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Keywords = Type I collagen nerve conduit

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16 pages, 1962 KB  
Systematic Review
Comparative Outcomes of Direct Versus Connector-Assisted Peripheral Nerve Repair
by Edoardo Agosti, Marco Zeppieri, Tamara Ius, Sara Antonietti, Lorenzo Gelmini, Luca Denaro, Antonella Bonetti, Marco Maria Fontanella, Fulvia Ortolani and Pier Paolo Panciani
Biomedicines 2025, 13(12), 2954; https://doi.org/10.3390/biomedicines13122954 - 30 Nov 2025
Viewed by 624
Abstract
Background: Peripheral nerve injuries affect a significant proportion of patients with upper extremity trauma, with transections frequently requiring surgical intervention. While direct repair (DR) remains the historical standard, connector-assisted repair (CAR) has been proposed to improve functional outcomes by addressing limitations inherent to [...] Read more.
Background: Peripheral nerve injuries affect a significant proportion of patients with upper extremity trauma, with transections frequently requiring surgical intervention. While direct repair (DR) remains the historical standard, connector-assisted repair (CAR) has been proposed to improve functional outcomes by addressing limitations inherent to DR, such as fascicular misalignment and tension at the repair site. Objectives: The purpose of this systematic review is to evaluate and compare the clinical effectiveness and complication rates of DR versus CAR in upper extremity peripheral nerve injuries. Methods: A systematic search of the PubMed, Scopus, and Ovid MEDLINE databases was conducted for clinical studies published between January 1980 and August 2025 that reported sensory outcomes after DR or CAR for peripheral nerve injuries in the upper limb. Studies were included if sensory outcomes could be categorized using the Medical Research Council Classification (MRCC) scale. The primary outcome was the rate of meaningful sensory recovery (MR), defined as MRCC ≥ S3, with a secondary threshold of MRCC ≥ S3+. Secondary outcomes included postoperative neuroma formation, cold intolerance, pain scores, altered sensation, and revision rate. Statistical analysis was performed using two-sided Fisher exact tests and unpaired t-tests, with p < 0.05 considered significant. Results: A total of 441 patients (DR) and 338 (CAR) were included, with mean ages of 34.2 and 37.3 years and a male predominance (79.7% vs. 73.8%). Overall, 705 nerves in DR and 436 in CAR were treated, mainly digital (86.4% vs. 79.9%), followed by ulnar, median, and radial. Sensory nerves predominated (86.4% vs. 81.6%), with mixed nerves more frequent in CAR (22.5%). Most injuries were Grade I (73% vs. 72.1%), with similar rates of Grades II–III. In the CAR group, the most used conduit was collagen type I (58.3%). Sensory recovery (S3+ and S4) was higher in CAR (69.3%) than DR (50.8%), while DR showed lower two-point discrimination >15 mm. Motor recovery was limited, with better values in DR. DASH scores averaged 13.2 (DR) and 18.2 (CAR), with follow-up of 26 and 23.8 months. Complications were more frequent in DR for cold intolerance, altered sensation, and pain, whereas neuromas, revisions, and fistulas were higher in CAR. Conclusions: Connector-assisted repair demonstrates better sensory recovery and less cold intolerance than DR in small-gap upper-extremity nerve injuries but with higher post-interventional risks and costs. DR remains effective for closely approximated nerves. Randomized trials are warranted, as current evidence is heterogeneous and mostly observational. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 1684 KB  
Review
Bridging Gaps in Peripheral Nerves: From Current Strategies to Future Perspectives in Conduit Design
by Elena Stocco, Silvia Barbon, Aron Emmi, Cesare Tiengo, Veronica Macchi, Raffaele De Caro and Andrea Porzionato
Int. J. Mol. Sci. 2023, 24(11), 9170; https://doi.org/10.3390/ijms24119170 - 24 May 2023
Cited by 55 | Viewed by 6074
Abstract
In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance [...] Read more.
In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance®; human origin), and hollow nerve conduits. There are eleven commercial hollow conduits approved for clinical, and they consist of devices made of a non-biodegradable synthetic polymer (polyvinyl alcohol), biodegradable synthetic polymers (poly(DL-lactide-ε-caprolactone); polyglycolic acid), and biodegradable natural polymers (collagen type I with/without glycosaminoglycan; chitosan; porcine small intestinal submucosa); different resorption times are available for resorbable guides, ranging from three months to four years. Unfortunately, anatomical/functional nerve regeneration requirements are not satisfied by any of the possible alternatives; to date, focusing on wall and/or inner lumen organization/functionalization seems to be the most promising strategy for next-generation device fabrication. Porous or grooved walls as well as multichannel lumens and luminal fillers are the most intriguing options, eventually also including the addition of cells (Schwann cells, bone marrow-derived, and adipose tissue derived stem cells) to support nerve regeneration. This review aims to describe common alternatives for severe PNI recovery with a highlight of future conduits. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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19 pages, 4500 KB  
Review
Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair
by Raju Poongodi, Ying-Lun Chen, Tao-Hsiang Yang, Ya-Hsien Huang, Kuender D. Yang, Hsin-Chieh Lin and Jen-Kun Cheng
Int. J. Mol. Sci. 2021, 22(24), 13347; https://doi.org/10.3390/ijms222413347 - 12 Dec 2021
Cited by 75 | Viewed by 10506
Abstract
Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome [...] Read more.
Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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26 pages, 4320 KB  
Article
Modified Hyaluronic Acid-Laminin-Hydrogel as Luminal Filler for Clinically Approved Hollow Nerve Guides in a Rat Critical Defect Size Model
by Zhong Huang, Svenja Kankowski, Ella Ertekin, Mara Almog, Zvi Nevo, Shimon Rochkind and Kirsten Haastert-Talini
Int. J. Mol. Sci. 2021, 22(12), 6554; https://doi.org/10.3390/ijms22126554 - 18 Jun 2021
Cited by 16 | Viewed by 3594
Abstract
Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought [...] Read more.
Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought to improve the regeneration outcome by providing an optimized matrix inside bioartificial nerve grafts. We evaluated here a modified hyaluronic acid-laminin-hydrogel (M-HAL) as luminal filler for two clinically approved hollow nerve guides. Collagen-based and chitosan-based nerve guides were filled with M-HAL in two different concentrations and the regeneration outcome comprehensively studied in the acute repair rat sciatic nerve 15 mm critical defect size model. Autologous nerve graft (ANG) repair served as gold-standard control. At 120 days post-surgery, all ANG rats demonstrated electrodiagnostically detectable motor recovery. Both concentrations of the hydrogel luminal filler induced improved regeneration outcome over empty nerve guides. However, neither combination with collagen- nor chitosan-based nerve guides resulted in functional recovery comparable to the ANG repair. In contrast to our previous studies, we demonstrate here that M-HAL slightly improved the overall performance of either empty nerve guide type in the critical defect size model. Full article
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9 pages, 881 KB  
Article
Collagen Type I Conduits for the Regeneration of Nerve Defects
by Silvan Klein, Jody Vykoukal, Oliver Felthaus, Thomas Dienstknecht and Lukas Prantl
Materials 2016, 9(4), 219; https://doi.org/10.3390/ma9040219 - 23 Mar 2016
Cited by 23 | Viewed by 6100
Abstract
To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve [...] Read more.
To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV), a static two-point discrimination (S2PD) test, and as disability of arm shoulder and hand (DASH) outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS). No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes. Full article
(This article belongs to the Special Issue Regenerative Materials)
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