natural healing and have also demonstrated experimental usefulness for tendon repair.…”

Sonographically Guided Anterior Cruciate Ligament Injection: Technique and Validation

“…More specifically, damage to the endo‐ligamentous vasculature limits the influx of endogenous stem cells, platelets, growth factors, and other healing agents, whereas synovial fluid contains plasmin and other factors that may limit fibrin clot formation and the progression of the healing cascade [14,15]. The emergence of regenerative medicine has provided the opportunity to enhance intra‐articular ligamentous healing by overcoming these limitations [9,13,17‐25]. Intra‐articular injections of either unprocessed bone marrow cells or cultured, bone marrow–derived mesenchymal stem cells (MSCs) have been demonstrated to accelerate healing of surgically created partial ACL tears in animal models [9,26].…”

Effect on Ligament Marker Expression by Direct-Contact Co-culture of Mesenchymal Stem Cells and Anterior Cruciate Ligament Cells

“…Scientists in the field of ligament tissue engineering use the expression of Collagen-I, Collagen-III, and Tenascin-C as a tool to evaluate the degree of ligament regeneration. [6][7][8][9]20,21 Microstructurally, close to 94% of ACL tissue is composed of fascicles of collagen fibers, with the remaining 6% comprised of cells and additional extracellular matrix (ECM) components, including Tenascin-C. 22,23 Moreover, *90% of collagen in ACL is type I, with Collagen-III comprising the remaining 10%. 20,22,24 Our objective was to determine the effects of direct co-culture of a variety of ratios of ACLcs and marrow-derived MSCs on the overall expression of ligament markers in vitro as a way to elucidate the optimal cell ratio for future ligament tissueengineering studies.…”