Functional polymeric nerve guidance conduits and drug delivery strategies for peripheral nerve repair and regeneration

Manoukian, Ohan S.; Baker, Jiana T.; Rudraiah, Swetha; Arul, Michael R.; Vella, Anthony T.; Domb, Abraham J.; Kumbar, Sangamesh G.

doi:10.1016/j.jconrel.2019.11.021

Cited by 68 publications

(56 citation statements)

References 161 publications

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“…Autologous nerve grafting is currently regarded as the gold standard for reconstruction of nerve damage in the clinic 4 . However, autografts are limited by considerable disadvantages, including poor functional recovery, finite availability, donor site function loss, morbidity, and pain 5 . Nerve guidance conduits (NGCs) have emerged as a potential alternative to autologous nerve grafts due to their ability to reduce neuroma formation and prevent axonal escape 6 - 8 .…”

Section: Introductionmentioning

confidence: 99%

Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration

et al. 2020

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The regenerative capacity of the peripheral nervous system is closely related to the role that Schwann cells (SCs) play in construction of the basement membrane containing multiple extracellular matrix proteins and secretion of neurotrophic factors, including laminin (LN) and brain-derived neurotrophic factor (BDNF). Here, we developed a self-assembling peptide (SAP) nanofiber hydrogel based on self-assembling backbone Ac-(RADA) 4 -NH 2 (RAD) dual-functionalized with laminin-derived motif IKVAV (IKV) and a BDNF-mimetic peptide epitope RGIDKRHWNSQ (RGI) for peripheral nerve regeneration, with the hydrogel providing a three-dimensional (3D) microenvironment for SCs and neurites. Methods: Circular dichroism (CD), atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the secondary structures, microscopic structures, and morphologies of self-assembling nanofiber hydrogels. Then the SC adhesion, myelination and neurotrophin secretion were evaluated on the hydrogels. Finally, the SAP hydrogels were injected into hollow chitosan tubes to bridge a 10-mm-long sciatic nerve defect in rats, and in vivo gene expression at 1 week, axonal regeneration, target muscular re-innervation, and functional recovery at 12 weeks were assessed. Results: The bioactive peptide motifs were covalently linked to the C-terminal of the self-assembling peptide and the functionalized peptides could form well-defined nanofibrous hydrogels capable of providing a 3D microenvironment similar to native extracellular matrix. SCs displayed improved cell adhesion on hydrogels with both IKV and RGI, accompanied by increased cell spreading and elongation relative to other groups. RSCs cultured on hydrogels with IKV and RGI showed enhanced gene expression of NGF, BDNF, CNTF, PMP22 and NRP2, and decreased gene expression of NCAM compared with those cultured on other three groups after a 7-day incubation. Additionally, the secretion of NGF, BDNF, and CNTF of RSCs was significantly improved on dual-functionalized peptide hydrogels after 3 days. At 1 week after implantation, the expressions of neurotrophin and myelin-related genes in the nerve grafts in SAP and Autograft groups were higher than that in Hollow group, and the expression of S100 in groups containing both IKV and RGI was significantly higher than that in groups containing either IKV or RGI hydrogels, suggesting enhanced SC proliferation. The morphometric parameters of the regenerated nerves, their electrophysiological performance, the innervated muscle weight and remodeling of muscle fibers, and motor function showed that RAD/IKV/RGI and RAD/IKV-GG-RGI hydrogels could markedly improve axonal regeneration with enhanced re-myelination and motor functional recovery through the synergetic effect of IKV and RGI functional motifs. Conclusions: We found that the dual-functionalized SAP hydrogels promoted RSC adhesion, my...

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Section: Introductionmentioning

confidence: 99%

Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration

et al. 2020

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“…Collagen is a common structure that is highly concentrated in bone, skin, tendon, and vascular structures, and collagen type I is highly conserved ( Friess, 1998 ) in different species. Collagen is an ideal polymer that may be used to fabricate NGCs because of its low immune response and high absorbability in the body ( Liu et al, 2019 ), and has been commonly utilized as a carrier for drug delivery ( Manoukian et al, 2019b ; Qiu et al, 2020 ). Therefore, collagen is often used to fabricate NGCs for peripheral nerve regeneration.…”

Section: Natural Polymer-based Conduitsmentioning

confidence: 99%

Polymeric Guide Conduits for Peripheral Nerve Tissue Engineering

Jiang

Qian

Fan

et al. 2020

Front. Bioeng. Biotechnol.

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Peripheral nerve injuries (PNIs) are usually caused by trauma, immune diseases, and genetic factors. Peripheral nerve injury (PNI) may lead to limb numbness, muscle atrophy, and loss of neurological function. Although an abundance of theories have been proposed, very few treatments can effectively lead to complete recovery of neurological function. Autologous nerve transplantation is currently the gold standard. Nevertheless, only 50% of all patients were successfully cured using this method. In addition, it causes inevitable damage to the donor site, and available donor sites in humans are very limited. Tissue engineering has become a research hotspot aimed at achieving a better therapeutic effect from peripheral nerve regeneration. Nerve guide conduits (NGCs) show great potential in the treatment of PNI. An increasing number of scaffold materials, including natural and synthetic polymers, have been applied to fabricate NGCs for peripheral nerve regeneration. This review focuses on recent nerve guide conduit (NGC) composite scaffold materials that are applied for nerve tissue engineering. Furthermore, the development tendency of NGCs and future areas of interest are comprehensively discussed.

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“…PNs are particularly vulnerable to injuries caused by mechanical, thermal, compressive or ischemic damages, drug injection injury, and other iatrogenic injuries [10,[24][25][26][27][28][29]. Seddon proposed a classification of nerve damage in the 1940s, defined with 3 levels.…”

Section: Pathology Of Peripheral Nerve Injurymentioning

confidence: 99%

“…After a PN traumatic injury, complex multicellular pathophysiologic changes, including morphologic and metabolic changes, are initiated at the injury site [10,27,[32][33][34]. Changes can be observed in the nerve cell body several hours after the injury, known as chromatolysis, cell body and nucleolar swelling, and nuclear eccentricity (peripheral migration of nuclei).…”

Section: Journal Of Neurorestoratology 255mentioning

confidence: 99%

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The progress of biomaterials in peripheral nerve repair and regeneration

Wang

Zhang²,

et al. 2020

Journal of Neurorestoratology

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Repair and regeneration of the injured peripheral nerve (PN) is a challenging issue in clinics. Although the regeneration outcome of large PN defects is currently unsatisfactory, recently, the study of PN repair has considerably progressed. In particular, biomaterials for repairing PNs, such as nerve guidance conduits and nerve repair membranes, have been well developed. Herein, we summarize the anatomy of the PN, the pathophysiological features of the nerve injury, and the repair process post injury. Then, we highlight the progress in the development of natural and synthetic biomaterials and summarize the applications, advantages, and disadvantages of these materials. These materials can be used as nerve repair membranes and nerve conduits in the field of PN repair. Finally, we discuss the challenges encountered and development strategies for PN repair in the future.

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Functional polymeric nerve guidance conduits and drug delivery strategies for peripheral nerve repair and regeneration

Cited by 68 publications

References 161 publications

Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration

Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration

Polymeric Guide Conduits for Peripheral Nerve Tissue Engineering

The progress of biomaterials in peripheral nerve repair and regeneration

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