Abstract
Background
This study represents the largest single-center cohort to date evaluating the early- and mid-term safety and effectiveness of a staged reconstructive strategy using 3D-printed microporous titanium prostheses, applied either alone or in combination with free flap reconstruction, for the management of infected bone defects.
Methods
Patients treated between January 2019 and January 2025 were retrospectively identified from electronic medical records. Primary outcomes included changes in Visual Analogue Scale (VAS) scores and Lower Extremity Functional Scale (LEFS) scores at 3, 6, and 12 months, as well as at the last follow-up. Secondary outcomes included implant integration, postoperative functional recovery milestones for lower-extremity cases, and complication profiles.
Results
This study included 80 consecutive patients (54 males, 26 females) with an average age of 47.5 ± 9.3 years and an average follow-up time of 40.8 ± 14.8 months. At follow-up time points of 3 months and beyond, VAS scores significantly decreased compared to preoperative levels (p < 0.0001), and lower extremity LEFS scores significantly improved (p < 0.0001). At 12 months postoperatively, 69 cases (86.3%) were rated as “Excellent” in terms of implant integration. Subgroup analyses demonstrated that both the single microporous titanium group and the combined free flap group experienced significant improvements in pain relief, functional scores, and postoperative lower-extremity functional recovery over time. Eight patients reported complications, including 6 cases of recurrent infection and 2 cases of prosthesis or screw fractures. A history of diabetes and mixed bacterial infections were significantly associated with a higher risk of recurrent infection (p < 0.05).
Conclusions
Preliminary evidence suggests that both the single porous titanium group and the combined free flap group exhibited sustained pain relief and continuous improvement in lower-limb function, with relatively low complication rates. Relying on advanced microsurgical techniques to obtain free flaps and implementing stratified treatment for diabetic patients are crucial for orthopedic surgeons.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12891-026-09665-5.
Keywords: Microporous Titanium, 3D Printed, Infected Bone Defects, Free Flap, Clinical Outcomes
Introduction
Infected bone defects are common and serious complications following trauma, osteomyelitis, and revision surgeries, particularly when large bone defects of the limbs are accompanied by soft tissue damage [1]. These bone defects often lead to recurrent infections due to the loss of mechanical support, persistent infection, and insufficient soft tissue coverage [2]. Traditional treatments such as autologous bone grafting, the Masquelet technique, and Ilizarov bone transport face challenges such as long treatment cycles, a high incidence of complications (with infection recurrence rates ranging from 15% to 30%), and limited functional recovery [3–5].
In recent years, 3D-printed customized titanium alloy prostheses have provided a new direction for bone defect reconstruction after infection control, thanks to their advantages in precise anatomical matching, immediate mechanical stability, and microporous structure that promotes bone ingrowth [6, 7]. The clinical application of 3D-printed microporous titanium in orthopedics initially began with the repair and reconstruction after bone tumor resection and limb-salvage surgeries, achieving favorable results [8]. In osteomyelitis treatment, given the complexity and high cost of traditional Masquelet and Ilizarov bone transport techniques, personalized 3D printing technology can promote bone-prosthesis interface integration and bone ingrowth through porosity, while maintaining good mechanical support [9]. Furthermore, soft tissue defects associated with complex cases remain a key factor limiting their effectiveness. The lack of well-vascularized soft tissue coverage significantly increases the risk of prosthesis exposure and recurrent infection [10]. For the repair of soft tissue defects of varying degrees, free flap techniques (such as the anterolateral thigh free flap) can effectively reduce dead space, promote wound healing, and reduce the risk of deep infection by providing well-vascularized tissue coverage [11, 12].
Current research on the treatment of infected bone defects primarily focuses on single treatment strategies, such as prosthesis implantation or local pedicled flap repair. For example, Liu et al. [13] reported on the use of 3D-printed microporous titanium implants for treating infected bone defects caused by osteomyelitis, with 6 out of 8 patients achieving good bone integration. We also reported the use of single microporous titanium prosthesis implantation for treating 18 patients with infected bone defects caused by osteomyelitis, with 17 patients (94.4%) achieving good healing [14]. Previously, in 2022, we first reported the preliminary efficacy of free/local flaps combined with 3D-printed microporous titanium for treating 6 cases of lower limb infected bone defects with soft tissue loss, with 5 patients achieving good wound healing (83.3%) [15]. Additionally, Chen et al. [16] used local transposition flaps combined with 3D-printed microporous titanium to treat 13 patients with femoral bone defects following osteomyelitis, achieving good bone integration and wound healing in 7 cases during follow-up. However, the personalized harvesting of free flaps and the advantages of covering large soft tissue defects are not addressed in existing studies. On the other hand, current research is limited to lower limb cases, with a lack of evidence for the efficacy in upper limb infected bone defects. Importantly, these clinical efficacy and safety data have not been validated in large-scale studies.
The biomechanical performance of the 3D-printed microporous titanium prosthesis has been systematically evaluated in our previous study using integrated biomechanical testing and finite element analysis, which demonstrated sufficient load-bearing capacity, favorable stress distribution, and resistance to fatigue failure [17]. Building on this biomechanical foundation, we conducted the largest single-center retrospective cohort study to date to evaluate the clinical safety and effectiveness of a staged reconstructive strategy incorporating personalized 3D-printed microporous titanium prostheses for infected bone defects. This strategy integrates individualized prosthesis implantation with free flap reconstruction when required, allowing its application to infected bone defects with varying degrees of soft tissue involvement at different anatomical locations in the limbs (Fig. 1). In addition to assessing overall clinical outcomes, we explored risk factors associated with postoperative complications. Patients were further stratified into subgroups according to the presence or absence of significant soft tissue defects, namely a single prosthesis group and a combined free flap group. Rather than aiming to compare these subgroups for superiority, subgroup analyses were performed to characterize clinical features and recovery trajectories across different tiers of reconstructive complexity, thereby evaluating the applicability and universality of the staged treatment protocol. The staged approach consisted of: (1) infection control with or without individualized free flap coverage based on soft tissue requirements; and (2) definitive bone reconstruction using a customized 3D-printed microporous titanium prosthesis.
Fig. 1.
This is the first report of combining free flap technique with personalized 3D-printed microporous titanium strategy for the clinical outcomes of infected bone defects and soft tissue defects in different parts of the limbs
Materials and methods
Study design
This is a retrospective study. Our institution specializes in the treatment of infected bone defects caused by various factors and has extensive experience in limb repair and reconstruction. After approval from the institutional ethics review board (2019-018-02), we conducted a retrospective data collection and analysis of a series of patients who underwent microporous titanium implant treatment from January 2019 to January 2025. This cohort study has been reported in line with the STROCSS guidelines [18, 19].
Patient selection
The inclusion criteria were as follows: (1) For bone defect characteristics, patients with infected nonunion or traumatic bone defects in the limbs (including tibia, femur, humerus, radius, carpal bones, metacarpal bones, and metatarsal bones, etc.) where the bone defect length after debridement could not be repaired by traditional autologous or artificial bone grafts (confirmed by imaging measurements and 3D CT reconstruction); (2) Patients with concomitant soft tissue defects that could not be closed by direct suturing or skin grafting (evaluated by wound measurement software or intraoperative sterile film method); (3) Postoperative follow-up ≥ 3 months with complete imaging (X-ray/CT) and laboratory data. Additionally, the study excluded the following: (1) Severe uncontrolled underlying diseases (such as uncontrolled diabetes: HbA1c > 8%, heart failure grade III-IV, cirrhosis Child-Pugh class C) (2), Long-term use of immunosuppressants or corticosteroids (prednisone ≥ 10 mg/d, continuous use for > 3 months); (3) Tumor-related bone destruction (primary bone tumors or metastatic tumors), radiation-induced bone necrosis, congenital skeletal deformities; (4) Loss to follow-up or missing critical data (imaging, functional scores). All surgeries were performed by the same senior surgeon to reduce heterogeneity in the procedure.
Surgical technique and postoperative rehabilitation
This study employed a two-stage surgical approach to treat complex infected bone defects. Prior to the second surgery, a 3D CT scan was used to assess the morphology of the bone defect and the extent of soft tissue involvement, after which an individualized 3D-printed microporous titanium prosthesis was custom-designed (pore diameter 700–750 μm, porosity 65–75%). The first-stage surgery involved thorough debridement, removal of necrotic bone and soft tissue, and the implantation of vancomycin-loaded bone cement (2 g vancomycin/40 g bone cement). Simultaneously, a free anterolateral thigh flap was used to repair the concomitant soft tissue defect in 25 cases. Postoperatively, antibiotic treatment based on bacterial culture results was administered until the infection was completely controlled (CRP, ESR, and white blood cell counts normalized for two consecutive tests). In the second-stage surgery, the induced membrane was preserved, bone cement was removed, and the pre-designed microporous titanium prosthesis was implanted (secured by intramedullary protrusion anchor and titanium plate fixation). The surface of the prosthesis was coated with vancomycin sulfate calcium. Regardless of whether the procedure involved a single implantation or a combined free flap repair, all patients received standardized nursing and rehabilitation. Detailed information regarding staged surgery and postoperative rehabilitation can be found in Supplemental Material 1, including first-stage surgery, postoperative management, design and manufacturing of 3D-printed microporous titanium prosthesis, and second-stage surgery and postoperative rehabilitation.
Data collection and outcome measures
Outpatient follow-up and data collection were performed at baseline and at 3, 6, and 12 months postoperatively, with annual reviews thereafter. All follow-up data were collected and organized by research assistants, and electronic medical records were reviewed, including case files, surgical details, laboratory, and imaging data. The baseline data obtained for patients included age, gender, and medical history; primary characteristics included etiology (traumatic or non-traumatic) of the bone defect, location, length, soft tissue defect area, flap type, and bacterial culture results.
Laboratory and imaging assessments (X-ray and CT) were performed preoperatively and at 3, 6, and 12 months postoperatively, with subsequent annual checks. Visual analogue scale (VAS) scores [20] were recorded at each follow-up. CRP and ESR were measured at each follow-up time point, and infection control was considered achieved if the values normalized for two consecutive tests (CRP < 10 mg/L, ESR < 20 mm/h). Additionally, implant integration and stability were evaluated using X-ray and CT examinations. Successful implant integration was defined by fulfillment of all of the following criteria: (1) progressive trabecular bone formation at the bone–prosthesis interface; (2) absence of progressive radiolucent lines greater than 2 mm; and (3) absence of implant migration, loosening, or mechanical failure. Failure to meet any one of these criteria was classified as poor implant integration.
For lower limb cases, postoperative functional recovery was assessed using the Lower Extremity Functional Scale (LEFS) [21], recording the postoperative standing time, walking time with crutches, and time to full weight-bearing. Infection eradication was assessed based on a comprehensive evaluation combining clinical, laboratory, and radiological criteria. Clinical signs included the absence of sinus tract, persistent drainage, local erythema, swelling, or pain. Additionally, pre-defined complications included wound recurrent infection, flap necrosis, poor wound healing, prosthesis-related infections, prosthesis-related fractures, implant fractures, and non-union.
Statistical analysis
Data analysis was performed using IBM SPSS (version 29.0). For baseline data, continuous variables were presented as mean ± standard deviation or median (interquartile range) and categorical variables were expressed as frequency (percentage). Differences in LEFS and VAS scores before and after surgery were analyzed using Wilcoxon signed-rank tests. Predefined complications (such as recurrent infection, prosthesis fracture, etc.) were treated as binary outcome variables. Univariate logistic regression was performed to assess the relationship between patients’ baseline characteristics (age, gender, bone defect length, etc.) and surgical features (flap repair, bacterial type, etc.). Odds ratios (OR) and 95% confidence intervals (CI) were calculated. A p-value of < 0.05 was considered statistically significant.
Results
Baseline characteristics
From February 2019 to January 2025, 82 patients with osteomyelitis caused by trauma or non-trauma underwent staged surgeries. All patients signed an informed consent form for surgery. Two patients were excluded because they did not undergo the second-stage surgery after the first debridement and vancomycin-loaded implant. In the end, 80 patients met the eligibility criteria and were included in the analysis. Among these, 54 were male (67.5%) and 26 were female (32.5%), with an average age of 47.5 ± 9.3 years, an average BMI of 26.6 ± 2.9 kg/m², and an average follow-up time of 40.8 ± 14.8 months. The majority of infected bone defects were traumatic (52 cases, 65%). There were 24 patients with a history of hypertension, 10 with a history of diabetes, and 4 with both hypertension and diabetes. The median bone defect length was 11.4 cm (range 3.8–32.0 cm), and the soft tissue defect area ranged from approximately 5.0 × 8.0 cm to 33 × 10 cm (Table 1). None of the 80 patients lost to follow-up at the last visit.
Table 1.
Baseline Patient Characteristics
| Characteristics | Overall (N = 80)* | Single Microporous Ttitanium (N = 55)* | Combined Free Flap (N = 25)* | P value# |
|---|---|---|---|---|
| Age (years)† | 47.5 (9.3) | 47.0 (7.8) | 48.5 (12.1) | 0.582 |
| Sex (male)‡ | 54 (67.5%) | 37 (67.3%) | 17 (68%) | 0.949 |
| BMI (kg/m2) | 26.6 (2.9) | 26.2 (2.6) | 26.7 (3.4) | 0.07 |
| Lesion etiology | ||||
| Traumatic | 52 (65.0%) | 39 (70.9%) | 13 (52%) | 0.100 |
| Non-traumatic | 28 (35.0%) | 16 (29.1%) | 12 (48%) | |
| Past history | ||||
| Diabetes | 10 (12.5%) | 6 (10.9%) | 4 (16%) | 0.523 |
| Hypertension | 24 (30%) | 16 (29.1%) | 8 (32%) | 0.792 |
| Diabetes and hypertension | 4 (5%) | 1 (1.9%) | 3 (12%) | 0.167 |
| Bone defect length (cm)§ | 11.4 (8.5–15.5) | 10.5 (8.3–15.0) | 12.0 (9.5–18.0) | 0.132 |
| Bone defect location | ||||
| Femur | 11 (13.8%) | 11 (20%) | / | NA |
| Tibia | 51 (63.8%) | 32 (58.2%) | 19 (76%) | 0.124 |
| Humerus | 5 (6.3%) | 5 (9%) | / | NA |
| Radius | 4 (5%) | 4 (7.3%) | / | NA |
| Metatarsal | 3 (3.8%) | / | 3 (12%) | NA |
| Carpal | 6 (7.5%) | 3 (5.5%) | 3 (12%) | 0.567 |
| Metacarpal | 6 (7.5%) | 3 (5.5%) | 3 (12%) | 0.567 |
| Soft tissue defect area range (cm) | 5.0 × 8.0–33 × 10 | / | 5.0 × 8.0–33 × 10 | NA |
| Bacterial culture | ||||
| Staphylococcus aureus | 50 (62.5%) | 36 (65.5%) | 14 (56%) | 0.418 |
| Staphylococcus epidermidis | 12 (15%) | 7 (12.7%) | 5 (20%) | 0.398 |
| Pseudomonas aeruginosa | 9 (11.25%) | 5 (9.1%) | 4 (16%) | 0.600 |
| Escherichia coli | 4 (5%) | 4 (7.3%) | / | NA |
| Mixed infection | 5 (6.25%) | 3 (5.4%) | 3 (12%) | 0.567 |
| Postoperative follow-up duration (months)** | 40.8 (14.8) | 42.8 (12.3) | 36.4 (15.5) | 0.073 |
*N = Number of patients. †Values are presented as mean ± standard deviation.‡Values for qualitative data are presented as frequency (percentage).§Values are presented as median, with interquartile range in parentheses. #Chi-square test, t-test, and Kruskal-Wallis test were used for group comparisons of categorical variables, normally distributed continuous variables, and non-normally distributed continuous variables, respectively. **Follow-up time is from the initial surgery to the time of inclusion. NA = not applicable
Among the 55 cases in the single microporous titanium implant group, 37 were male (69.1%) and 18 were female (30.9%), with an average age of 47.0 ± 7.8 years and an average follow-up time of 42.8 ± 12.3 months. The range of soft tissue defect area was approximately 5.0 cm × 8.0 cm to 33 cm × 10 cm. The median bone defect length was 10.5 cm (range 3.5–28.0 cm), including 32 cases of tibial bone defects, 11 cases of femoral bone defects, 5 cases of humeral bone defects, 4 cases of radial bone defects, and 3 cases of combined carpal and metacarpal bone defects. In the free flap combined group, there were 25 cases, with 17 males (68.0%) and 8 females (32.0%), with an average age of 48.5 ± 12.1 years and an average follow-up time of 36.4 ± 15.5 months. The median bone defect length was 12.0 cm (range 3.8–32.0 cm), including 3 cases with extensive dorsal foot soft tissue defects accompanied by large segments of metatarsal bone defects, 19 cases with lower leg soft tissue defects accompanied by large segments of tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal and carpal bone defects.
The bacterial culture results from the first-stage surgery showed that among the 25 patients in the free flap combined group, Gram-positive (G⁺) infections accounted for 76% (19/25), primarily Staphylococcus aureus (14/25) and Staphylococcus epidermidis (5/25). Gram-negative (G⁻) infections accounted for 16% (4/25), all due to Pseudomonas aeruginosa. Mixed infections (Staphylococcus aureus + Pseudomonas aeruginosa) accounted for 8% (2/25). For the 55 cases in the single microporous titanium implant group, G⁺ infections accounted for 78.2% (43/55), with Staphylococcus aureus being the predominant pathogen (65.5%, 36/55), followed by coagulase-negative staphylococci (Staphylococcus epidermidis in 7 cases). G⁻ infections accounted for 14.5% (8/55), including Pseudomonas aeruginosa (4/9) and Escherichia coli (4/9). Mixed infections accounted for 7.3% (4/55), with Staphylococcus aureus + Pseudomonas aeruginosa in 3 cases, and Staphylococcus aureus + Escherichia coli in 1 case.
Overall clinical efficacy
The average baseline VAS score preoperatively was 7.2 ± 1.4, which decreased to 1.6 ± 0.7 at 12 months postoperatively. The VAS score at the last follow-up was 1.2 ± 0.4 (Table 2). At each postoperative follow-up time point (3 months, 6 months, 12 months, and the last follow-up), VAS scores significantly decreased (p < 0.0001). For lower limb cases (N = 65), the average baseline LEFS score preoperatively was 28.5 ± 5.8, with significant improvements in the LEFS score at each follow-up time point (3 months, 6 months, 12 months, and the last follow-up) (p < 0.0001). The average time to first standing for lower limb patients was 2.1 ± 0.5 months, the average time to first walking with crutches was 3.8 ± 1.1 months, and the average time to full weight-bearing was 5.3 ± 0.9 months. Based on the implant integration by X-ray and CT examinations, the number of cases rated as “Excellent” and “Poor” were 69 (86.3%) and 11 (13.7%), respectively. The representative case is shown in Fig. 2.
Table 2.
Distribution of Key Follow-up Indicators (VAS, LEFS, postoperative standing time, crutch walking time, and Radiographic implant integration)
| Outcome Indicators | Overall (N=80) | Single Microporous Ttitanium (N=55) | Combined Free Flap (N=25) |
|---|---|---|---|
| VAS pain | |||
| Preoperative | 7.2 (1.4) | 7.0 (1.5) | 7.6 (1.2) |
| Postoperative | |||
| Month 3 | 4.8 (0.8) † | 4.7 (0.8) † | 5.0 (0.7) † |
| Month 6 | 2.4 (1.0) † | 2.3 (1.1) † | 2.6 (0.7) † |
| Month 12 | 1.7 (0.7) † | 1.5 (0.6) † | 1.9 (0.9) † |
| Final follow-up | 1.2 (0.4) † | 1.2 (0.9 to 1.5) † | 1.3 (1.0 to 1.7) † |
| LEFS (N=65) | |||
| Preoperative | 28.5 (5.9) | 29.3 (5.3) | 26.8 (6.8) |
| Postoperative | |||
| Month 3 | 38.5 (7.5) † | 39.5 (6.4) † | 38.0 (7.9) † |
| Month 6 | 54.5 (9.8) † | 56.8 (9.6) † | 49.6 (8.7) † |
| Month 12 | 59.0 (57 to 62) † | 60.6 (6.4) † | 55.0 (7.7) † |
| Final follow-up | 60.0 (58.0 to 63.0) † | 60.5 (4.0) † | 59.0 (3.2) † |
| Postoperative standing time (N=65) | 2.1 (0.5) | 2.0 (0.6) | 2.3 (0.5) |
| Crutch walking time (N=65) | 3.8 (1.1) | 3.5 (1.1) | 4.2 (1.2) |
| Full weight-bearing time (N=65) | 5.3 (0.9) | 5.1 (0.7) | 5.8 (1.1) |
| Radiographic implant integration | |||
| Excellent | 69 (86.3%) | 50 (90.9%) | 19 (76%) |
| Poor | 11 (13.7%) | 5 (9.1%) | 6 (24%) |
*t-test and Kruskal-Wallis test were used for comparisons of normally distributed and non-normally distributed continuous variables, respectively. †Compared with baseline data, outcome indicators at 3 months, 6 months, 12 months, and at the last follow-up showed statistically significant differences (P < 0.0001)
Fig. 2.
Reconstruction of a left tibial comminuted fracture with extensive soft tissue loss. A. A 52-year-old male patient sustained a left tibial comminuted fracture due to a car accident. Prior to admission, bone cement was used for filling, and external fixation was applied. B. After sufficient infection control, an anterolateral thigh free flap was harvested from the opposite side to repair the skin defect on the lower leg, and vancomycin-loaded bone cement was used for filling. C. In the second-stage surgery, a 3D-printed microporous titanium prosthesis was used to repair the tibial defect, with the surface coated with vancomycin tricalcium phosphate. D. At 1-year postoperative follow-up, the patient’s lower leg appearance, X-ray, and CT images are shown
Subgroup analysis
In the single microporous titanium implant group (N = 55), the average baseline VAS score preoperatively was 7.0 ± 1.5. At each follow-up time point, VAS scores significantly decreased (p < 0.0001; Fig. 3). For lower limb cases (N = 43), the average baseline LEFS score preoperatively was 29.2 ± 5.2, with significantly higher scores observed at each follow-up time point (3 months, 6 months, 12 months, and the last follow-up) (p < 0.0001). The average time to first standing for lower limb patients was 2.0 ± 0.6 months, the average time to first walking with crutches was 3.5 ± 1.1 months, and the average time to full weight-bearing was 5.1 ± 0.7 months. Based on the implant integration by X-ray and CT examinations, the number of cases rated as “Excellent” and “Poor” were 50 (90.9%) and 5 (9.1%), respectively.
Fig. 3.
Plots of the VAS pain scores. Both the single microporous titanium group and the combined free flap group showed significant improvement in pain compared to baseline VAS scores at 3 months, 6 months, 12 months, and the last follow-up time point (p < 0.0001)
For the free flap combined group (N = 25), the average baseline VAS score preoperatively was 7.6 ± 1.2. At each follow-up time point, VAS scores significantly decreased (p < 0.0001; Fig. 4). For lower limb cases (N = 22), the average baseline LEFS score preoperatively was 27.1 ± 6.7, with significantly higher scores observed at each follow-up time point (3 months, 6 months, 12 months, and the last follow-up) (p < 0.0001). The average time to first standing for lower limb patients was 2.3 ± 0.5 months, the average time to first walking with crutches was 4.2 ± 1.2 months, and the average time to full weight-bearing was 5.8 ± 1.1 months. For implant integration, the number of cases rated as “Excellent” and “Poor” were 19 (76%) and 6 (24%), respectively.
Fig. 4.
Plots of the LEFS pain scores. Both the single microporous titanium group and the combined free flap group showed significant improvement in pain compared to baseline LEFS scores at 3 months, 6 months, 12 months, and the last follow-up time point (p < 0.0001)
Complications
A total of 8 complications occurred during the postoperative follow-up period among 80 patients, resulting in an overall complication rate of 10% (Table 3). The complications were categorized as recurrent infections and prosthesis fractures, occurring at an average of 7.5 ± 3.6 months postoperatively. Among these, recurrent infection was the most common complication (7.5%), occurring at an average of 5.8 ± 3.1 months postoperatively. Prosthesis fracture occurred in 2.5% of cases, with an average onset at 11.5 months postoperatively. Notably, the tibia was the most common site of complications, accounting for 50% of all complications. Specifically, in the single 3D-printed microporous titanium prosthesis group, two patients experienced recurrent tibial infections at 6 and 11 months postoperatively. After debridement, vancomycin-loaded bone cement was implanted, and both patients resumed walking at 6- and 8-months post second-stage surgery, respectively. One patient developed a recurrent infection at 5 months postoperatively, and after debridement and implantation of vancomycin-loaded bone cement, walking was restored 6 months post second-stage surgery. Another patient in the same group experienced a femoral prosthesis fracture at 13 months postoperatively, which was followed by prosthesis removal and implantation of vancomycin-loaded bone cement, with walking restored 7 months after the second-stage surgery. In the free flap combined treatment group, two diabetic patients developed foot wound infections at 3 and 4 months postoperatively. Both patients underwent prosthesis removal and replacement with vancomycin-loaded bone cement, with walking restored at 5- and 7-months post second-stage surgery, respectively. One patient developed a recurrent tibial infection at 8 months postoperatively, and after debridement and implantation of vancomycin-loaded bone cement, walking was restored 4 months after the second-stage surgery. Another patient had a tibial fixation prosthesis screw fracture at 10 months postoperatively. After revision surgery, walking was restored 5 months later, with no recurrence of infection observed.
Table 3.
Distribution of Postoperative Complications
| Complications | Overall (N = 80) | Single Microporous Ttitanium (N = 55) | Combined Free Flap (N = 25) | P value* |
|---|---|---|---|---|
| Total no. (%) with complications | 8 (10%) | 4 (7.3%) | 4 (16%) | 0.421 |
| Recurrent infection† | 6 (7.5%) | 3 (5.5%) | 3 (12%) | 0.567 |
| Femur | 1 (1.25%) | 1 (1.8%) | / | NA |
| Tibia | 3 (3.75%) | 2 (3.6%) | 1 (4%) | 1.000 |
| Foot | 2 (2.5%) | / | 2 (8%) | NA |
| Prosthesis fracture | 2 (2.5%) | 1 (1.8%) | 1 (4%) | 1.000 |
| Femur | 1 (1.25%) | 1 (1.8%) | / | NA |
| Tibia | 1 (1.25%) | / | 1 (4%) | NA |
*Chi-square test was used for group comparisons of categorical variables. †Pathogens remaining in the body re-proliferate, leading to the recurrence of clinical manifestations. NA not applicable
Risk factors of complications
Exploratory risk factor analysis (Table 4) showed that diabetes mellitus was associated with a higher occurrence of postoperative complications in both univariate logistic regression (OR = 11; p = 0.004) and Fisher’s exact test (p = 0.007). The increased risk of recurrent infection was associated with a history of diabetes (OR = 9.571; p = 0.013) and bacterial culture results showing mixed infection (OR = 8.75; p = 0.031). No significant associations were observed between other baseline characteristics and prosthesis-related mechanical failure. However, given the small number of events, these findings should be interpreted with caution.
Table 4.
Risk Factors Associated with Postoperative Complications
| Variables | Any Complications | Recurrent Infection | Prosthesis Fracture | |||
|---|---|---|---|---|---|---|
| OR (95% CI, P value) | Fisher’s exact test (P value) | OR (95% CI, P value) | Fisher’s exact test (P value) | OR (95% CI, P value) | Fisher’s exact test (P value) | |
| Sex | ||||||
| Male | ||||||
| Female | 0.247 (0.054, 1.128); 0.071 | 0.105 | 0.212 (0.036, 1.241); 0.085 | 0.084 | 0.472 (0.028, 7.853); 0.601 | 0.547 |
| BMI | ||||||
| 28 kg/m2 | ||||||
| <28 kg/m2 | 0.583 (0.110, 3.087); 0.526 | 0.707 | 0.911 (0.157, 5.287); 0.917 | 1.000 | NA | NA |
| Lesion etiology | ||||||
| Traumatic | ||||||
| Non-traumatic | 0.887 (0.196, 4.018); 0.876 | 1.000 | 2.872 (0.319, 25.886); 0.347 | 0.659 | NA | NA |
| Diabetes | ||||||
| Yes | ||||||
| No | 11.000 (2.180, 55.494); 0.004 | 0.007 | 9.571 (1.615, 56.736); 0.013 | 0.024 | 7.667 (0.440, 133.540); 0.162 | 0.236 |
| Hypertension | ||||||
| Yes | ||||||
| No | 1.457 (0.319, 6.655); 0.627 | 0.691 | 1.182 (0.201, 6.932); 0.853 | 1.000 | 2.391 (0.143, 39.887); 0.544 | 0.513 |
| Bone defect length | ||||||
| 10 cm | ||||||
| <10 cm | 1.800 (0.339, 9.561); 0.49 | 0.704 | 1.149 (0.197, 6.692); 0.877 | 1.000 | NA | NA |
| Staphylococcus aureus infection | ||||||
| Yes | ||||||
| No | 0.565 (0.130, 2.451); 0.446 | 0.465 | 0.271 (0.046, 1.579); 0.146 | 0.109 | NA | NA |
| Mixed infection | ||||||
| Yes | ||||||
| No | 5.667 (0.855, 37.567); 0.072 | 0.108 | 8.750 (1.215, 62.989); 0.031 | 0.042 | NA | NA |
OR odds ratio, CI confidence interval, NA not applicable
Discussion
In this study, the most significant finding was that 90% of patients did not experience recurrence after receiving either single microporous titanium implantation or combined free flap treatment, with an average follow-up of 40.8 months. The postoperative 1-year VAS score significantly decreased from 7.2 ± 1.4 to 1.6 ± 0.7 (p < 0.0001), and the LEFS score for the lower limbs increased from 28.5 ± 5.8 to a median score of 59.0 (p < 0.0001). The implant integration was rated as “Excellent” in 86.3% of cases. Additionally, we found that a history of diabetes and mixed bacterial infections may be important risk factors for recurrent infections.
Over the past few decades, both the Masquelet and Ilizarov techniques have been clinically applied as important treatment options for infected bone defects [22, 23]. However, the effectiveness of these methods may be compromised by complications such as pin tract infections, donor site infections, non-union, mechanical issues, or even recurrent fractures [24, 25]. Many patients are unable to bear weight during the early postoperative recovery period. For example, a previous clinical efficacy comparison analysis showed that the average fixation time for the Masquelet and Ilizarov groups was 10.15 months and 17.21 months, respectively, with the Masquelet group demonstrating better functional outcomes [26]. For cases without soft tissue defects, our study showed a treatment success rate of 92.7% (51/55) in the single microporous titanium prosthesis implantation group, with complete weight-bearing achieved on average after 5.0 ± 0.7 months. Pain was significantly relieved at 3 months postoperatively and continued to improve until the last follow-up. This may be attributed to the protective role of complete soft tissue coverage on the prosthesis, preventing microbial colonization and mechanical stress concentration. For cases with soft tissue defects, despite more complex bone and soft tissue defects and reliance on microsurgical techniques for free flap coverage, a treatment success rate of 84.0% (21/25) was still achieved, which is consistent with previously reported success rates (82.3–96.5%) [27, 28]. Postoperative pain and lower limb function continued to improve at 3 months and beyond, with full weight-bearing achieved at 5.8 ± 1.1 months. The core advantage of free flap combined reconstruction for infected bone defects with soft tissue loss lies in the vascular support provided by the free flap, which may further influence bone healing outcomes. Given the fundamental differences in baseline disease severity and soft tissue involvement between patients treated with single prosthesis implantation and those requiring combined free flap reconstruction, these subgroups were analyzed as distinct cohorts representing different tiers of reconstructive complexity rather than being directly compared for treatment superiority.
Personalized free flap
The results of this study demonstrate certain advantages over traditional treatment methods, such as the Masquelet technique. Chen et al. [16] reported in a previous clinical study that the combination of 3D-printed microporous titanium implantation and the Masquelet technique for treating infected bone defects caused by osteomyelitis achieved a treatment success rate of 76.9% (10/13). They then preliminarily explored the efficacy of local pedicled flaps combined with 3D-printed microporous titanium implantation for treating tibial infected bone defects, with a treatment success rate of less than 60% (53.8%, 7/13 cases) [29]. Notably, the incidence of flap-related complications in that study was 30.8%, which may have been due to poor blood supply and excessive tension at the flap margins. In contrast, we did not observe any cases of free flap transplantation failure or related complications. The second-stage prosthesis implantation surgery was performed on average 4.8 ± 1.4 months after the first-stage free flap transplantation surgery. Innovatively, we used a personalized free flap (free anterolateral thigh flap) for repairing complex and large soft tissue defects, while also expanding the bone defect area from lower limb to limb-wide infected bone defects. By implementing precise infection control strategies (vancomycin-loaded bone cement release + pathogen-guided antibiotic therapy), we further enhanced the therapeutic efficacy, and the study preliminarily verified the feasibility of staged treatment (first-stage infection control combined with flap repair of soft tissue defects, second-stage mechanical reconstruction) for complex infected bone defects.
Although the anterolateral thigh flap was the preferred option in the present series, alternative free flaps may be indicated depending on the characteristics of the defect and patient-related factors. The latissimus dorsi flap provides a large volume of well-vascularized tissue and is suitable for extensive soft tissue defects [30]. The radial forearm flap offers thin and pliable coverage for smaller defects requiring contour precision [31]. The gracilis flap may be considered for moderate-sized defects when a shorter operative time and limited donor-site morbidity are desired [32]. In selected cases, a free fibular flap can simultaneously address segmental bone loss and soft tissue defects, although its use may be limited in the setting of infection or compromised recipient vessels [33]. Therefore, free flap selection should be individualized based on defect size, location, infection status, and reconstructive goals.
Diabetes and recurrent infections
Regarding postoperative complications, the overall complication rate was 10% (8/80), with recurrent infection (7.5%) and prosthesis and screw mechanical fractures (2.5%) being the most common. Among them, two diabetic patients with extensive dorsal foot soft tissue defects accompanied by large metatarsal bone defects both experienced recurrent infections postoperatively, and one diabetic patient had a recurrent tibial infection. Univariate logistic regression analysis showed that a history of diabetes was significantly associated with a higher risk of any complications and recurrent infection (p < 0.05), which drew our attention to diabetic foot osteomyelitis. Previous studies have shown that in diabetic patients, the significant changes in ischemia and neuropathy are primarily in the foot, which greatly increases the risk of foot bone infection [34, 35]. In response, our experience suggests that preoperative strict control of HbA1c (≤ 7.5%) and serum albumin ≥ 30 g/L should be prioritized. After microporous titanium implantation, we extended the antibiotic regimen to 8 weeks (instead of the usual 2 weeks) and used dynamic follow-up with infection markers to monitor recurrent infections. For the 3 cases of recurrent infection in diabetic patients, the medical team conducted detailed discussions and analyses, discovering that patients had not received standardized foot care after discharge, which may have contributed to the infection recurrence. Additionally, all three patients had varying degrees of peripheral vascular disease, which posed a challenge to flap survival and the growth environment. Therefore, we recommend that before surgical treatment of diabetic osteomyelitis patients, classification according to guidelines (high risk, low risk, or moderate risk), such as the DFU prevention and management guidelines published by the International Working Group on the Diabetic Foot (IWGDF) [36], should be conducted to facilitate targeted, stratified treatment.
Diabetes is known to impair immune function, microcirculation, and wound healing, which may contribute to persistent or recurrent infection [37]. In our clinical practice, diabetes was not considered a contraindication to microporous titanium implantation or free flap reconstruction; however, these patients were managed as a high-risk subgroup. Management strategies included strict preoperative glycemic control, optimization of nutritional and metabolic status, thorough and staged debridement when necessary, and close postoperative surveillance for early signs of infection recurrence [38, 39]. Multidisciplinary collaboration with endocrinologists and infected disease specialists was routinely employed. These measures may help mitigate infection-related risks in diabetic patients, although careful patient selection and individualized treatment planning remain essential. Moreover, Metaoy et al. [40] found that local use of antibiotic-loaded implants can increase the eradication rate of infection in diabetic foot osteomyelitis and may further reduce amputation and mortality rates. Another meta-analysis showed that diabetic foot osteomyelitis patients treated with local antibiotic delivery systems had significantly higher healing rates compared to the control group [41]. In this regard, developing a local antibiotic delivery system on the surface of microporous titanium or modifying it for controlled drug release could be an effective strategy for treating diabetic foot infected bone defects.
Nevertheless, the retrospective design of this study inevitably introduces the risk of selection bias and limits the ability to draw causal inferences. In contrast, a prospective study design would enable predefined inclusion criteria, standardized data collection, and uniform follow-up protocols, thereby improving data completeness and internal validity. Future prospective studies or registries are therefore warranted to further validate the clinical effectiveness and safety of 3D-printed microporous titanium prostheses in the management of infected bone defects. Additionally, from a clinical applicability perspective, several practical factors merit consideration, including cost, operative duration, and prosthesis manufacturing time. Patient-specific 3D-printed titanium prostheses generally involve higher upfront costs and require a manufacturing period for design and printing [42, 43]. However, these factors may be balanced by potential clinical advantages, such as reduced need for staged reconstruction, earlier weight-bearing, and avoidance of prolonged external fixation in selected cases. Operative duration is primarily influenced by the extent of bone and soft tissue defects and the need for combined free flap reconstruction, rather than by prosthesis implantation alone. Future studies incorporating standardized cost-effectiveness and workflow analyses are needed to further define the role of this technique in routine clinical practice.
Limitations
This study has several limitations: (1) The retrospective design may introduce recall bias, and the lack of a control group (such as comparisons with traditional Masquelet or Ilizarov technique) may lead to selection bias. Future studies should include prospective randomized controlled trials to verify long-term efficacy while expanding the sample size; (2) The cases in this study are still concentrated in the early to mid-term follow-up, lacking long-term follow-up data beyond 10 years, which makes it difficult to assess prosthesis wear and the risk of late loosening; (3) A limitation of this study is the absence of a validated upper-extremity functional outcome measure, such as the DASH or QuickDASH questionnaire. This was primarily due to the very small number of upper-extremity cases in the combined free flap group (n = 3), which would have rendered meaningful statistical analysis underpowered and potentially misleading. Future prospective studies with larger, multi-center cohorts are needed to allow balanced anatomical representation and comprehensive limb-specific functional evaluation (4). Risk factor exploration was based on univariate logistic regression only. Given the small number of events, multivariable modeling was not performed to avoid overfitting. Future studies with larger event numbers should apply multivariable regression to better control for confounding. Despite these limitations, this study represents the largest cohort of patients to date who underwent 3D-printed microporous titanium implantation or combined free flap repair and reconstruction for infected bone defects of the limbs, with or without soft tissue defects. The average follow-up of 40.8 months provides preliminary evidence for the feasibility and universality of personalized customization and staged treatment.
In conclusion, 3D-printed microporous titanium prostheses (either alone or combined with free flaps) provide a reliable staged solution for limb infected bone defects. Throughout the follow-up period (≥ 3 months), both the single microporous titanium group and the free flap combined group maintained continuous improvements in pain relief and lower limb function. However, larger-sample and longer-term randomized controlled trials are still required in the future to validate the feasibility and safety of this surgical approach.
Supplementary Information
Acknowledgements
Not applicable.
Authors’ contributions
Xiangwen Shi, Yipeng Wu, and Xingbo Cai: Writing-original draft & Conceptualization. Teng Wang, Shaoquan Pu and, Jian Shi: Writing-original draft, Supervision, Data curation. Xinyu Fan and Xi Yang: Writing-original draft, Resources, Methodology. Wei Lin and Xiangwen Shi: Investigation, Methodology. Yongqing Xu: Writing-review & editing, Supervision, Project administration, Funding acquisition, Conceptualization.
Funding
This study was funded by Yunnan Traumatology and Orthopedics Clinical Medical Center (Grant No. 2024YNLCYXZX0187; 2024YNLCYXZX0182); Yunnan Orthopedics and Sports Rehabilitation Clinical Medicine Research Center; National Key Research and Development Program of China (Grant No. 2022YFC2405704); Basic research project of Science and Technology Department of Yunnan Province (Grant No. 202301AC070621), and Scientific Research Fund Project Department of Education of Yunnan Province (Grant No. 2024Y251).
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
920th Hospital of Joint Logistics Support Force Committee on Ethics approved this study and consented to participate (2019-018-02). The study was performed in accordance with the Declaration of Helsinki.
Consent for publication
Not Applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.