Peripheral nerve injuries often lead to long-term disability, and current treatment options offer limited functional recovery. This review is important because it consolidates and critically evaluates the growing body of research on the use of platelet-rich plasma (PRP) as a novel, biologically based therapy for peripheral nerve repair. While PRP has gained attention in various fields of regenerative medicine, its role in nerve healing is still emerging and not yet standardized. By bringing together recent findings from both preclinical and clinical studies, this work provides new insight into how PRP promotes nerve regeneration through anti-inflammatory effects, stimulation of nerve-supporting cells, and delivery of growth factors that accelerate healing. It also explores how PRP can be combined with existing surgical and biomaterial approaches for improved outcomes. This review contributes to the field by highlighting both the therapeutic promise and the current limitations of PRP, and by outlining future research directions needed to optimize its clinical application. As such, it helps define a clearer path forward for integrating PRP into routine nerve injury management.

The central nervous system (CNS), comprising the brain and spinal cord, acts as the central control hub that communicates with various body organs via an extensive network of nerve fibres extending throughout the peripheral nervous system. This communication occurs through electrical and chemical signals that facilitate coordinated physiological functions and responses to environmental stimuli. These peripheral nerves can be systematically classified based on their anatomical locations and functional characteristics into three primary categories: mixed nerves (containing both sensory and motor fibres), motor nerves (responsible for muscle contraction and movement), and sensory nerves (transmitting sensory information from receptors to the CNS) [1, 2].

Peripheral nerve injury (PNI) represents a significant global health concern and a leading cause of long-term disability, affecting millions of individuals worldwide with substantial socioeconomic implications. The consequences of PNI are often devastating, resulting in severe sensory-motor dysfunction that impairs daily activities, chronic neurogenic pain that significantly reduces quality of life, and potential permanent disability requiring long-term rehabilitation [3–5]. The etiology of PNI is diverse and multifactorial, encompassing neurodegenerative diseases that progressively damage nerve structure and function, acute open trauma from accidents or surgical procedures, and chronic nerve compression syndromes such as carpal tunnel syndrome or cubital tunnel syndrome [6, 7].

In the anatomically complex head and neck region, peripheral nerve injuries pose challenges due to the critical functional roles of affected nerves. Damage commonly affects several key cranial and peripheral nerves, including the inferior alveolar nerve (resulting in altered sensation in the lower lip and chin), the lingual nerve (causing taste disturbances and tongue numbness), the facial nerve (leading to facial paralysis and expression difficulties), and the hypoglossal nerve (affecting tongue movement and speech articulation). These injuries can severely impact essential functions such as mastication, speech, facial expression, and overall oral function [8].

While peripheral nerve fibres demonstrate a remarkable regenerative capacity and can achieve spontaneous healing within weeks to months under optimal conditions, this natural recovery process is often incomplete or insufficient, especially in cases involving significant nerve damage, large gaps, or unfavourable local conditions [9]. The clinical reality presents considerable therapeutic challenges, as fewer than half of patients with documented PNI undergo surgical nerve repair, often due to factors such as delayed diagnosis, patient comorbidities, or lack of specialized surgical expertise. Among those who do receive surgical intervention, only 40–50% attain complete functional recovery, highlighting the limitations of current treatment approaches and the urgent need for improved options [10]. Current management strategies include both surgical techniques (such as direct repair, nerve grafting, and nerve transfers) and conservative methods, with non-surgical treatments encompassing targeted physiotherapy programmes, emerging cell-based therapies using stem cells or Schwann cells (SC), and pharmaceutical interventions aimed at managing pain and encouraging nerve regeneration [3–5, 11].

Platelet-rich plasma (PRP) represents an innovative autologous biological therapeutic derived through centrifugal separation of the patient’s own blood, specifically isolating the plasma fraction enriched with platelet concentrations that typically exceed normal physiological levels by 3-5-fold [12, 13]. This preparation process involves collecting whole blood, followed by specific centrifugation protocols that concentrate platelets while preserving their functional integrity and bioactive properties. The resulting PRP product serves as a potent reservoir of endogenous bioactive molecules, being particularly rich in multiple growth factors and cytokines essential for tissue repair and regeneration. These include granulocyte-macrophage colony-stimulating factor (GM-CSF) for cellular proliferation, vascular endothelial growth factor A (VEGF-A) for angiogenesis, epithelial growth factor (EGF) for cellular differentiation, transforming growth factor β (TGF-β) for tissue remodeling, platelet-derived growth factor (PDGF) for cellular migration and proliferation, hepatocyte growth factor (HGF) for neuroprotection, and insulin-like growth factor 1 (IGF-1) for nerve regeneration [14].

PRP has established a substantial clinical track record demonstrating therapeutic efficacy across diverse medical applications, including accelerated healing in sports-related injuries, enhanced recovery in spinal cord trauma, improved wound healing in chronic conditions, and successful outcomes in plastic and reconstructive surgery procedures [15]. Specifically in the context of peripheral nerve injuries, PRP exhibits multifaceted therapeutic mechanisms, demonstrating significant neurogenic properties that promote nerve fibre regeneration, neuroprotective effects that prevent secondary nerve degeneration, and anti-inflammatory activities that modulate detrimental neuroinflammation while creating a favourable microenvironment for healing [8, 16–18]. These comprehensive therapeutic effects are mediated through PRP’s complex role in orchestrating nerve regeneration processes, including SC proliferation, axonal sprouting, remyelination, and its documented capacity to alleviate debilitating neuropathic pain through modulation of inflammatory pathways and pain signaling mechanisms [19]. Compelling clinical evidence continues to emerge supporting PRP’s therapeutic potential, as exemplified by the case study conducted by García de Cortázar et al. [20], who documented satisfactory neurological recovery and functional improvement in a patient with significant nerve injury following a structured PRP treatment protocol administered over 11 months [20].

Given the demonstrated therapeutic potential of PRP in managing peripheral nerve injuries, along with the urgent clinical need for more effective treatment methods to improve functional recovery, this comprehensive review aims to systematically summarize, critically analyze, and discuss current research progress on PRP applications for PNI. The review will evaluate both preclinical and clinical evidence, treatment protocols, outcomes, and future research directions to enhance PRP-based therapies for peripheral nerve injury management.

Accumulating evidence from both preclinical and clinical studies shows that PRP has multiple therapeutic properties vital for peripheral nerve repair. The main reason for PRP’s effectiveness is its ability to regulate neuroinflammation through a dual mechanism involving direct platelet-derived anti-inflammatory mediators and the recruitment of reparative cell populations that release additional anti-inflammatory factors [21–23]. When activated, platelets in PRP release stored anti-inflammatory cytokines such as interleukin-10 (IL-10) and TGF-β, while also attracting macrophages, mesenchymal stem cells, and other regenerative cells to the injury site. These recruited cells further enhance the anti-inflammatory environment by secreting more anti-inflammatory mediators, resulting in a sustained therapeutic effect that lasts beyond the initial platelet activation phase.

Beyond these anti-inflammatory properties, PRP exhibits significant neuroprotective capabilities by preventing secondary neuronal death and promoting axonal survival following peripheral nerve injury. Furthermore, the neurogenic properties of PRP are mediated through the release of neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), which stimulate axonal sprouting, guide nerve fiber growth, and support the maintenance of neuronal phenotype during the regeneration process [1, 24]. Consequently, these growth factors work synergistically to create an optimal microenvironment that facilitates both proximal nerve stump survival and distal target reinnervation.

Building upon these fundamental mechanisms, the therapeutic potential of PRP has been extensively investigated across various peripheral nerve injuries, with consistent positive outcomes reported for multiple anatomical locations. Comprehensive studies have documented PRP’s efficacy in treating injuries to major peripheral nerves, including the sciatic nerve, facial nerve, median nerve, and even applications extending to central nervous system pathologies [1, 21–24]. Moreover, the versatility of PRP treatment is further evidenced by its successful application in diverse clinical scenarios, ranging from complete nerve transection repairs to functional restoration across peripheral nerve gaps [25].

In addition to its regenerative capabilities, PRP therapy has demonstrated significant analgesic properties in treating neuropathic pain associated with peripheral nerve injuries. The pain-relieving mechanisms involve the downregulation of pro-inflammatory cytokines and the modulation of pain signaling pathways at both peripheral and central levels [18, 25–27]. Notably, recent studies have shown that PRP application effectively reduces neuropathic pain in osteoarthritis patients by specifically downregulating microglial activation in the spinal cord, thereby interrupting the central sensitization processes that contribute to chronic pain states [28]. This dual peripheral and central mechanism of pain relief represents a significant advantage over conventional analgesic approaches.

The mechanisms underlying these regenerative effects are significantly mediated through PRP’s impact on Schwann cell biology. SC play a crucial role in peripheral nerve regeneration by providing structural support, producing neurotrophic factors, and facilitating remyelination of regenerating axons. Supporting this understanding, Salarinia et al. [29] demonstrated that PRP treatment significantly enhances SC proliferation in experimental spinal cord injury models in rats, leading to improved functional outcomes. Subsequently, investigations have confirmed PRP’s ability to promote both SC migration to injury sites and their subsequent proliferation, creating a cellular environment conducive to nerve repair [25, 30]. These cellular effects are attributed to the growth factors present in PRP, particularly PDGF and HGF, which specifically target SC receptors and activate proliferation pathways.

Collectively, the diverse applications and mechanisms of PRP in peripheral nerve regeneration have been systematically documented across multiple research studies, with findings consistently supporting its therapeutic value in nerve repair, functional restoration, pain management, and treatment of degenerative neurological conditions [8, 31–36]. The comprehensive body of evidence regarding PRP applications in various peripheral nerve regeneration scenarios is summarized in Figure 1, providing a systematic overview of treatment protocols, outcomes, and clinical effectiveness across different nerve injury types and anatomical locations.

The factors affecting PRP effectiveness are detailed in Table 2 and depicted graphically in Figure 3 for enhanced clarity. The technique used for preparation, the parameters of centrifugation, and patient-specific characteristics such as age and health condition can significantly influence the composition of PRP. Research demonstrates that PRP efficacy decreases with increasing age, with PRP derived from young donors (18–35 years) showing significantly better therapeutic outcomes compared to PRP from older donors (≥65 years) [124]. Studies show that growth factor levels, including PDGF-BB, TGF-β1, IGF-1, and EGF, are statistically higher in subjects younger than 25 years compared to those aged 26 years or older [125]. Additionally, PRP derived from women older than 45 years does not contain significantly higher concentrations of bioactive components compared to younger groups, suggesting that aging significantly affects the active components of PRP [126]. At the cellular level, elderly patients show decreased numbers of α-granules in platelets, which are the main component releasing active substances, leading to decreased platelet function [127]. Clinical evidence supports these laboratory findings, with PRP therapy showing poor efficacy in elderly patients (≥60 years) for conditions such as facial rejuvenation and Achilles tendinitis treatment [124].

The therapeutic efficacy of PRP in peripheral nerve repair demonstrates significant variability due to differences in leukocyte content, growth factor concentrations, and platelet density across various PRP formulations [128–130]. This heterogeneity underscores the critical need for standardized preparation protocols encompassing appropriate anticoagulant selection, optimal centrifugation parameters, and consistent extraction methodologies to ensure reproducible outcomes in both research and clinical applications [131, 132]. Despite encouraging results from preclinical investigations and early-phase clinical trials, the current body of clinical evidence remains insufficient to definitively establish PRP’s effectiveness in nerve repair and regeneration. Existing studies frequently exhibit methodological limitations, including inadequate sample sizes, absence of appropriate control groups, heterogeneous patient populations, and insufficient follow-up durations. Large-scale randomized controlled trials employing standardized protocols and extended observation periods are essential to establish the safety profile, therapeutic efficacy, and optimal clinical applications of PRP therapy in nerve regeneration [133]. Achieving adequate PRP distribution and tissue penetration presents additional complexities, particularly in cases involving scar tissue formation or deep-seated injuries. Anatomical barriers, tissue density variations, and extracellular matrix composition may impede PRP penetration into the neuronal microenvironment, potentially limiting regenerative efficacy. Advanced delivery systems incorporating carrier matrices or bioengineered scaffolds may enhance PRP distribution and retention at nerve injury sites [88]. While PRP therapy generally demonstrates a favorable safety profile, specific risks associated with nerve regeneration applications include hypersensitivity reactions, iatrogenic nerve injury, hematoma formation, and infection. Rigorous adherence to sterile protocols, careful patient selection criteria, and comprehensive adverse event monitoring are essential to minimize these risks and ensure treatment safety [134]. Additionally, therapeutic accessibility remains constrained by economic factors, particularly in regions where insurance coverage or healthcare systems do not support the costs of PRP therapy. Geographic and institutional limitations further compound healthcare disparities. Addressing these challenges requires comprehensive strategies to reduce treatment costs, expand reimbursement coverage, and improve therapeutic accessibility to ensure equitable patient access to this potentially beneficial regenerative approach [110].

The exploration of PRP as a treatment target for PNIs has shown significant promise, especially when PRP is obtained through plasmapheresis. This review emphasizes the positive outcomes seen in both clinical and preclinical studies, where PRP treatment has been linked to better nerve regeneration, improved sensory and motor functions, and less pain. Preclinical studies have provided valuable insights into how PRP promotes nerve repair, including encouraging axonal growth and reducing scar formation. Despite these promising results, several obstacles remain when turning preclinical findings into clinical practice. These include species-specific differences and the need for thorough clinical evaluations to confirm safety and effectiveness in humans. Standardizing PRP preparation methods and optimizing treatment timing are essential steps to improve the consistency and reliability of PRP therapy outcomes. Future research should aim to better understand the molecular mechanisms behind PRP’s therapeutic effects, refine treatment protocols, and expand its clinical use. By tackling these challenges and integrating insights from both human and animal studies, the full potential of PRP as a strong option for nerve regeneration and functional recovery in patients with PNI can be achieved.