Nerve Capping with Porcine Extracellular Matrix Constrains Disorganized Axonal Regrowth: Preliminary Evidence from a Human Nerve Injury Model
6 affiliations
- 1Department of Neurosurgery, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA
- 2School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- 3Department of Orthopaedic Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- 4Department of Health Sciences, College of Health Sciences, Rush University, Chicago, IL 60612, USA
- 5Department of Hand and Microvascular Surgery, University Medical Center, Lubbock, TX 79415, USA
- 6Division of Plastic and Reconstructive Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Abstract
Peripheral nerve injuries that lack a distal target are prone to symptomatic neuroma formation, yet durable, low-complexity solutions remain limited. We report the first clinical evaluation of a porcine submucosa large-diameter nerve cap (PSLDNC) with paired human histology, contextualized by a previously published preclinical rat study. A 49-year-old man with a mangled hand underwent partial hand amputation with median nerve stump capping using a 7-mm PSLDNC. Eight months later, during revisional trans-radial amputation, the original cap was explanted for histopathology and the median, ulnar, and superficial radial nerves were recapped. Clinically, both residual limb pain and phantom limb pain fell from 39/100 pre-revision to 0 by six and three months, respectively, and remained absent through 15 months; the patient discontinued gabapentin and demonstrated excellent prosthetic function (BAM-ULA 10/10). Histology of the explant showed organized micro-fascicular architecture with minimal collagen deposition and only mild axonal swirling; NF immunostaining demonstrated directional alignment and higher neurofilament density within the capped segment (2326 vs. 945 µm2 per 10,000 µm2 in a patient control). In that referenced study, capped nerves exhibited fully organized architecture by 12 weeks (axonal swirling score = 0), significantly greater NF-positive area than uncapped controls, minimal local tissue reactivity, and lower pain-related behavioral scores. Together, the human clinical course, human explant histology, and animal histology are consistent with a mechanism in which PSLDNCs confine and guide regenerating axons, allow space for exhaustion of axonal outgrowth, and limit aberrant outgrowth and fibrosis, alongside meaningful relief of neuroma-related pain. Because this is a single patient whose revision also included neuroma resection, nerve re-capping, and intramuscular burial of the stumps, the contribution of the cap cannot be isolated; the absence of an uncapped histologic control and of a clinical comparator further tempers inference. Nonetheless, these data support nerve capping as a feasible, technically straightforward adjunct for neuroma prevention and symptom control, meriting prospective, controlled evaluation and longer-term follow-up.
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BibTeX
@article{sakthiyendran2026nerve,
title = {{Nerve Capping with Porcine Extracellular Matrix Constrains Disorganized Axonal Regrowth: Preliminary Evidence from a Human Nerve Injury Model}},
author = {Naveen Arunachalam Sakthiyendran and Caroline J. Cushman and Evan J. Hernandez and Anceslo Idicula and Ian L. Valerio and Brendan J. MacKay},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211924},
url = {https://www.mdpi.com/2073-4409/15/21/1924},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nerve Capping with Porcine Extracellular Matrix Constrains Disorganized Axonal Regrowth: Preliminary Evidence from a Human Nerve Injury Model
AU - Naveen Arunachalam Sakthiyendran
AU - Caroline J. Cushman
AU - Evan J. Hernandez
AU - Anceslo Idicula
AU - Ian L. Valerio
AU - Brendan J. MacKay
PY - 2026
DA - 2026/10/23
JO - Cells
DO - 10.3390/cells15211924
UR - https://www.mdpi.com/2073-4409/15/21/1924
AB - Peripheral nerve injuries that lack a distal target are prone to symptomatic neuroma formation, yet durable, low-complexity solutions remain limited. We report the first clinical evaluation of a porcine submucosa large-diameter nerve cap (PSLDNC) with paired human histology, contextualized by a previously published preclinical rat study. A 49-year-old man with a mangled hand underwent partial hand amputation with median nerve stump capping using a 7-mm PSLDNC. Eight months later, during revisional trans-radial amputation, the original cap was explanted for histopathology and the median, ulnar, and superficial radial nerves were recapped. Clinically, both residual limb pain and phantom limb pain fell from 39/100 pre-revision to 0 by six and three months, respectively, and remained absent through 15 months; the patient discontinued gabapentin and demonstrated excellent prosthetic function (BAM-ULA 10/10). Histology of the explant showed organized micro-fascicular architecture with minimal collagen deposition and only mild axonal swirling; NF immunostaining demonstrated directional alignment and higher neurofilament density within the capped segment (2326 vs. 945 µm2 per 10,000 µm2 in a patient control). In that referenced study, capped nerves exhibited fully organized architecture by 12 weeks (axonal swirling score = 0), significantly greater NF-positive area than uncapped controls, minimal local tissue reactivity, and lower pain-related behavioral scores. Together, the human clinical course, human explant histology, and animal histology are consistent with a mechanism in which PSLDNCs confine and guide regenerating axons, allow space for exhaustion of axonal outgrowth, and limit aberrant outgrowth and fibrosis, alongside meaningful relief of neuroma-related pain. Because this is a single patient whose revision also included neuroma resection, nerve re-capping, and intramuscular burial of the stumps, the contribution of the cap cannot be isolated; the absence of an uncapped histologic control and of a clinical comparator further tempers inference. Nonetheless, these data support nerve capping as a feasible, technically straightforward adjunct for neuroma prevention and symptom control, meriting prospective, controlled evaluation and longer-term follow-up.
SN - 2073-4409
ER -