Allografts for Skin Closure during In Utero Spina Bifida Repair in a Sheep Model.

Lovepreet K Mann,Jeannine Garnett,Ponnada A Narayana,Eric P Bergh,Ranu Jain,Ramesha Papanna,Rajan Patel,Jong Hak Won,Dejian Lai,Stephen A Fletcher,Meenakshi B Bhattacharjee

doi:10.3390/jcm10214928

Lovepreet K Mann, Jeannine Garnett + Show 9 more

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Objectives: Use of off-label tissue graft materials, such as acellular dermal matrix (ADM), for in utero repair of severe spina bifida (SB), where primary skin layer closure is not possible, is associated with poor neurological outcomes. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties, and provides watertight SB repair. We tested the hypothesis that the HUC is a superior skin patch to ADM for reducing inflammation at the repair site and preserving spinal cord function. Methods: In timed-pregnant ewes with twins, on gestational day (GD) 75, spina bifida was created without a myelotomy (functional model). On GD 95, repair was performed using HUC vs. ADM patches (randomly assigned) by suturing them to the skin edges. Additionally, full thickness skin closure as a primary skin closure (PSC) served as a positive control. Delivery was performed on GD 140, followed by blinded to treatment neurological assessments of the lambs using the Texas Spinal Cord Injury Scale (TSCIS) for gait, proprioception, and nociception. Lambs without spina bifida were used as controls (CTL). Ex vivo magnetic resonance imaging of spines at the repair site were performed, followed by quantitative pathological assessments. Histological assessments (blinded) included Masson’s trichrome, and immunofluorescence for myeloperoxidase (MPO; neutrophils) and for reactive astrocytes (inflammation) by co-staining vimentin and GFAP. Results: The combined hind limbs’ TSCIS was significantly higher in the HUC group than in ADM and PSC groups, p = 0.007. Both ADM and PSC groups exhibited loss of proprioception and mild to moderate ataxia compared to controls. MRI showed increased pathological findings in the PSC group when compared to the HUC group, p = 0.045. Histologically, the meningeal layer was thickened (inflammation) by 2–3 fold in ADM and PSC groups when compared to HUC and CTL groups, p = 0.01. There was lower MPO positive cells in the HUC group than in the ADM group, p = 0.018. Posterior column astrocyte activation was increased in ADM and PSC lambs compared to HUC lambs, p = 0.03. Conclusion: The HUC as a skin patch for in utero spina bifida repair preserves spinal cord function by reducing underlying inflammation when compared to ADM.

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Mid-gestation in utero spina bifida (SB) repair decreases co-morbidities, including shunt placement and ambulation when compared to postnatal repair [1,2]
Lambs transitioned to room air at birth without any difficulties, excepting for a lamb in the human umbilical cord (HUC) repair group that demised within 1 h after delivery for an unknown reason
Upon further analysis following the clinical exclusion of the aforementioned lamb we found that the HUC repair group had a

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Introduction

Mid-gestation in utero spina bifida (SB) repair decreases co-morbidities, including shunt placement and ambulation when compared to postnatal repair [1,2]. In 80% of cases primary skin closure is possible, where the remainder requires tissue grafting [9]. Optimal tissue graft material for skin closure remains unknown. Acellular dermal matrix (ADM) has been used off-label in the pivotal management of myelomeningocele study when primary skin closure could not be achieved [1]. It is a decellularized matrix from human cadaveric skin [1,9]. The effects of ADM use for skin closure compared to primary skin closure remains unknown in terms of subsequent surgeries for tethered cord and the findings of syringomelia [10]

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