Long-term effects of porcine small intestine submucosa on the healing of medial collateral ligament: A functional tissue engineering study

Abstract

Porcine small intestinal submucosa (SIS) was previously shown to enhance the mechanical properties of healing medial collateral ligaments (MCL), and the histomorphological appearance and collagen type V/I ratio were found to be close to those of normal MCL. We hypothesized that at a longer term, 26 weeks, SIS could guide a better organized neo-ligament formation, increasing mechanical properties and increasing collagen fibril diameters mediated by a reduction in collagen type V. A 6 mm gap injury in the right MCL was surgically created in 38 rabbits, while the contralateral intact MCL served as a sham-operated control. In half the animals, a strip of SIS was sutured onto the severed ends. In the other half, no SIS was applied. The cross-sectional area (CSA) was determined with a laser micrometer system. The femur-MCL-tibia complex was mechanically tested in uniaxial tension. Histomorphology was determined through H&E and immunofluorescent staining and transmission electron microscopy (TEM). Sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to determine collagen type V/I ratio. SIStreated MCLs displayed a 28% reduction in CSA, a 33% increase in tangent modulus, and a 50% increase in tensile strength compared with the nontreated group ( p < 0.05). TEM showed groups of collagen fibrils with larger diameters in the SIS-treated ligaments in comparison with uniformly small fibrils for the nontreated group. H&E staining showed more densely stained collagen fibers in the SIS-treated group aligned along the longitudinal axis with more interspersed spindle-shaped cells. Immunofluorescent staining showed less collagen type V signals, confirmed by a 5% lower ratio of collagen type V/I compared with the nontreated controls ( p < 0.05). The findings extend the shorter term 12-week results, and support the potential of porcine SIS as a bioscaffold to enhance ligament healing. ß

Healing of the Goat Anterior Cruciate Ligament After a New Suture Repair Technique and Bioscaffold Treatment

“…[17][18][19] Several studies have shown that SIS can provide a collagenous matrix to promote cell migration into the healing site to enhance revascularization and repair. [20][21][22][23][24] It is hypothesized that SIS enhance and promote the healing of the ACL. Instead of using the SIS as a load-bearing 10-layered bioscaffold, like in the rotator cuff repair, only a single layer of SIS was used to recruit sufficient healing cells to the hypocellular ACL.…”

Tissue-Engineered Extracellular Matrices (ECMs) as Adjuvant Scaffolds for Endovascular Aneurysmal Repair (EVAR)

“…A rapid remodelling response can occur once infiltrating host cells selforganise and begin producing their own ECM. This results in a time dependent return to expected mechanical strength and site-appropriate mechanical behaviour after xenogenic implantation (S. , Liang et al 2006.…”

Use of a bioscaffold to improve healing of a patellar tendon defect after graft harvest for ACL reconstruction: A study in rabbits

“…25,26 When a single layer of SIS was applied to a gap injury of the rabbit medial collateral ligament (MCL), the healing ligament had better collagen fiber alignment with larger collagen fibril diameters. 22,23 Also, the mechanical properties of the healing MCL were significantly improved with a 33% increase in tangent modulus and a 50% increase in tensile strength.…”

“…[16][17][18] An extracellular matrix derived bioscaffold, namely the porcine small intestinal submucosa (SIS), has been successfully used to enhance the repair of ligaments and tendons. [19][20][21][22][23] SIS possesses unique properties including a preferentially aligned collagen type I matrix which is thought to provide contact guidance for the healing cells. Additionally, SIS contains a variety of growth factors capable of attracting healing cells through chemotaxis.…”