Regeneration of segmental defects in metatarsus of sheep with vascularized and customized 3D-printed calcium phosphate scaffolds

Abstract

Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months postimplantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. the presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds. Bone is a dynamic tissue that possesses the intrinsic capacity to heal within 6-8 weeks after immobilization of a fracture. However, there are some conditions in which bone regeneration is delayed, compromised or beyond the physiological healing potential 1,2. Notably, the successful repair of large bone defects caused by trauma, tumor resection or disease remains a clinical challenge for orthopedic and plastic surgeons and often requires additional treatments. Autologous bone grafting is still considered the gold standard treatment due to its osteoconductive, osteoinductive and osteogenic properties. This procedure necessitates harvesting the patient's own bone and subsequently transplanting it to the defect site. Bone can be taken from several areas e.g., iliac crest or fibula, depending on the severity and amount needed for reconstruction of the defect. Nevertheless, the amount of

Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus

“…ch/). www.nature.com/scientificreports/ calcium phosphate scaffold with an included vascular pedicle promoted greater bone formation than the scaffold alone at 3 months after implantation in a 3.5 cm critical size segmental metatarsal defect 10 . For the treatment of long bone nonunion, rhBMP-2 has yielded even better results than rhBMP-7 with regards to both overall rates of healing as well as the average time to union 26 .…”

“…prevascularized bone scaffold for single-phase surgical treatment 10,11 . Using the patient's body as a bioreactor is an alternative strategy to prevascularize bone grafts for reconstruction of large bone defects 12,13 .…”

Personalized medicine for reconstruction of critical-size bone defects – a translational approach with customizable vascularized bone tissue

“…The femoral vascular bundle was directly implanted into the scaffold in the defect site leading to a higher degree of bone and vessel formation compared to defects without vascularization 22 . Likewise, Vidal et al performed a pilot study in sheep metacarpal bone defect, implanting a vascular pedicle from the defect surroundings directly into a 3D-printed bone substitute for supporting vascularization and bone formation 23 . Recently, we were able to demonstrate the successful implementation of in situ tissue engineering in two patients by using a tissue-engineered construct and a vascular axis from the defect surroundings 24 .…”

Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect

“…The progress in rapid prototyping has expanded the potential for patient specific implants with the possibility of designing and manufacturing biomaterials of intricate geometry in a fast and affordable way [17][18][19][20]. Cements can be used in robocasting, a technique where the cement is ejected through a nozzle and 3D printed.…”