Fracture nonunion, defined by the U. S. FDA as failure to achieve union within 9 months or absence of radiographic healing progression over three consecutive months, is clinically characterized by persistent localized pain and pseudarthrosis (1). Femoral fracture nonunion specifically manifests as debilitating weight-bearing pain, potential abnormal mobility, and varying degrees of muscular atrophy, severely compromising lower limb function and imposing substantial burdens on patients’ quality of life, families, and society (2, 3).

Current strategies for managing femoral nonunion, as reported in the literature, are broadly categorized into three approaches: (1) Mechanical Stability Optimization: Biomechanical stability remains a prerequisite for healing (1, 4). Techniques include intramedullary nail dynamization, nail exchange, supplementary plate augmentation, combined nail-plate fixation, and external fixation with bone transport, with or without bone grafting. Despite these options, consensus on optimal fixation methods remains elusive (5–8). (2) Biological Augmentation: Enhancing osteogenic potential at the nonunion site is critical, particularly in atrophic cases (4, 9). Strategies include autologous bone grafting (ABG, considered the gold standard), bone morphogenetic proteins (BMPs), demineralized bone matrix (DBM), bone marrow mesenchymal stem cells (BMSCs), platelet-rich fibrin (PRF), and platelet-rich plasma (PRP). This strategy exhibits substantial innovative potential and has garnered significant interest among researchers, emerging as a focal theme in recent nonunion research. However, it currently lacks high-quality studies and robust supportive data (1, 4, 9), particularly regarding platelet-rich plasma (PRP) applications in fracture nonunion. Recent literature over the past 5 years predominantly consists of small case reports (n ≤ 5), underscoring the necessity for large-scale clinical studies to validate its efficacy (9, 10). (3) Non-invasive Interventions: Modalities such as electromagnetic field stimulation, extracorporeal shockwave therapy, ultrasound-guided percutaneous growth factor injection, and traditional Chinese medicine remain controversial in efficacy (1, 4). As an autologous blood product, PRP is enriched with bioactive factors such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and insulin-like growth factor (IGF). It directly or indirectly activates the osteogenic differentiation of mesenchymal stem cells, promotes vascularization, optimizes the microenvironment, exerts anti-inflammatory and immunomodulatory effects, and enhances bone matrix synthesis and mineralization, thereby facilitating the bone tissue repair process (11–13).

Since January 2020, our team has employed dual plate fixation, PRP-augmented autologous grafting, and bioactive core construction for femoral nonunion, achieving favorable clinical outcomes. This study systematically evaluates the efficacy and safety of this biomechanically stable, biologically optimized strategy. Additionally, it aims to provide high-level evidence for PRP application in nonunion treatment and establish a reproducible protocol for PRP utilization in revision surgery.

This single-center retrospective case series, approved by the Ethics Committee of Foshan Hospital of Traditional Chinese Medicine (Approval No.: KY[2024]329), adhered strictly to the Declaration of Helsinki and ethical guidelines. Written informed consent was obtained from all participants. We reviewed cases of aseptic femoral fracture nonunion treated with revision surgery by a senior trauma team between April 2020 and June 2024. Diagnostic criteria followed the U. S. FDA definition: absence of radiographic union within 9 months or lack of healing progression over 3 months. Nonunion types were classified using the Weber-Cech system (hypertrophic, atrophic, oligotrophic). Exclusion criteria: skeletal immaturity, infected nonunion (confirmed histologically), initial open fractures, bone defects >5 cm, non-use of dual plate fixation, absence of PRP-augmented autologous iliac bone grafting (verified via surgical records), failure to construct a bioactive core (documented in records), or incomplete follow-up data. Patients with multiple fractures were excluded. Union criteria: radiographic evidence of ≥3 continuous cortical bone bridges on digital radiographs (DR) and absence of pain at the fracture site during full weight-bearing. Radiographic outcomes included union rates at 9 months post-revision and final follow-up. Clinical metrics encompassed time to union, thigh incision healing duration, pain scores at the nonunion site, lower extremity functional scores, and complications (defined as surgical site infection, incisional exudate/delayed healing, hematoma, heterotopic ossification, or thrombosis).

From 98 initially reviewed medical records, 45 cases were excluded: 25 lacking dual plate fixation, 7 without PRP application, 5 without autologous iliac grafting, 5 infected nonunions, 2 segmental bone defects, and 1 incomplete documentation. Of the 53 included patients, one died in a traffic accident at 5.2 months postoperatively, leaving 52 final participants (35 males, 17 females; mean age 41.38 ± 13.95 years, range 18–69). Nonunion classifications included hypertrophic (19, 36.5%), atrophic (26, 50%), and oligotrophic (7, 13.5%), with 33 femoral shaft (63.5%) and 19 supracondylar (36.5%) cases. All patients completed follow-up (mean 19.01 ± 6.69 months, range 12–45). Baseline characteristics—including interval between initial and revision surgery, injury mechanism, anatomical location, and prior fixation methods—are detailed in Table 1. All 52 patients achieved union (Table 2), with a mean time to clinical and radiographic union of 6.56 ± 1.04 months (range 5–10.3). At 9-month follow-up, 50 patients (96.2%) met union criteria; all achieved union by final follow-up (100%). Representative cases are shown in Figures 3, 4. At initial union confirmation, mean visual analog scale (VAS) pain score was 0.63 ± 0.97 (range 0–5), lower extremity functional score (LEFS) averaged 63.92 ± 5.92 (range 52–76), and thigh incision healing time was 12.13 ± 1.36 days (range 10–16). Postoperatively, 5 patients (9.62%) had complications: 2 donor site discomforts after exercise, 1 femoral vein thrombosis, 1 chronic knee pain (VAS 5), and 1 delayed thigh incision healing (healed day 16). No hematoma or heterotopic ossification occurred. Two patients (3.85%) had serious complications: 1 femoral vein thrombosis (resolved with 1 month oral rivaroxaban) and 1 chronic knee pain (improved with oral diclofenac and topical flurbiprofen gel).

Femoral fracture nonunion, a complication with profound functional implications (2, 3), lacks consensus on optimal management despite numerous reported strategies, with conflicting success rates across methods (5–8). Our protocol—combining dual locking plate fixation for biomechanical stability, PRP-augmented autologous iliac bone grafting, and bioactive core construction—achieved 100% union rates, accelerated healing (mean 6.56 months), excellent pain control (mean VAS 0.63), and functional recovery (mean LEFS 63.92), enabling early rehabilitation. Representative cases are shown in Figures 3, 4.

Current literature reports several internal fixation methods for aseptic femoral fracture nonunion, including intramedullary nail dynamization, nail exchange, combined nail-plate fixation, and dual plating techniques (5–8, 14). Among these, nail exchange has gained considerable favor among researchers (17). Upsizing the intramedullary nail enhances resistance to axial bending forces, improving mechanical stability, while reaming-generated intramedullary cancellous debris and blood flow optimize the local biological environment. This approach is recognized for concurrently offering “mechanical benefits” and “biological benefits” (18, 19). Another common strategy involves augmenting retained or exchanged intramedullary nails with supplementary plates, with or without bone grafting. This nail-plate hybrid construct addresses rotational stability deficiencies inherent to standalone nails. Biomechanical studies (20, 21) demonstrate that hybrid systems exhibit 3.3-fold greater bending and torsional resistance compared to isolated nails. Clinical evidence (19, 22) confirms higher success rates (95–100%) for nail-plate constructs versus nail exchange alone (82.8–91.7%). Despite reported successes with intramedullary nailing, this nail-centric strategy demonstrates limited advantages in treating non-isthmal fractures, extensive bone defects, and atrophic nonunions. Bone defects exceeding 5 mm have been identified as a risk factor for failure of nail exchange (18, 23). Intramedullary nail fixation does not allow sufficient bone grafting, which limits its efficacy in atrophic nonunions (18, 19, 24). This limitation has been corroborated by Özkan et al. (17). Studies also indicate that reaming to accommodate larger-diameter nails damages endosteal vasculature, thereby impairing biological healing processes (25). Placing plates over intramedullary nails makes it challenging to insert adequate bicortical screws (22, 25). Monocortical fixation, due to reduced screw working length, increases the risk of screw cutout and subsequent fixation failure (Figure 5). Intramedullary nailing struggles to achieve satisfactory reduction in cases of malalignment or multiple fracture fragments at the nonunion site (24, 26). The difficulty and failure rate of intramedullary nailing increase when addressing broken screws or fractured nails from prior fixation (27). Additionally, intramedullary nailing is inappropriate for metaphyseal-diaphyseal nonunions and elevates the risk of failure (18). Studies further note that if the initially implanted nail is already of maximum diameter, no larger nail can be provided during revision surgery (14, 28). These limitations highlight the necessity for alternative fixation strategies in complex scenarios, particularly those requiring simultaneous biological optimization and robust mechanical control.

Biomechanical stability is a critical determinant of healing success (1, 4). Biomechanical studies demonstrate that compression plates provide superior tension band structures compared to intramedullary nails (14), with dual plating offering enhanced rotational stability, particularly in non-isthmal fractures (5, 8, 22). Our protocol—dual locking plate fixation combined with structural iliac bone grafting—effectively optimizes biomechanical stability. In a 54-case study (14), authors achieved 100% union rates (mean healing time: 8.23 months) using locking compression plates with autografts (iliac and vascularized fibular bone) for femoral and tibial nonunions. However, their reliance on vascularized fibular grafts increased surgical complexity and required extended remodeling time. In contrast, our technique achieved shorter healing durations with simplified surgical execution. Chamseddine et al. (29) reported successful nonunion management using bridging plates with bone grafting but emphasized aggressive periosteal decortication. Our approach minimized excessive periosteal stripping, reducing associated risks. Wang et al. (5), in a 186-case femoral nonunion series, utilized dual plating with a 4 cm × 1 cm bone trough for graft placement, achieving 98.4% union rates (mean healing time: 7.6 months). While effective, their method involved significant bone sacrifice, which remains controversial in atrophic nonunion management (30). Comparatively, our protocol reduced bone loss and accelerated healing (6.56 months). Similarly, Taheriazam et al. (8) achieved 100% union rates via medullary iliac grafting and dual plating but reported limb shortening in 29.55% of cases. Our technique eliminated this risk. Gavaskar et al. (31) treated 38 cases of distal femoral nonunion with a combination of lateral locking plates, medial anatomical locking plates, and autologous iliac bone grafting, achieving a 91% union rate. The medial anatomical plates addressed the difficulties in distal positioning of the medial condyle and insufficient screw working length caused by non-anatomical implants, but their placement induced knee joint dysfunction and pain, requiring secondary surgery for complication management in 24% of patients. In the study by Lotzien et al. (32), a large augmenting plate was implanted via a medial approach after debridement and bone grafting while retaining the original lateral locking plate. Although a satisfactory union rate was achieved, this technique was associated with substantial surgical trauma and irritation of the medial thigh muscles and soft tissues by the medial plate. In contrast to the above techniques, this study uses anterior-medial placement of a small auxiliary plate without additional surgical incisions, causing less trauma to the medial thigh tissues, improving patient comfort, and facilitating limb functional recovery. These studies collectively affirm that rigid fixation is pivotal for femoral nonunion healing (5, 8, 14, 29, 31, 32). In our series, dual locking plates established a low-strain mechanical environment, optimizing conditions for biological consolidation.

Biological stimulation holds equal importance to biomechanical stability. While biological agents have demonstrated success in nonunion management, robust evidence supporting their superiority over autologous bone grafting—particularly autologous iliac crest bone grafting (AICBG), the current gold standard for atrophic nonunions (1, 4, 9)—remains lacking (9). Reliance solely on ABG may yield inconsistent outcomes (33), prompting clinicians to combine biological agents with ABG. A recent review by the American Academy of Orthopedic Surgeons highlights a 95% success rate with multimodal therapies (30). Commonly used biologics include bone morphogenetic proteins, demineralized bone matrix, and platelet-rich plasma (4, 9). Though FDA-approved for nonunion treatment, BMPs lack conclusive evidence of outperforming AICBG (4, 9, 42). Recent studies increasingly combine BMPs with ABG for fracture nonunion treatment (4, 9). A latest 24-case prospective series (34) reported 100% union rates using rhBMP-2, hydroxyapatite, and autografts for long bone nonunions, suggesting benefits of BMP-AICBG (autologous iliac crest bone grafting) combinations. However, concerns persist regarding BMP-2 antibody-induced adverse immune responses and exuberant bone formation. Despite BMPs’ promise, their application remains contentious (35), with reported drawbacks including high costs and complications such as inflammatory reactions, hematoma, radiculopathy, heterotopic ossification, osteoclast activation, osteolysis, and tumorigenesis (36, 37). A 20-year-old randomized controlled trial (RCT) of 120 cases (38) compared rhBMP-7 and PRP for long bone nonunions, demonstrating superior outcomes with rhBMP-7 (union rate: 86.7% vs. 68.3%; healing time: 8 vs. 9 months). The absence of ABG in the PRP cohort likely contributed to inferior efficacy, as PRP monotherapy underperforms combination approaches (9, 10). Additionally, suboptimal PRP concentrations in that study may have impaired results. Most scholars posit that PRP at 3–6 × baseline platelet levels optimally promotes cellular proliferation, migration, and collagen synthesis, while exceeding 6 × may suppress osteoblast activity (10–12). In our protocol, PRP at 4–5 × baseline concentration enhanced AICBG, yielding safe and superior outcomes. PRP, an autologous blood product, contains concentrated platelets and growth factors—including platelet-derived growth factor (PDGF-aa, PDGF-bb, PDGF-ab), transforming growth factor (TGF-β1, TGF-β2), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These mediators facilitate bone repair and regeneration by stimulating mesenchymal stem cell migration, proliferation, and osteogenic differentiation (11–13).

Choi et al. (34) demonstrated that hydroxyapatite granules and the microporous structure of autologous cancellous bone effectively load BMP, enabling sustained growth factor release. They also constructed a soft tissue template around the nonunion site to guide anatomically conforming bone formation while preventing BMP leakage, termed “conformed bone formation.” Similarly, Nie et al. (16) achieved 93.75% union rates by packing defects with a “putty-like” composite of demineralized bone matrix (DBM) powder mixed with PRP, protected via soft tissue coverage to optimize the regenerative microenvironment. In our protocol, PRP-saturated autologous iliac crest bone grafts utilized cancellous bone’s microporosity (Figure 1F; Figure 2D) to retain substantial PRP volumes, facilitating prolonged bioactive release and enhancing the “bone healing unit’s” potency. Chamseddine et al. (29) achieved 100% union without soft tissue complications using periosteal decortication and tight soft tissue closure to maximize graft-host contact. Our technique sutured viable periosteal and fascial tissues around the nonunion, creating a sealed compartment (Figure 1I) that replicated the “biological chamber” described by Calori and Giannoudis (15), establishing a “maximal bioactive core” central to the diamond concept. PRP within this chamber exerted anti-inflammatory effects. A prospective RCT (39) comparing intra-articular PRP versus saline in pilon fractures reported significantly lower IL-6, IL-8, and PGE2 levels with PRP, alongside elevated IL-1RA, mitigating post-traumatic arthritis risk. Recent studies (40) corroborate concentrated platelet plasma’s ability to accelerate wound healing via fibroblast and endothelial cell migration/proliferation, aligning with Zhang et al.’s (41) findings. Nie et al. (16) further observed reduced incisional complications in PRP cohorts, underscoring its clinical value in inflammation modulation and tissue repair. These advancements underscore the synergistic potential of biomechanical stabilization and targeted biological augmentation in overcoming traditional therapeutic limitations.

In our study, the dual locking plate fixation system established a stable biomechanical environment, while PRP-augmented autologous iliac bone grafting combined with bioactive core construction achieved maximal biological stimulation, accelerating early bone healing and remodeling. This approach enabled earlier functional rehabilitation, potentially reducing complication risks by shortening disability duration (DVT incidence: 1.92%). Functional outcomes, including a mean Lower Extremity Functional Scale (LEFS) score of 63.92 and a pain score of 0.63, confirmed significant quality-of-life improvements.

Notably, current literature on PRP-augmented grafting for femoral nonunion remains scarce (4, 9, 10), precluding direct comparative analysis. As a retrospective study, potential biases—despite mitigation through blinded radiographic assessments (senior orthopedic specialist + two independent radiologists) and functional evaluations by non-affiliated researchers—include selection and assessment biases. Additional limitations include the absence of a control group, lack of nonunion subtype stratification, exclusion of large bone defects (exceeding 5 cm), and variability in PRP preparation protocols. Future research should prioritize biomechanical comparisons between nail-plate and dual plating systems to validate mechanical advantages. Additionally, multicenter randomized trials are needed to define the indications and efficacy of PRP-grafting protocols, especially for large bone defects when combined with ABG. These efforts will refine the stepwise therapeutic framework for traumatic nonunion.

This study validates a safe and effective protocol for femoral nonunion by integrating dual locking plate fixation (providing biomechanical stability) with PRP-augmented autologous iliac grafting and bioactive core construction (enabling growth factor gradient release). The strategy achieved a mean union time of 6.56 months (range: 5–10.3 months), a 3.85% serious complication rate (DVT: 1.92%), and marked functional recovery (mean LEFS: 63.92; pain score: 0.63). Critically, the synergy between mechanical stabilization and biological stimulation not only accelerated healing but also reduced secondary complications by minimizing disability duration, establishing a novel paradigm for restoring limb functional integrity.