Reconstruction of Large Skeletal Defects: Current Clinical Therapeutic Strategies and Future Directions Using 3D Printing

Abstract

The healing of bone fractures is a well-orchestrated physiological process involving multiple cell types and signaling molecules interacting at the fracture site to replace and repair bone tissue without scar formation. However, when the lesion is too large, normal healing is compromised. These so-called non-union bone fractures, mostly arising due to trauma, tumor resection or disease, represent a major therapeutic challenge for orthopedic and reconstructive surgeons. In this review, we firstly present the current commonly employed surgical strategies comprising auto-, allo-, and xenograft transplantations, as well as synthetic biomaterials. Further to this, we discuss the multiple factors influencing the effectiveness of the reconstructive therapy. One essential parameter is adequate vascularization that ensures the vitality of the bone grafts thereby supporting the regeneration process, however deficient vascularization presents a frequently encountered problem in current management strategies. To address this challenge, vascularized bone grafts, including free or pedicled fibula flaps, or in situ approaches using the Masquelet induced membrane, or the patient's body as a bioreactor, comprise feasible alternatives. Finally, we highlight future directions and novel strategies such as 3D printing and bioprinting which could overcome some of the current challenges in the field of bone defect reconstruction, with the benefit of fabricating personalized and vascularized scaffolds.

Keywords: bone regeneration; large bone defects; three-dimensional printing; tissue engineering; vascularization.

FIGURE 1

Current biological bone reconstruction techniques. Bone defects arising due to the resection of tumors or non-union fractures can be treated with the various methods indicated, with the benefits (+) and disadvantages (−) of each technique outlined.

FIGURE 2

Fibula free vascularized flap. The anatomy including the tibia, fibula and major vessels is indicated. The surgical steps comprising the fibula flap, the gold standard clinical technique for large bone defect reconstruction, is demonstrated. Step 1 illustrates the flap dissection to obtain the bone flap with its vascular pedicle. Step 2 represents the bone flap with its vascular pedicle ready to be transplanted to the bone defect.

FIGURE 3

Workflow involved in customizable bone construct fabrication. (1) CT scans of the patient’s bone are acquired. (2) Computer aided software enables the processing of CT images in order to (3) 3D print personalized scaffolds for (4) bone defect reconstruction. The lower panel illustrates a real large bone defect reconstruction in a sheep metatarsal bone model.