Strategies for Treating Traumatic Neuromas with Tissue-Engineered Materials.

Neuroma, a pathological response to peripheral nerve injury, refers to the abnormal growth of nerve tissue characterized by disorganized axonal proliferation. Commonly occurring after nerve injuries, surgeries, or amputations, this condition leads to the formation of painful nodular structures. Traditional treatment options include surgical excision and pharmacological management, aiming to alleviate symptoms. However, these approaches often offer temporary relief without addressing the underlying regenerative challenges, necessitating the exploration of advanced strategies such as tissue-engineered materials for more comprehensive and effective solutions. In this study, we discussed the etiology, molecular mechanisms, and histological morphology of traumatic neuromas after peripheral nerve injury. Subsequently, we summarized and analyzed current nonsurgical and surgical treatment options, along with their advantages and disadvantages. Additionally, we emphasized recent advancements in treating traumatic neuromas with tissue-engineered material strategies. By integrating biomaterials, growth factors, cell-based approaches, and electrical stimulation, tissue engineering offers a comprehensive solution surpassing mere symptomatic relief, striving for the structural and functional restoration of damaged nerves. In conclusion, the utilization of tissue-engineered materials has the potential to significantly reduce the risk of neuroma recurrence after surgical treatment.

Growth factors: Bioactive macromolecular drugs for peripheral nerve injury treatment - Molecular mechanisms and delivery platforms.

Bioactive macromolecular drugs known as Growth Factors (GFs), approved by the Food and Drug Administration (FDA), have found successful application in clinical practice. They hold significant promise for addressing peripheral nerve injuries (PNIs). Peripheral nerve guidance conduits (NGCs) loaded with GFs, in the context of tissue engineering, can ensure sustained and efficient release of these bioactive compounds. This, in turn, maintains a stable, long-term, and effective GF concentration essential for treating damaged peripheral nerves. Peripheral nerve regeneration is a complex process that entails the secretion of various GFs. Following PNI, GFs play a pivotal role in promoting nerve cell growth and survival, axon and myelin sheath regeneration, cell differentiation, and angiogenesis. They also regulate the regenerative microenvironment, stimulate plasticity changes post-nerve injury, and, consequently, expedite nerve structure and function repair. Both exogenous and endogenous GFs, including NGF, BDNF, NT-3, GDNF, IGF-1, bFGF, and VEGF, have been successfully loaded onto NGCs using techniques like physical adsorption, blend doping, chemical covalent binding, and engineered transfection. These approaches have effectively promoted the repair of peripheral nerves. Numerous studies have demonstrated similar tissue functional therapeutic outcomes compared to autologous nerve transplantation. This evidence underscores the substantial clinical application potential of GFs in the domain of peripheral nerve repair. In this article, we provide an overview of GFs in the context of peripheral nerve regeneration and drug delivery systems utilizing NGCs. Looking ahead, commercial materials for peripheral nerve repair hold the potential to facilitate the effective regeneration of damaged peripheral nerves and maintain the functionality of distant target organs through the sustained release of GFs.

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration.

Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials.

Multifunctional wet-adhesive chitosan/acrylic conduit for sutureless repair of peripheral nerve injuries.

The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m-2 ± 30 J m-2, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.

An electroencephalography-based human-machine interface combined with contralateral C7 transfer in the treatment of brachial plexus injury.

Transferring the contralateral C7 nerve root to the median or radial nerve has become an important means of repairing brachial plexus nerve injury. However, outcomes have been disappointing. Electroencephalography (EEG)-based human-machine interfaces have achieved promising results in promoting neurological recovery by controlling a distal exoskeleton to perform functional limb exercises early after nerve injury, which maintains target muscle activity and promotes the neurological rehabilitation effect. This review summarizes the progress of research in EEG-based human-machine interface combined with contralateral C7 transfer repair of brachial plexus nerve injury. Nerve transfer may result in loss of nerve function in the donor area, so only nerves with minimal impact on the donor area, such as the C7 nerve, should be selected as the donor. Single tendon transfer does not fully restore optimal joint function, so multiple functions often need to be reestablished simultaneously. Compared with traditional manual rehabilitation, EEG-based human-machine interfaces have the potential to maximize patient initiative and promote nerve regeneration and cortical remodeling, which facilitates neurological recovery. In the early stages of brachial plexus injury treatment, the use of an EEG-based human-machine interface combined with contralateral C7 transfer can facilitate postoperative neurological recovery by making full use of the brain's computational capabilities and actively controlling functional exercise with the aid of external machinery. It can also prevent disuse atrophy of muscles and target organs and maintain neuromuscular junction effectiveness. Promoting cortical remodeling is also particularly important for neurological recovery after contralateral C7 transfer. Future studies are needed to investigate the mechanism by which early movement delays neuromuscular junction damage and promotes cortical remodeling. Understanding this mechanism should help guide the development of neurological rehabilitation strategies for patients with brachial plexus injury.

Chitin Nerve Conduits with Three-Dimensional Spheroids of Mesenchymal Stem Cells from SD Rats Promote Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) is an unresolved medical problem with limited therapeutic effects. Epineurium neurorrhaphy is an important method for treating PNI in clinical application, but it is accompanied by inevitable complications such as the misconnection of nerve fibers and neuroma formation. Conduits small gap tubulization has been proved to be an effective suture method to replace the epineurium neurorrhaphy. In this study, we demonstrated a method for constructing peripheral nerve conduits based on the principle of chitosan acetylation. In addition, the micromorphology, mechanical properties and biocompatibility of the chitin nerve conduits formed by chitosan acetylation were further tested. The results showed chitin was a high-quality biological material for constructing nerve conduits. Previous reports have demonstrated that mesenchymal stem cells culture as spheroids can improve the therapeutic potential. In the present study, we used a hanging drop protocol to prepare bone marrow mesenchymal stem cell (BMSCs) spheroids. Meanwhile, spherical stem cells could express higher stemness-related genes. In the PNI rat model with small gap tubulization, BMSCs spheres exhibited a higher ability to improve sciatic nerve regeneration than BMSCs suspension. Chitin nerve conduits with BMSCs spheroids provide a promising therapy option for peripheral nerve regeneration.

Targeting silencing androgen receptor gene by shRNA with low-intensity focused ultrasonic irradiation inhibits growth of prostate cancer xenografts in nude mice.

The androgen receptor (AR) plays a pivotal role in prostate cancer, making it a potential therapeutic target. Short-hairpin RNA (shRNA) inhibits gene expression and offers a novel strategy to eradicate disease. Ultrasound-mediated gene transfection is a promising gene delivery method. This study sought to determine whether targeting silencing androgen receptor gene by shRNA with low-intensity focused ultrasonic irradiation could be used as effective therapy for prostate cancers in vivo. A plasmid-based short-hairpin RNA combined with low-intensity focused ultrasonic irradiation approach was used to specifically knock down the expression of AR in prostate cancer 22RV1 cells in vivo. The growth of 22RV1 tumors that had been subcutaneously xenografted was evaluated and expression level of AR was determined by immunohistochemical staining. The proliferative index (PI) and the apoptotic index (AI) were respectively derived from the percentage of positive cells by Ki-67 immunohistochemical staining and TUNEL assay. The plasmid-based AR shRNA administrated intravenously significantly inhibited the tumor growth and AR expression. These inhibitory effects of AR shRNA were augmented when the region of tumor received low-intensity focused ultrasound irradiation. Immunohistochemical staining and TUNEL assay confirmed AR shRNA with low-intensity focused ultrasonic irradiation exhibited growth-inhibitory, antiproliferative, and apoptotic effects on prostate cancer xenografts. The authors showed for the first time that the knockdown of AR expression by plasmid-based AR shRNA with low-intensity focused ultrasonic irradiation significantly suppressed the tumor growth of prostate cancer in vivo.