Poly(ε-Caprolactone) Nanofiber Wrap Improves Nerve Regeneration and Functional Outcomes after Delayed Nerve Repair

Lopez, Joseph; Xin, Kevin; Quan, Amy; Xiang, Sinan; Barone, Angelo A. Leto; Budihardjo, Joshua; Musavi, Leila; Mulla, Sara; Redett, Richard J.; Martin, Russell; Mao, Hai Quan; Lee, W. P. Andrew; Ibrahim, Zuhaib; Brandacher, Gerald

doi:10.1097/prs.0000000000005715

Cited by 15 publications

(15 citation statements)

References 28 publications

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“…However, there are a few recent studies investigating P(LLA-CL) itself or similar derivates in PNI. They proved effective in improving nerve regeneration of the nerve gap [ 35 , 36 ] or nerve coaptation site wrapping [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Bioactive Nanofiber-Based Conduits in a Peripheral Nerve Gap Management—An Animal Model Study

Dębski

Kijeńska‐Gawrońska

Zołocińska

et al. 2021

IJMS

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The aim was to examine the efficiency of a scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen (COL), polyaniline (PANI), and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model. P(LLA-CL)-COL-PANI scaffold was optimized and electrospun into a tubular-shaped structure. Adipose tissue from 10 Lewis rats was harvested for ASCs culture. A total of 28 inbred male Lewis rats underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In Group A, the nerve gap remained untouched; in Group B, an excised trunk was used as an autograft; in Group C, nerve stumps were secured with P(LLA-CL)-COL-PANI conduit; in Group D, P(LLA-CL)-COL-PANI conduit was enriched with ASCs. After 6 months of observation, rats were sacrificed. Gastrocnemius muscles and sciatic nerves were harvested for weight, histology analysis, and nerve fiber count analyses. Group A showed advanced atrophy of the muscle, and each intervention (B, C, D) prevented muscle mass decrease (p < 0.0001); however, ASCs addition decreased efficiency vs. autograft (p < 0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the groups with the use of conduit (D vs. B p < 0.0001, C vs. B p < 0.001). P(LLA-CL)-COL-PANI conduits with ASCs showed promising results in managing nerve gap by decreasing muscle atrophy.

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Section: Discussionmentioning

confidence: 99%

Bioactive Nanofiber-Based Conduits in a Peripheral Nerve Gap Management—An Animal Model Study

Dębski

Kijeńska‐Gawrońska

Zołocińska

et al. 2021

IJMS

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“…However, there are a few recent studies investigating P(LLA-CL) itself or similar derivates in PNI. They proved effective in improving nerve regeneration of a nerve gap [26,27] or nerve coaptation site wrapping [28]. PCL is also combined with other particles, that may facilitate nerve regeneration, such as laminin [29] graphene [30], carbon nanotubes [31], small porcine intestine submucosa [32].…”

Section: Discussionmentioning

confidence: 99%

Bioactive Nanofiber-based Conduits in a Peripheral Nerve Gap Management- an Animal Model Study.

Dębski

Kijeńska‐Gawrońska

Zołocińska

et al. 2020

Preprint

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Background: Peripheral nerve injuries (PNI) are trauma with severe squeals for patients’ quality of life. Currently, the gold standard of nerve reconstruction relies on primary coaptation. However, in case of a nerve gap, a reconstructive material for bridging is needed. Nerve conduits are an increasingly popular solution alternative to autografts or processed nerved allografts. The aim of the study was to examine the efficiency of a novel bioactive nanofiber-based tubular scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen, polyaniline and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model.Methods: Poly (L-lactic acid)-co-poly(ϵ-caprolactone) scaffold was optimized and enriched with collagen (COL) and polyaniline (PANI) to create final (P(LLA-CL)-COL-PANI), tubular-shaped scaffold, manufactured with electrospinning technology. Parallelly, adipose tissue from 10 Lewis rats was harvested for ASC culture. 28 inbred male Lewis rats were divided into four even groups. Each animal underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In group A, nerve gap remained untouched, in B excised trunk was rotated and used as an autograft, in C nerve stumps were secured with P(LLA-CL)-COL-PANI conduit. In the D group gap was reconstructed with P(LLA-CL)-COL-PANI conduit enriched with ASCs. After 6-months of observation rats were sacrificed. Gastrocnemius muscles (operated and non-operated side) and reconstructed sciatic nerves were harvested for analyses. Muscles were weighted and underwent histological analysis. Nerves were processed and stained immunohistochemically with NF-200 to be analyzed with dedicated software for nerve fiber count. Results: No signs of rejection or excessive fibrosis was noted. Muscle mass ratio was highest in group B (0.77±0.05), then in C (0.74±0,04) and D (0.67± 0.07). Group A showed advanced atrophy of the muscle, each intervention prevented muscle mass decrease (p<0.0001), however, ASC addition decreased efficiency vs autograft (p<0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the group with the use of conduit vs autograft (D vs B p<0.0001, C vs B p<0.001). ASC added to the conduit decreased perineurium hyperplasia.Conclusion: P(LLA-CL)-COL-PANI conduits with ASC showed promising results in managing nerve gap by decreasing muscle atrophy and providing a favorable environment for peripheral nerve regeneration.

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“…Axon regeneration is extensive through conduits composed of fibrin [145,153], hydrogel tubes [154], alginate/chitosan polyelectrolyte [155][156][157], poly epsilon-caprolactone [158,159], polyglycolic acid [160], poly(lactic-co-glycolic acid) or silk-based [161][162][163][164]. Conduits composed of decellularized human umbilical artery [165] and muscles [166] are also effective in promoting axon regeneration across nerve gaps.…”

Section: Conduit Compositionmentioning

confidence: 99%

Restoration of Neurological Function Following Peripheral Nerve Trauma

Kuffler

Foy

2020

IJMS

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Following peripheral nerve trauma that damages a length of the nerve, recovery of function is generally limited. This is because no material tested for bridging nerve gaps promotes good axon regeneration across the gap under conditions associated with common nerve traumas. While many materials have been tested, sensory nerve grafts remain the clinical “gold standard” technique. This is despite the significant limitations in the conditions under which they restore function. Thus, they induce reliable and good recovery only for patients < 25 years old, when gaps are <2 cm in length, and when repairs are performed <2–3 months post trauma. Repairs performed when these values are larger result in a precipitous decrease in neurological recovery. Further, when patients have more than one parameter larger than these values, there is normally no functional recovery. Clinically, there has been little progress in developing new techniques that increase the level of functional recovery following peripheral nerve injury. This paper examines the efficacies and limitations of sensory nerve grafts and various other techniques used to induce functional neurological recovery, and how these might be improved to induce more extensive functional recovery. It also discusses preliminary data from the clinical application of a novel technique that restores neurological function across long nerve gaps, when repairs are performed at long times post-trauma, and in older patients, even under all three of these conditions. Thus, it appears that function can be restored under conditions where sensory nerve grafts are not effective.

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Poly(ε-Caprolactone) Nanofiber Wrap Improves Nerve Regeneration and Functional Outcomes after Delayed Nerve Repair

Cited by 15 publications

References 28 publications

Bioactive Nanofiber-Based Conduits in a Peripheral Nerve Gap Management—An Animal Model Study

Bioactive Nanofiber-Based Conduits in a Peripheral Nerve Gap Management—An Animal Model Study

Bioactive Nanofiber-based Conduits in a Peripheral Nerve Gap Management- an Animal Model Study.

Restoration of Neurological Function Following Peripheral Nerve Trauma

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