Alpha1,3-galactosyltransferase knockout does not alter the properties of porcine extracellular matrix bioscaffolds

Liang, Rui; Fisher, Matthew B.; Yang, Guoguang; Hall, Christine; Woo, Savio L‐Y.

doi:10.1016/j.actbio.2011.01.001

Cited by 18 publications

(19 citation statements)

References 61 publications

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“…SIS bioscaffold is mainly composed of collagen type 1 and contains endogenous growth factors such as fibroblast growth factors (FGF) and TGF-β, as well as other chemoattractants which enhances the healing (Hodde et al 1996 ; Hodde et al 2005 ; Voytik-Harbin et al 1997 ). Several studies have shown that SIS can act as a provisional scaffold to promote cell migration and to enhance revascularization and repair (Gilbert et al 2007 ; Liang et al 2008 ; Zantop et al 2006 ; Liang et al 2011 ; Raeder et al 2002 ). It was thus hypothesized that SIS enhances the healing of the ACL and that the SIS-treated ACL is closer to the normal ACL histologically, i.c.…”

Section: Introductionmentioning

confidence: 99%

Histological characteristics of ligament healing after bio-enhanced repair of the transected goat ACL

et al. 2015

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BackgroundRecently, healing of a ruptured anterior cruciate ligament (ACL) is reconsidered. In a previous study, we have shown that the transected ACL can heal after treatment with the triple X locking suture alone or combined with small intestine submucosa (SIS). The first research question of this study was whether the healing ACLs in both groups show histological characteristics that are typical for ligament healing. Secondly, did the combined treatment with SIS lead to improved histological healing, in terms of the morphology of the fibrous synovial layer, the extracellular matrix (ECM), collagen fiber orientation, cellularity, ratio of myofibroblasts, and collagen type 3 staining. The hypothesis was that SIS enhances the healing by the scaffolding effect, endogenous growth factors, and chemoattractants.MethodsIn the Suture group, the left ACL was transected and sutured with the triple X locking suture repair technique. In the Suture-SIS group, the left ACL underwent the same procedure with the addition of SIS. The right ACL served as internal control. Standard histology and immunostaining of α-smooth muscle actin (SMA) and collagen type 3 were used.ResultsMicroscopy showed that the fibrous synovial layer around the ACL was reestablished in both groups. The collagen fibers in the Suture-SIS group stained denser, were more compactly arranged, and the ECM contained fewer voids and fat vacuoles. Neovasculature running between the collagen fibers was observed in both experimental groups. Collagen type 3 stained less in the Suture-SIS group. The cellularity in the Suture group, Suture-SIS group and Control was 1265 ± 1034 per mm2, 954 ± 378 per mm2, 254 ± 92, respectively; 49%, 26% and 20% of the cells stain positive for α-SMA, respectively.ConclusionThe healing ACL in both treated groups showed histological characteristics which are comparable to the spontaneously healing medial collateral ligament and showed that the ACL has a similar intrinsic healing response. Though, no definitive conclusions on the beneficial effects of the SIS scaffold on the healing process can be made.

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Section: Introductionmentioning

confidence: 99%

Histological characteristics of ligament healing after bio-enhanced repair of the transected goat ACL

et al. 2015

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“…SIS is mainly composed of collagen type 1 and contains endogenous growth factors such as FGF and TGF-b and other chemoattractants. [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.…”

Section: Introductionmentioning

confidence: 99%

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

Nguyen

Geel

Schulze

et al. 2013

Tissue Engineering Part A

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Primary suture repair of the anterior cruciate ligament (ACL) has been used clinically in an attempt to heal the ruptured ACL. The results, however, were not satisfactory, which in retrospect can be attributed to the used suturing technique and the suboptimal healing conditions. These constraining conditions can be improved by introducing a new suturing technique and by using small intestinal submucosa (SIS) as a bioscaffold. It is hypothesized that the suturing technique keep the torn ends together and that SIS enhance and promote the healing of the ACL. The goat was used as the study model. In the Suture group, the left ACL was transected and suture repaired with a new locking suture repair technique (n = 5) allowing approximation and fixation under tension. The Suture-SIS group underwent the same procedure with the addition of SIS (n = 5). The right ACL served as control. After 12 weeks of healing, anterior-posterior translation and in situ force of the healing ACL were measured, followed by the measurement of the cross-sectional area and structural stiffness. Routine histology was performed on tissue samples. Gross morphology showed that the healing ACL was continuous with collagenous tissue in both groups. The cross-sectional area of the Suture and the Suture-SIS group was 35% and 50% of the intact control, respectively. The anterior-posterior translations at different flexion angles were statistically not different between the Suture group and the Suture-SIS group. Only the in situ force at 30°in the Suture-SIS group was higher than in the Suture group. Tensile tests showed that the stiffness for the Suture group was not different from the Suture-SIS group (31.1 -8.1 N/mm vs. 41.9 -18.0 N/mm [p > 0.05]). Histology showed longitudinally aligned collagen fibers from origo to insertion. More fibroblasts were present in the healing tissue than in the control intact tissue. The study demonstrated the proof of concept of ACL repair in a goat model with a new suture technique and SIS. The mechanical outcome is not worse than previously reported for ACL reconstruction. In conclusion, the approach of using a new suture technique, with or without a bioscaffold to heal the ACL is promising.

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“…Revivicor, Inc. (Blacksburg, VA) has utilized its expertise in somatic cell nuclear transfer (SCNT), in combination with gene targeting techniques, to establish a unique proprietary genetically engineered (GE) pig, GalSafe®, that has both alleles of GGTA1 inactive, meaning that gal is not detectable in these pigs 71,72 . The GalSafe® pig is phenotypically normal 73,74 to a comparable non-engineered pig except for its genetically engineered trait ( Figure 2). In addition, GalSafe® pigs produce anti-gal IgM and IgG 75 .…”

Section: Establishment Of An Engineered Pig That Does Not Have Galmentioning

confidence: 99%

Alpha-gal syndrome: Implications for cardiovascular disease

Bianchi¹,

Walters²,

Fitch

et al. 2020

gcsp

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Alpha-gal syndrome (AGS) refers to a potentially life-threatening allergy to the molecule galactose-α1,3galactose (gal), which is expressed on most mammalian tissues but, importantly, is not expressed by humans. This syndrome can manifest as an allergic reaction to mammalian meat products, but other sources of mammalian tissue can also provoke an immune response, including injectable and implantable medical products. This syndrome has been linked to coronary atherosclerosis, and medical products that express gal are routinely used in cardiology and cardiac surgery. This article seeks to discuss potential implications of alpha syndrome as it relates to cardiovascular health and to heighten awareness in the cardiovascular community about this emerging public health issue. Prevalence of galactose-α1,3-galactoseMost mammalian species (including New World monkeys, cows, pigs, goats, horses, sheep, rabbits and mice) express the galactose-α1,3-galactose (gal) disaccharide sugar on cells and tissue surfaces 1-4 . Gal expression results from the catalytic activity of the α1,3-galactosyltransferase enzyme encoded by the glycoprotein α1,3galactosyltransferase gene (GGTA1) 1-3, 5 . Certain mammalian species, such as catarrhines (humans, apes, and Old World monkeys), do not have a functional GGTA1 gene 6-8 and correspondingly do not express gal 1, 3, 4 . Additionally, gal has been documented to be absent in fish, amphibians, reptiles, and birds 3,9,10 . The function of gal is unknown 3 , but it is clearly not essential for survival 1, 3 .

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Alpha1,3-galactosyltransferase knockout does not alter the properties of porcine extracellular matrix bioscaffolds

Cited by 18 publications

References 61 publications

Histological characteristics of ligament healing after bio-enhanced repair of the transected goat ACL

Histological characteristics of ligament healing after bio-enhanced repair of the transected goat ACL

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

Alpha-gal syndrome: Implications for cardiovascular disease

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