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

Authors

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

Publication Date

10-25-2021

Journal

Journal of Clinical Medicine

Abstract

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,

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.

Keywords

umbilical cord, regenerative healing, sheep spina bifida repair model, inflammation, astrocyte activation, acellular dermal matrix, conventional repair

Comments

PMID: 34768448