In situ production of pre-vascularized synthetic bone grafts for regenerating critical-sized defects in rabbits.

Reconstructing large bone defects caused by severe trauma or resection of tumors remains a challenge for surgeons. A fibula free flap and its vascularized bed can be transplanted to the reconstruction site to achieve healing. However, this technique adds morbidity, and requires microsurgery and sculpting of the bone tissue to adapt the graft to both the vasculature and the anatomy of the defect. The aim of the current study was to evaluate an alternative approach consisting of the in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a critical-sized bone defect. 3D printed chambers containing biphasic calcium phosphate (BCP) granules, perfused by a local vascular pedicle, with or without the addition of stromal vascular fraction (SVF), were subcutaneously implanted into New Zealand White female rabbits. SVF was prepared extemporaneously from autologous adipose tissue, the vascular pedicle was isolated from the inguinal site, while BCP granules alone served as a control group. After 8 weeks, the constructs containing a vascular pedicle exhibited abundant neovascularization with blood vessels sprouting from the pedicle, leading to significantly increased vascularization compared to BCP controls. Pre-vascularized synthetic bone grafts were then transplanted into 15 mm critical-sized segmental ulnar defects for a further 8 weeks. Micro-CT and decalcified histology revealed that pre-vascularization of synthetic bone grafts led to enhanced bone regeneration. This pre-clinical study demonstrates the feasibility and efficacy of the in situ production of pre-vascularized synthetic bone grafts for regenerating large bone defects, thereby addressing an important clinical need. STATEMENT OF SIGNIFICANCE: The current gold standard in large bone defect regeneration is vascularized fibula grafting. An alternative approach consisting of in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a bone defect is presented here. 3D printed chambers were filled with biphasic calcium phosphate granules, supplemented with autologous stromal vascular fraction and an axial vascular pedicle and subcutaneously implanted in inguinal sites. These pre-vascularized synthetic grafts were then transplanted into critical-sized segmental ulnar defects. Micro-CT and decalcified histology revealed that the pre-vascularized synthetic bone grafts led to higher bone regeneration than non-vascularized constructs. An alternative to vascularized fibula grafting is provided and may address an important clinical need for large bone defect reconstruction.

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

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 post-implantation. 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.

Poor prognosis for infectious complications of surgery for ankle and hindfoot fracture and dislocation. A 34-case series.

INTRODUCTION: Ankle and hindfoot fractures are associated with high rates of complications, and of infection in particular, for which rates of 1% to 48% are reported. HYPOTHESIS: Treatment of bone and joint infection (BJI) secondary to surgery for ankle or hindfoot fracture is at high risk of failure. We analyzed results of treatment of BJI in this context. MATERIAL AND METHODS: 33 patients (34 cases) were treated for ankle or hindfoot BJI between 2010 and 2015. Cure was defined by absence of fistula and of local or general inflammatory signs and by normal C-reactive protein level, at a minimum 2 years' follow-up. Fusion without infection was counted as success; recurrent infection and amputation were counted as failure. Mean age at trauma was 52 years (range, 16-85 years). Median time to diagnosis of BJI was 44 days (range, 2-830 days). RESULTS: Mean follow-up was 20 months (range, 3-59 months). Twenty-two patients were cured (65%). Seven cases required joint fusion (21%). The failure rate was 15%, including 5 transtibial amputations. Skin cover flap was required for 15 patients (44%), at a median 33 days (range, 0-167 days). DISCUSSION: Despite its retrospective design and small numbers, the present study confirmed the poor prognosis of BJI following surgery for ankle and/or hindfoot fracture. Patients need to be informed of this. TYPE OF STUDY AND LEVEL OF EVIDENCE: IV, retrospective observational.