Smart Implantable Hydrogel for Large Segmental Bone Regeneration.

Large segmental bone defects often lead to nonunion and dysfunction, posing a significant challenge for clinicians. Inspired by the intrinsic bone defect repair logic of "vascularization and then osteogenesis", this study originally reports a smart implantable hydrogel (PDS-DC) with high mechanical properties, controllable scaffold degradation, and timing drug release that can proactively match different bone healing cycles to efficiently promote bone regeneration. The main scaffold of PDS-DC consists of polyacrylamide, polydopamine, and silk fibroin, which endows it with superior interfacial adhesion, structural toughness, and mechanical stiffness. In particular, the adjustment of scaffold cross-linking agent mixing ratio can effectively regulate the in vivo degradation rate of PDS-DC and intelligently satisfy the requirements of different bone defect healing cycles. Ultimately, PDS hydrogel loaded with free desferrioxamine (DFO) and CaCO3 mineralized ZIF-90 loaded bone morphogenetic protein-2 (BMP-2) to stimulate efficient angiogenesis and osteogenesis. Notably, DFO is released rapidly by free diffusion, whereas BMP-2 is released slowly by pH-dependent layer-by-layer disintegration, resulting in a significant difference in release time, thus matching the intrinsic logic of bone defect repair. In vivo and in vitro results confirm that PDS-DC can effectively realize high-quality bone generation and intelligently regulate to adapt to different demands of bone defects.

Bone transport combined with sequential nailing technique for the management of large segmental bone defects after trauma.

Background: Bone transport technique is widely used for the management of large segmental bone defects. However, several reasons may prevent its successful completion, such as poor osteogenesis, docking site nonunion, severe chronic pain and psychological problems. We used sequential nailing technique to solve these problems. The objective of this study was to analyze the clinical effects of our modified technique for the management of large segmental bone defects after trauma. Methods: Twenty-three patients using bone transport combined with sequential nailing technique in our institution from June 2011 to June 2020 were included and analyzed retrospectively. There were 15 males and eight females. The age ranged from 19 to 64 years. There were eight cases suffering from basic medical diseases. The initial injury was open in 14 patients. Seven cases encountered femoral defects and 16 for tibia. The main reasons for sequential nailing technique were docking site nonunion (nine cases), poor osteogenesis (five cases), severe chronic pain (five cases) and psychological problems (four cases). The residual bone defects after removing the external fixator, operation plans, complications and follow-up time were recorded. Bone defect healing was evaluated by Paley score. Results: The mean residual bone defects were (2.9 ± 1.9) cm. The mean time in external fixator was (9.5 ± 3.4) months. The average follow-up time was (23 ± 3) months. With respect to complications, two cases suffered from nonunion again and were treated by bone graft with augmented plate fixation. No infection recurrence was found in these cases. The excellent and good rate of bone defect healing was 91.3%. Conclusion: Bone transport combined with sequential nailing technique could shorten the external fixation time, overcome the inconvenience of the external frame to patients, eliminate chronic pain and be easy for patients to accept. Patients using this modified technique achieved high satisfaction.

Effect of different HA/ß-TCP coated 3D printed bioceramic scaffolds on repairing large bone defects in rabbits.

BACKGROUND: Treatment of large segmental bone defects is still a major clinical challenge, and bone grafting is the main method. The development of novel bone graft substitutes will help solve this problem. METHODS: Porous bioceramics hydroxyapatite (HA) scaffolds coated with different ratios of HA/ß-tricalcium phosphate (ß-TCP) were prepared by 3D printing. The scaffolds were sampled and tested in large segmental bone defect rabbit models. X-ray, micro-computed tomography (CT), hematoxylin and eosin (HE) staining, Van-Gieson staining, and type I collagen staining were performed to find the best scaffolds for large segmental bone defect treatment. RESULTS: The average length, diameter, compressive strength, and porosity of the bioceramics scaffolds were 15.05 ± 0.10 mm, 4.98 ± 0.06 mm, 11.11 ± 0.77 MPa, and 54.26 ± 5.38%, respectively. Postoperative lateral radiographs suggested the scaffold group got better bone healing and stability than the blank group. Micro-CT showed new bones grew into the scaffold from the two ends of the fracture along the scaffold and finally achieved bony union. The new bone volume around the scaffolds suggested the 3:7 HA/ß-TCP-coated bioceramic scaffolds were more favorable for the healing of large segmental bone defects. The results of HE, Van-Gieson, and type I collagen staining also suggested more new bone formation in 3:7 HA/ß-TCP-coated bioceramic scaffolds. CONCLUSION: 3:7 HA/ß-TCP-coated porous bioceramics scaffolds are more conducive to the repair of large bone defects in rabbits. The results of this study can provide some reference and theoretical support in this area.

Management of segmental defects post open distal femur fracture using a titanium cage combined with the Masquelet technique A single-centre report of 23 cases.

INTRODUCTION: The segmental bone defects post open distal femur fracture presents a reconstructive challenge, which often requires extreme solutions. The present study reviewed a new treatment strategy which used a cylindrical titanium mesh cage as an adjunct to the Masquelet technique. METHODS: We retrospectively reviewed a consecutive series of 23 patients treated for segmental bone defects post open distal femur fracture using a titanium mesh cage combined with the Masquelet technique under a 2-staged protocol in our institution from 2017 to 2021. The study group consisted of 13 men and 10 women with an average age of 44.1 years. The surgical debridement was performed with antibiotic polymethylmethacrylate (PMMA) cement spacer implanted into the bone defect combined with cement-wrapped plate stabilization, or antibiotic beads with vacuum sealing drainage (VSD) to cover the wound. The second stage of the Masquelet technique for bone defect repair began at least 4-6 weeks after the first stage, once all signs of possible infection were eliminated. After the cement spacer was removed, the definitive reconstruction was completed with exchange to a cylindrical titanium mesh cage filled with cancellous autograft within the induced membrane. The bone defect with cage was stabilized with a distal femoral Less Invasive Stabilization System (LISS). The radiological and clinical records of the enrolled patients were retrospectively analyzed. RESULTS: The mean follow-up was 38.6 months. The average number of operations before the second stage was 1.3. The mean interval between the two stages was 12.7 weeks. The average length of the defect measured 8.3 cm (ranging from 6.1 to 12.4 cm). All the defects filled with autograft within the cage achieved bony union, with a mean healing time of 8.4 months. At the latest follow-up, the mean knee extension measured 6.2° (ranging from 0° to 20°), and the mean flexion measured 101.8° (ranging from 60° to 120°). Complications included two instances of superficial stitch abscess, which eventually healed. CONCLUSIONS: The use of a titanium cage implanted into an induced membrane in a 2-staged Masquelet protocol could achieve satisfactory clinical outcomes in cases of segmental defects following open distal femur fractures.

Filling the gap: a series of 3D-printed titanium truss cages for the management of large, lower limb bone defects in a developing country setting.

INTRODUCTION: Large segmental long bone defects are notoriously difficult to manage. Treatment is resource-intensive due to the complexity, cost, and specialized skills required. Truss designs are known for their triangular shapes organized in web configurations. This allows for maximal mechanical strength, the least mass, and a lattice that can be filled with bone graft. Using a truss cage combined with contemporary internal fixation provides immediate stability for bone ingrowth and long-term potential union. The implant is designed using virtual 3D modelling of the patient's bone defect based on a CT scan. The truss cage can be used in a staged procedure combined with Masquelet's induced membrane technique. This study aims to review the outcomes of patient-specific, locally designed 3D titanium truss cages packed with cancellous autograft in treating segmental, long bone defects in the lower limb in a developing country setting. METHODS: This retrospective series reviewed cases performed at various institutions between January 2019 and March 2022. Parameters assessed included patient demographics, size and location of the defect, time to clinical and radiological union and complications. RESULTS: Nine cases were included for review, with a mean age of 36 years (range 19-52). Defects ranged from 60 to 205 mm, and eight cases were staged procedures. Eight cases used intramedullary reamings as bone graft. Contemporary intramedullary nails were used for fixation in all cases. No peri- or post-operative complications occurred. All cases progressed to functional union. CONCLUSION: 3D-printed titanium truss cages combined with bone graft appear to be an effective treatment of large bone defects in the lower limb in a developing country setting in the short term. No complications were encountered, but longer follow-up is needed before definitive recommendations can be made. LEVEL OF EVIDENCE: Level IV (retrospective case series).

3D bioprinting of in situ vascularized tissue engineered bone for repairing large segmental bone defects.

Large bone defects remain an unsolved clinical challenge because of the lack of effective vascularization in newly formed bone tissue. 3D bioprinting is a fabrication technology with the potential to create vascularized bone grafts with biological activity for repairing bone defects. In this study, vascular endothelial cells laden with thermosensitive bio-ink were bioprinted in situ on the inner surfaces of interconnected tubular channels of bone mesenchymal stem cell-laden 3D-bioprinted scaffolds. Endothelial cells exhibited a more uniform distribution and greater seeding efficiency throughout the channels. In vitro, the in situ bioprinted endothelial cells can form a vascular network through proliferation and migration. The in situ vascularized tissue-engineered bone also resulted in a coupling effect between angiogenesis and osteogenesis. Moreover, RNA sequencing analysis revealed that the expression of genes related to osteogenesis and angiogenesis is upregulated in biological processes. The in vivo 3D-bioprinted in situ vascularized scaffolds exhibited excellent performance in promoting new bone formation in rat calvarial critical-sized defect models. Consequently, in situ vascularized tissue-engineered bones constructed using 3D bioprinting technology have a potential of being used as bone grafts for repairing large bone defects, with a possible clinical application in the future.

Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants.

So far, how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic. In this study, a strategy of combining osteoinductive biphasic calcium phosphate (BCP) bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects (3.0 cm in length) in goat femur model. The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa, and total porosity of 84%. The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage, promoting the osteogenic process both guided and induced by the BCP scaffolds. At 9 months postoperatively, good integration between the implants and host bone was observed, and a large amount of newborn bones formed, accompanying with the degradation of the material. At 18 months postoperatively, almost the complete new bone substitution in the defect area was achieved. The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery. Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects. The current study could provide an effective method to treat the clinical large segmental bone defects.

Masquelet technique in post-traumatic infected femoral and tibial segmental bone defects. Union and reoperation rates with high proportions (up to 64%) of allograft in the second stage.

Introduction The aim of this study was to describe union, reoperation and failure rates after using the induced membrane (IM) technique with ≥50% allograft over autograft to treat infected femoral and tibial segmental bone defects (SBD). Materials and methods We retrospectively analyzed patients with femoral and tibial SBD treated in our center between 2012 and 2019 using ≥50% allograft over autograft during the second stage of the Masquelet technique. We analyzed the affected bone, defect size, osteosynthesis technique used, time elapsed between the first and second stage of the technique, graft proportions, union time, reoperations, and non-union rates. Results We included 21 patients (61.90% men) with a median age of 41 (range 18-68) years. The tibia was affected in 61.90% (n:13) and the femur in 38.09% (n:8) of the cases. SBD length was 4.5 (range 3.5-14) cm. The median interval between both stages of the technique was 10 (range 6-28) weeks. The proportion of allograft used was 50 % in 10 patients, 51 to 55% in 5 patients, 56 to 59% in 4 patients, and 60 to 64% in 2. The union rate was 95.23% over a median time of 7 (range 6-12) months. There were 3 (14.28%) reoperations: 2 for relapse of infection and 1 for mechanical instability. There was one failure (4.76%). One patient presented non-union and nail break. The median follow-up after the second stage of the technique was 26 (range 13-54) months. Conclusion The use of the induced membrane technique and a high proportion of allograft (up to 64%) achieved similar union and failure rates than those reported for similar series that relied on lower allograft proportions.

Urine-derived stem cells loaded onto a chitosan-optimized biphasic calcium-phosphate scaffold for repairing large segmental bone defects in rabbits.

The treatment of large segmental bone defects can be challenging for orthopedic surgeons. The development of bone tissue engineering technology, including the selection of seeding cells and the construction of scaffolds, provides a promising solution. In this study, we investigated osteogenic differentiation of human urine-derived stem cells (hUSCs, a newly identified class of stem cells), and developed a novel porous hybrid scaffold using biphasic calcium phosphate (BCP) bioceramic ornamented with chitosan sponges (CS). We combined hUSCs with a CS/BCP hybrid scaffold to construct tissue-engineered bone and evaluated whether the combination promotes bone regeneration in large segmental bone defects in rabbits. The study showed that hUSCs can differentiate into osteoblasts, and the hUSCs adhered, proliferated, and differentiated on CS/BCP hybrid scaffolds. Micro-computed tomography measurements, biomechanical detection, and histological analyses revealed that the combination of hUSCs and the CS/BCP hybrid scaffold enhanced bone regeneration more effectively compared with conventional pure BCP scaffolds, indicating that hUSCs can be used as a cell source for bone tissue engineering and that cell-scaffold-based biomimetic bone may be a promising approach to the repair of bone defects.