Enhancing Nerve Regeneration and Functional Rehabilitation: A Comprehensive Analysis of TCM and Novel Biomaterials

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Peripheral nerve injuries (PNI) represent a significant medical challenge, often leading to lifelong disability. Effective rehabilitation after PNI involves two crucial aspects: promoting nerve regeneration and preventing muscle atrophy. Traditional Chinese Medicine (TCM) techniques, such as acupuncture, Tuina, and microneedles, have shown potential in facilitating nerve repair and functional recovery by promoting axon regeneration and activating Schwann cells.

However, the underlying molecular mechanisms of these TCM methods remain largely unexplored, hindering their broader application. Concurrently, novel biomaterials, including hydrogels, microfluidic platforms, and chitosan scaffolds, have emerged as promising tools for treating nerve injuries. This article delves into the synergistic potential of integrating TCM rehabilitation techniques with novel biomaterials, aiming to provide a scientific foundation for more effective and precise treatments for PNI.

The peripheral nervous system (PNS) comprises nerve tissues located outside the brain and spinal cord. Injuries to peripheral nerves often result in severe neuropathic pain and dysfunction, affecting approximately 13 to 23 individuals per 100,000 annually. Common causes of PNI include trauma, ischemia, and infections. Effective rehabilitation after PNI focuses on two main goals: promoting nerve regeneration and preventing muscle atrophy due to denervation.

Schwann cells (SCs) play a pivotal role in the PNS, aiding in the myelination of axons and facilitating nerve regeneration by removing myelin debris and necrotic tissue at injury sites. Despite the inherent regenerative capacity of PNS axons, achieving satisfactory outcomes remains challenging due to excessive macrophage aggregation, prolonged denervation, and subsequent muscle atrophy. Therefore, exploring new clinical treatment strategies to enhance nerve regeneration and prevent muscle atrophy is a primary research focus.

Efficacy of Chinese Medicine Rehabilitation in Peripheral Nerve Injury

TCM rehabilitation techniques have gained attention for their potential benefits in treating PNI. Key methods include Tuina, acupuncture, and microneedles.

Tuina

Tuina, a classical TCM therapy, involves various maneuvers such as pushing, rolling, squeezing, pressing, and joint movements. Research indicates that Tuina can effectively slow down muscle atrophy and promote nerve regeneration. In rat models with sciatic nerve injury, Tuina has been shown to relieve pain, maintain motor function, and enhance brain plasticity by promoting adaptive changes in the somatosensory cortex. The therapy’s effectiveness is attributed to its ability to regulate muscle-specific microRNA expression, stimulate muscle satellite cell proliferation, and promote autophagy, which helps remove damaged organelles and proteins, providing substrates and energy for muscle fiber regeneration.

Tuina’s therapeutic effects also involve the mechanically gated ion channel Piezo1, which converts mechanical signals into biochemical reactions that promote cell differentiation and regulate apoptosis. Studies suggest that Tuina manipulation activates Piezo1, reducing apoptosis and maintaining skeletal muscle calcium homeostasis, thereby mitigating muscle injury.

Acupuncture

Acupuncture is widely recognized for its regulatory effects on peripheral nerve injuries. By selecting specific acupoints and techniques, acupuncture can promote nerve excitation, reduce inflammation, improve blood circulation, and accelerate nerve function recovery. The therapeutic mechanisms involve several signaling pathways:

  • Notch Signaling Pathway: Acupuncture activates the Notch pathway, which is crucial for SC activation and nerve myelin regeneration. Increased expression of the Notch intracellular domain (NICD) facilitates SC activation and stem cell differentiation, promoting nerve repair.
  • MAPK Pathway: Acupuncture inhibits the nuclear translocation of NF-κB p65 and the expression of p38MAPK, reducing inflammation and improving nerve repair by down-regulating key targets in the TLR4/MAPKs/NF-κB signaling pathway.
  • Wnt Signaling Pathway: Acupuncture up-regulates the expression of Wnt1 and Wnt3a, inhibiting β-catenin phosphorylation and ubiquitination, thus promoting stem cell proliferation and differentiation for nerve regeneration.

Although acupuncture’s clinical efficacy in PNI rehabilitation is well-documented, the mechanisms remain partially understood. Future research should focus on standardizing acupuncture protocols and exploring the intricate molecular interactions involved.

Microneedles

Microneedles, traditionally used in TCM for neurological disorders, have evolved into minimally invasive drug delivery devices. Comprising neatly arranged micro-needles, they can deliver drugs to the subcutaneous area safely and painlessly. Types include solid, coated, hollow, and dissolvable microneedles, with dissolvable microneedles offering superior biocompatibility and controlled drug release. While microneedles alone may not suffice for PNI rehabilitation, combining them with novel biomaterials enhances their therapeutic potential by improving neuronal synaptic adsorption and promoting neuronal network construction.

Efficacy of Novel Biomaterials in Peripheral Nerve Injury

PNI treatments often require innovative approaches, particularly for larger nerve defects. Novel biomaterials offer promising solutions for nerve regeneration and functional recovery.

Nerve Guidance Conduits (NGCs)

NGCs, made from natural, synthetic, or semi-synthetic biomaterials, provide physical channels for nerve regeneration. These conduits support cell growth, allow nutrient diffusion, and eliminate metabolic waste, making them viable alternatives to autogenous nerve grafts. Advances in NGC design include biomimetic constructs, scaffold modifications, and surface modifications to enhance repair effects and promote nerve regeneration.

Silk Fibroin (SF)

SF is a high-biocompatibility tissue engineering material. Studies have shown that SF electrospun fibers can effectively bridge nerve gaps, promoting axonal regeneration and functional recovery in animal models. TENGs with SF have demonstrated consistent therapeutic effects comparable to autogenous nerve transplants, highlighting their potential for clinical applications.

Chitin Scaffolds

Chitin scaffolds, combined with small autogenous nerves and platelet-rich plasma, have shown significant potential in promoting sciatic nerve regeneration and reducing muscle atrophy. Acellular cauda equina allografts (ACEA), composed of chitin conduits and decellularized horse tails, offer effective alternatives to autogenous transplants for treating long-distance nerve defects.

Microfluidic Chips

Microfluidic platforms enable the construction of in vitro models for high-throughput, quantitative evaluation of PNI treatments. These models facilitate real-time monitoring of neuronal behavior and provide insights into nerve regeneration mechanisms. Microfluidic technology is instrumental in simulating the neural microenvironment, supporting stem cell differentiation, and enhancing the precision of therapeutic evaluations.

Synergistic Potential of TCM Rehabilitation and Novel Biomaterials

Combining TCM techniques with novel biomaterials can enhance the precision and efficacy of PNI treatments. For instance, integrating Tuina with hydrogels that regulate the mechanical microenvironment of peripheral nerves can amplify therapeutic effects. Similarly, combining acupuncture with advanced biomaterials, such as graphene-based sensors, can improve real-time monitoring and therapeutic outcomes.

Innovative applications, such as using microneedle patches for drug delivery in combination with hydrogel-based acupoint burial, offer new methods for targeted, continuous drug delivery with fewer side effects. These approaches underscore the potential of integrating traditional TCM therapies with cutting-edge biomaterials to address the complex challenges of PNI rehabilitation.

In conclusion, the integration of TCM rehabilitation techniques with novel biomaterials represents a promising frontier in the treatment of peripheral nerve injuries. By combining the therapeutic strengths of both approaches, it is possible to enhance nerve regeneration, prevent muscle atrophy, and improve the overall quality of life for patients with PNI. Continued research and development in this interdisciplinary field are essential for realizing the full potential of these innovative treatment strategies.


referencee link :https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1421772/full


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