Critical bone defect of lower weight-bearing extremity is a challenge1,2. Traditional treatment options, such as bone grafting1,2, Ilizarov external fixator,3 and Masquelet technique4, have limitations such as long treatment cycle, pin loose or track infection, and requirement for additional bone grafts5,6. To better solve these dilemmas, some researchers reconstructed the defects by implanting three-dimensional (3D)-printed scaffolds with loading massive bone grafts7,8,9; however, the source of autogenous bone graft (ABG) limited their application. Our previous reports showed that 3D porous scaffold could achieve new bone regeneration and stable mechanical support for treating spinal defects without bone grafts10,11. Besides, the animal experiments12,13 showed that new bone could grow around and inside the scaffold. The transverse microcomputed tomography (CT) scan and histological analysis further confirmed the new ingrown bone after 12 weeks. The absence of additional bong grafting did not prohibit new bone regeneration, and the good rhBMP2-loading capacity of the 3D-printed Ti6Al4V scaffold was also displayed.
Ipsilateral critical fractures of femur and tibia are rare and intractable. We designed an innovative treatment strategy, namely, using 3D-porous scaffold to reconstruct the defects without additional ABG. This was the first report dealing with this special condition. Our case illustrated its novel application with a successful short-term result.
The patient was informed that data concerning the case would be submitted for publication, and she provided consent.
Case Report
A 42-year-old woman was accidentally hit by a motorcycle 3 years ago and experienced open comminuted fractures on the ipsilateral distal femur, tibia. and fibula. No neurovascular injury existed. The patient underwent debridement and open reduction with internal fixation for femoral and fibular fractures and external fixator treatment for tibial fracture initially. No definite infection was diagnosed during the whole treatment cycle.
The physical examination revealed soft-tissue atrophy on her right lower limb, without redness, ulceration, and sinus (Fig. 1-A). The flexion and extension ranges of the knee were 85° and 5°, and the dorsiflexion and plantar flexion range of ankle were 20° and 30°, respectively. She could walk only with the help of a crutch or jump by left leg because of her personal subjective feeling of leg instability and pain, and fear to bear weight. As displayed by x-ray and CT (Figs. 1-B and 1-C), the femoral and tibial fractures partially healed with an intact lateral plate on the right distal femur and good alignment, but with a 15.5-cm section of distal diaphysis with only a small amount of bone spanning the gap. She had a healed fibular shaft fracture with the remaining plate and a tibial shaft in good alignment with an 8.5-cm section, with only a lateral cortex of healing bone spanning the gap. We did not find infection or abscess, as detected on CT and magnetic resonance imaging (Figs. 1-C and 1-D). Combined with further negative results of laboratory test, microbial culture, and histopathologic examination, this patient was diagnosed with post-traumatic nonunion and critical bone defect of the ipsilateral femur and tibia.
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Fig. 1: Fig. 1-A Shows the scar, soft-tissue atrophy, and pigmentation on the skin of right leg. Figs. 1-B and 1-C display the critical bone defect of the femur and tibia. Fig. 1-D is the preoperative coronal magnetic resonance imaging showing no obvious infection or abscess. Fig. 1-E is the full-length x-ray in the standing position, indicating that the right lower extremity is shorter than the left 1.
The patient and her family were fully informed about the bone lengthening and Masquelet technique, and they chose the novel strategy based on the customized 3D-printed technique. We designed a personalized therapeutic regimen mainly including the following 2 stages:
- The first stage involved the debridement of fibrous tissue and small amount of bone in the tibia and femur until cortical bleeding (namely, the paprika sign). The removed bone mainly included the dissociative sequestrum and the marginal bone lacking vascular supply. Some suspicious tissues were assigned for further bacterial culture. After radical debridement, 2 critical bone defects were left in the femur (15.5 cm) and tibia (8.5 cm) with an irregular anatomical shape. The polymethyl methacrylate (PMMA) cement spacers were used to fill defects with the femur stabilized by the initial plate and tibia through external fixation (Fig. 2-A). Vacuum sealing drainage was used to cover the wound in the early stage. Once the culture and biopsy results were confirmed to be negative, the wounds were closed with the spacers remained. Induced membrane could gradually develop around PMMA spacers, and we designed customized scaffolds for both femur and tibia during the waiting interval.
Fig. 2: Fig. 2-A shows that the critical defects of both femur and tibia were filled with bone cement spacer, with the tibia being fixed by a temporary external fixator. Figs. 2-B and 2-C show the design process of the patient-specific three-dimensional-printed scaffold via digital virtual technology (5 times magnification); the opposite natural limb was used to help scaffold design as a template based on the mirror principle. Figs. 2-D and 2-E display the anteroposterior and lateral x-rays at 7 days after the scaffolds were implanted and fixed.
The scaffolds were designed with the aid of special anatomic landmarks around the defects and natural skeletal structures from the contralateral side (mirror principle) shown on bilateral high-precision CT images (Figs. 2-B and 2-C). The preexisting bone bridging around the defects was also taken into consideration. The scaffold comprised Ti6Al4V and was fabricated via selective laser melting (EBM Arcam Q10) directed by the computer aided design data in Weigao Medical Group. We obtained scaffolds with the elastic modulus of 1,200 ± 48 MPa and a weaker stress-shielding effect14. The scaffolds had a pore size of 625 ± 70 μm, high interconnectivity, and a porosity of 70% for better biomechanical support and bone regeneration15. A central hole was chiseled in the central part of the scaffolds to accommodate subsequent intramedullary (IM) nail insertion. The distal end of femoral prosthesis was close to knee surface (3.7 cm), and the distal residual bone quality was poor. Hence, a lateral plate was designed for screw fixation. After fabrication and rinse, the scaffolds were sterilized and packed for the surgical procedure.
- The second stage followed an interval of approximately 8 weeks. The critical defects of both femur and tibia were repaired simultaneously using 3D-printed scaffolds and IM nail fixation (Figs. 2-D and 2-E). According to the postoperative x-ray in the standing position, the length of the right leg was a little shorter than that of the right (0.7 cm), but we decided to accept this shortening.
During the postoperative rehabilitation, immediate unrestricted joint exercises and gradual weight bearing were directed by professional therapists. The patient could walk slowly without the help of a crutch after 1 month. The Harris score and the hospital for special surgery score reached 93 and 83, respectively, and her right leg could bear full weight of the body without any restriction at 12 months postoperatively. The flexion and extension range of knee joint were 98° and 0°, and the dorsiflexion and plantar flexion range of ankle joint were 25° and 35°, respectively. After 26 months, the x-ray displayed no instrumental failure and new bone regeneration (as shown by a red arrow in Fig. 3-B). The satisfaction score was 96 points in a 100% system at the final follow-up. No signs of infection, scaffold loosening or breakage, and deformity were found during the follow-up.
Fig. 3: Figs. 3-A and 3-B display the anteroposterior and lateral X-rays at 26 months after surgery; no instrumental failure and loosen were observed. Fig. 3-C shows the normal flexion function of knee and ankle at 12 months after surgery. Fig. 3-D shows the weight bearing function of right leg has returned to normal completely.
Discussion
Simple bone grafting was difficult to repair defects at a height more than 6 cm because of gradual bone resorption8,16,17. Some shorter defects could also be successfully treated with distraction osteogenesis or the Masquelet technique, but these methods were associated with various serious complications. In the present case, the length of both defects was more than 8 cm, which made the treatment by traditional methods difficult. Customized 3D-printed porous scaffolds showed the potential ability to complete this formidable task, although no study ever reported such an attempt.
A patient-specific 3D scaffold could accurately match the defect and dramatically shorten the treatment cycle. In addition, stable mechanical support and axis biomechanical conduction could guarantee early weight bearing. Based on our previous findings10-13, we disregarded additional bone grafting and further increased the feasibility of this innovative strategy. Besides, the scaffold was inserted inside the induced membrane cabin, which promoted the new bone regeneration18,19.
The design of the scaffold was also worthy of enough attention. In this study, we successfully obtained the suitable elastic modulus (1,200 ± 48 MPa) with appropriate porous architecture (pore size = [625±70] μm, porosity = 70%). The follow-up x-rays displayed the gradual regeneration of new bone on the scaffold surface.
The IM nail was conductive to make the stress in the defect area more dispersed and avoid stress concentration. The force could evenly transmit to the residual bone in metaphysis when prosthesis contacted well with the residual bone. We assumed that the axial micromotion at the interface region between the scaffold and the host bone might stimulate the new bone ingrowth, and osseointegration might be achieved20,21. According to the 26-month follow-up, the patient walked without the help of a crutch for more than 18 months. No implant loosening or breakage was detected.
Indeed, the accurate mechanical survival of the prosthetic implant is unknown. The prosthesis, similar to all inert materials, is subject to fatigue failure and potential loosening over time. The implants may eventually fail and require revision. Besides, the application of a medullary nail and a titanium scaffold may exert influence on the local blood supply and new bone regeneration, which needs further relevant researches.
In summary, customized 3D-printed implantation without additional bone grafting helped to reconstruct ipsilateral critical femoral and tibial bone defects simultaneously. The short-term results indicated that the patient regained early weight bearing and ambulatory function, which was maintained for more than 2 years. However, the entire bony healing and osseointegration have not been observed, and more uncertainties such as scaffold loosening or breakage and internal fixation failure may happen in the future. We welcome interested readers to contact the authors for more details, and we hope more researchers share their experience about managing ipsilateral critical femoral and tibial bone defects.
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