Reconstruction Of Bone Defects Research Articles

Induced membrane technique in the treatment of infected tibial bone defect: A retrospective study.

To investigate the effect of the induced membrane technique (IMT) in the treatment of infected tibial bone defect. IMT is a 2-stage procedure dedicated to reconstruction of bone defects of the limbs. Treating injuries of the tibia characterized by segmental bone loss, severe damage to the soft tissue, and a conjoining infection is a challenge using IMT. A retrospective study was performed among the patients treated using IMT for infected tibial bone defect between 2017 and 2020. The complications were recorded, and the bone defect union and the functional results were evaluated by Paley method. All patients were followed up for at least 1 year. We included 12 patients (11 males) with a mean age of 44.5 years (range 19-65). The mean length of bone defect was 26.7 mm (range 10-60). The mean interval between the stage 1 and the stage 2 of the procedure was 11.8 weeks (range 4-32). At a mean follow-up of 18.08 months (range 12-32), bone union was achieved in all cases in a mean time of 8 months (range 5-16) without infection recurrence, where 1 patient received additional bone grafting. The joint function recovered well for the patients and the rate of functionally excellent and good results was 9/12. IMT in the treatment of infected tibial bone defect offers the advantages of simple operation, use of a smaller amount of autograft bone, and low recurrence rate of infection.

Is liquid nitrogen recycled bone and vascular fibula combination the biological reconstruction of choice in lower extremity long bone tumor-related defects?

Combination techniques, which encompass the combined use of vascularized bone grafts with massive allografts or autografts (recycled bone grafts), are especially important in the biological reconstruction of tumor-related lower extremity long bone defects. Liquid nitrogen recycled bone (frozen autograft) and free vascular fibula graft (FVFG) combination, which was coined as the "frozen hotdog (FH)" method by the authors, has not been as widely used nor its outcomes reported for significantly sized patient groups. This study aims to provide an answer to whether FH is a safe and effective reconstructive tool for limb salvage in malignant tumors of the lower extremity regarding radiological, functional, and oncological outcomes. Sixty-six (male/female: 33/33) patients, who underwent FH reconstruction for tumor-related massive defects of lower extremity long bones between 2006 and 2020, were retrospectively analyzed. The mean age was 15.8 (3.8-46.7) years. The most common tumor localizations were distal femur (42.4%) and proximal tibia (21.2%) while classic osteosarcoma and Ewing's sarcoma were the most common pathologies (60.6% and 22.7%, respectively). Mean resection and FVFG lengths were 160 (90-320) mm and 192 (125-350) mm, respectively. The mean follow-up was 73.9 (24-192) months. The mean MSTS score was 25.4 (15-30) and the mean ISOLS radiographic score was 22.6 (13-24). Mean time to full weight bearing without any assistive devices was 15.4 (6-40) months and the median time was 12 months. MSTS score negatively correlated with resected segment length and vascular fibula length (p < 0.001; p = 0.006). Although full contact apposition of the FH segment correlated with earlier full weight bearing compared to partial apposition (mean 13.7 vs. 17.9 months) (p = 0.042), the quality of reduction did not affect the ISOLS radiographic score at LFU. Overall limb survival rate was 96.3% at 5 and 10 years while FH survival rate was 91.0% and 88.1% at 5 and 10 years. Local recurrence-free survival rates were 88.8% and 85.9%, and overall survival was 89.9% and 86.1% at 5 and 10 years, respectively. Limb length discrepancy was the most common complication with 34 (51.5%) patients while shell nonunion was seen in 21 (31.8%) patients and graft fracture in 6 (9.1%). The "FH" method is a safe, effective, and extremely cost-efficient reconstructive tool for tumor-related lower extremity long bone defects. Patient compliance to protracted weight-bearing, ensuring the vitality of the FVFG, and achieving an oncologically safe resection are key factors for a successful outcome.

Distal Humeral Replacement in Patients with Primary Bone Sarcoma: The Functional Outcome and Return to Sports

Distal humeral replacement (DHR) is a limb-salvage option for the endoprosthetic reconstruction of bone defects following the resection of a primary bone sarcoma. As primary bone sarcomas are only occasionally located around the distal humerus, there is a paucity of information regarding postoperative function, and patients’ resumption of sporting activities. With advances in diagnostics and in surgical and oncological treatment leading to an increased patient life expectancy and higher quality of life, patients’ functional outcome and return to sports activities are of increasing interest. Between 1997 and 2021, a total of 24 patients underwent DHR with a single-design modular implant at a tertiary sarcoma center. A total of 14 patients who died of their disease were excluded, leaving a study cohort of 10 patients, with a median age of 30 years on the day of surgery (IQR 20–37). At the last follow-up, after a median of 230 months (IQR 165–262), the median MSTS was 19 (IQR 13–24), the median TESS was 79 (IQR 66–87), the median SEV was 38% (IQR 24–53), the median TS was 6 (IQR 4–7), and the median WAS was 3 (IQR 1–8). Among the variables of gender, surgery on the dominant extremity, intraoperative nerve resection, extra-articular tumor resection, chemotherapy, radiotherapy, and revision surgeries, none were associated with a better/lower functional outcome score or return to sports activities. However, a higher level of sports performance prior to diagnosis (WAS &gt; 10) was associated with a higher level of sports performance postoperatively (p = 0.044).

Treatment outcome of the Masquelet technique in 195 infected bone defects–A single-center, retrospective case series

BackgroundThe Masquelet technique is a surgical procedure for the reconstruction of bone defects. During the first step, an osteosynthetically stabilized defect is filled with a cement spacer. The spacer induces a foreign body membrane, called a Masquelet membrane. In a follow-up procedure, the spacer is replaced by a bone graft, which ossifies in the subsequent phase. Material and MethodsA total of 171 patients with 195 septic bone defects on the extremities that had been treated with the Masquelet procedure at the BG Klinikum in Hamburg, Germany, from 2011 to 2021 were retrospectively analysed, comparing patients who reached full weight and load bearing on the affected extremity to those who failed to do so. Defect size and configuration, microbiological results and treatment methods as well as comorbidities and epidemiologic data were analysed for factors influencing the treatment outcome. ResultsIn all, 113[66%] of the patients were male, and 58[34%] were female, with an age distribution of 52 +/-16 years. Out of 171 patients, 24 patients had two defects. The number of patients that reached full weight bearing was 152[89%], the follow-up period was 2 +/-1 years (median +/- SD). Full weight bearing capability was negatively by the defect size as defects >62 mm tended to be less likely to reach full weight bearing than smaller defects. A secondary stabilization with an internal stabilization was applied in 58[34%] of all patients and positively influenced the attainment of full weight and load bearing. DiscussionWith 171 patients and 195 septic bone defects treated at a single centre with the Masquelet Technique, this study represents a comparably large cohort. Demographics, defect characteristics and treatment outcomes did not differ from those of other cohorts described in the literature. Defects larger than 62 mm showed lower chances to reach full weight bearing and can be defined as "critical defect size" for the Masquelet technique based on our data.

The Role of Radiological Vascular Assessment and Computer-Aided Planning in The Outcome of Free Vascularized Fibula Flap for Bone Defects Reconstruction

The Role of Radiological Vascular Assessment and Computer-Aided Planning in The Outcome of Free Vascularized Fibula Flap for Bone Defects Reconstruction

Outcome of Limb Salvaging Procedure for Bone Tumor Using Liquid Nitrogen Technique: A Case Series of 21 Patients

Abstract Introduction and importance: Autologous bone graft treated with liquid nitrogen is an option for biological reconstruction of bone defects in patients receiving tumor resection. This is the first report in Hong Kong on the outcome of this biological reconstruction in terms of functional outcome, local recurrence rate, and prognosis. Case presentation: From 2015 to 2021, 21 patients with bone tumor resection and reconstruction using liquid nitrogen treated autologous bone graft were recruited. The medical records and radiological images were retrieved for retrospective review. After delivery of the specimen, all the soft tissue of the excised bone was removed at the back table before cryotherapy. The auto graft was immersed in liquid nitrogen for 20 minutes, and thawed at room temperature for 10 minutes. After that the autograft was immersed in distilled water for 15 minutes before being incorporated into the reconstruction. All of them were followed up for at least one year post-operation. Clinical discussion: The mean union time was 13.3 months (from 4 to 31 months). The mean Musculoskeletal Tumor Society (MSTS) score was 22.6 (from 12 to 30). The mean follow up time was 38.2 months (from 12 to 64 months). There were two local soft tissue recurrences and one local recurrence from host bone. Conclusion: Autologous bone graft treated with liquid nitrogen is a safe option for biological reconstruction of bone defects after tumor resection. It provides satisfactory outcomes with low local recurrence rate, as well as comparable complications with other reconstruction methods.

Orthopaedic Advances: Use of Three-Dimensional Metallic Implants for Reconstruction of Critical Bone Defects After Trauma.

Multiple successful strategies exist for the management of critical-sized bone defects. Depending on the location and etiology of an osseous defect, there are nuances that must be considered by the treating surgeon. The induced membrane technique and various modifications of the Ilizarov method (bone transport by distraction osteogenesis) have been the most common methods for biologic reconstruction. Despite the versatility and high union rates reported, they may not be practical for every patient. The rapid expansion of three-dimensional printing of medical devices has led to an increase in their use within orthopaedic surgery, specifically in the definitive treatment of critical bone defects. This article proposes indications and contraindications for implementation of this technology and reviews the available clinical evidence on the use of custom nonresorbable implants for the treatment of traumatic bone loss. Clinical cases are presented to illustrate the scenarios in which this approach is viable.

The antibiotic bead pouch - a useful technique for temporary soft tissue coverage, infection prevention and therapy in trauma surgery.

Soft tissue defects resulting from trauma and musculoskeletal infections can complicate surgical treatment. Appropriate temporary coverage of these defects is essential to achieve the best outcomes for necessary plastic soft tissue defect reconstruction. The antibiotic bead pouch technique is a reasonable surgical approach for managing temporary soft tissue defects following adequate surgical debridement. This technique involves the use of small diameter antibiotic-loaded bone cement beads to fill the dead space created by debridement. By applying antibiotics to the bone cement and covering the beads with an artificial skin graft, high local dosages of antibiotics can be achieved, resulting in the creation of a sterile wound that offers the best starting position for soft tissue and bone defect reconstruction. This narrative review describes the rationale for using this technique, including its advantages and disadvantages, as well as pearls and pitfalls associated with its use in daily practice. In addition, the article provides a comprehensive overview of the literature that has been published since the technique was introduced in surgical practice.

Injectable Platelet-Rich Fibrin in Contact with Bone Substitutes, Porous Zirconia, or Laser-Textured Implant Surfaces: A Detailed Morphological Analysis

AbstractThe aim of the present study was to perform a detailed morphological analysis of an injectable platelet rich fibrin after combination with two different particulate hydroxyapatite-based granules, a porous zirconia block, and laser-textured zirconia or titanium surfaces. Blood samples were harvested from three participants to prepare the flowable injectable PRF in contact or not with particulate hydroxyapatite (Hap), bone mineral granules (DBBM), porous zirconia blocks, laser-textured titanium or zirconia surfaces. Optical and scanning electron microscopy (SEM) were used to evaluate the fibrin network density, fibrin fibers’ diameter, blood cells, and the interaction of PRF with the biomaterials. Histomorphometry of the flowable PRF was also performed using the hematoxylin–eosin staining protocol. Specimens were independently evaluated by two blinded and well-trained researchers in histomorphometry and microscopy. Particulate Hap and DBBM shown different morphological aspects by SEM analyses since DBBM revealed macro- and micro-scale pores while Hap revealed a dense structure. Hydroxyapatite and DBBM granules were entirely embedded by the fibrin-network in the presence of leukocytes and blood platelets. The zirconia porous structured was filled with PRF and its components. Also, the laser-structured zirconia or implant surfaces were entirely coated with the PRF fibrin network embedding leukocytes and blood platelets. Laser-textured titanium surfaces revealed macro- and micro-scale irregularities that increase the surface area and retention of the injectable PRF. Histomorphometric analyses revealed complementary details on the distribution of lymphocytes, red blood cells, and fibrin associated with platelet aggregation. The flowing and viscosity of an injectable platelet rich fibrin provided an agglomeration of synthetic or xenogeneic particulate bone substitutes and the coating of porous zirconia and textured implant surfaces as inspected by scanning electron microscopy. A cross-linked 3D-fibrin network was noticed involving the particulate bone substitutes and clogging the spaces into porous blocks as well as at macro-/micro-scale valleys on laser-textured implant surfaces. On the reconstruction of larger bone defects, platelet rich fibrin should be mixed with inorganic bone substitutes and implant surfaces to speed up the early events of the bone ingrowth. In addition, the particulate bioactive ceramics, porous zirconia, and textured implant surfaces provide the mechanical stability of the bone tissues and the 3D-fibrin network for further stimulation of osteogenic cells leading to an enhanced bone healing.

A quantitative CT analysis of fibula inlayed in a massive allograft for femoral diaphysis reconstruction

IntroductionIn diaphyseal reconstructions for bone tumor resection, massive bone allografts (MBA) are historically regarded as the gold standard. However, these are not without complications, and they present an elevated risk of infection, nonunion and structural failure that increases over time as the graft remains largely avascular. To counteract this disadvantage, a combination of allograft with a vascularized fibula has been proposed. The aim of our study was to objectively review the results of combined vascularized fibula-allograft constructs compared to plain allograft reconstruction for bone defects in tumor patients and to assess fibular vitality predictive factors from imaging studies. Materials and methodsOur data was retrospectively reviewed for patients with femoral diaphysis reconstructions in the past ten years. Ten patients (six males and four females) with a mean average follow-up time of 43.80 months (range 20–83, SD 18.17) with combined graft (Group A) were included in the study. As a control group 11 patients (six males and five females) with a mean average follow-up of 56.91 months (range 7–118, SD 41.33) with a simple allograft reconstruction were analyzed (Group B). Demographic and surgical data, adjuvant therapy as well as complications were analyzed in both groups. Both groups were assessed with plain radiographs for bony fusion at the osteotomy sites. Patients in “Group A” had consecutive CT scans at 6 months and then annually to check for potential bone stock and bone density changes. We analyzed total bone density as well as incremental changes in three different areas of the reconstruction. This was done at two defined levels for each patient. Only patients with at least two consecutive CT scans were included in the study. ResultsThere were no statistical differences between the groups in terms of demographics, diagnosis or adjuvant therapy (p = 1.0). The mean average surgical time (599.44 vs 229.09) and mean average blood loss (1855.56 ml vs. 804.55 ml) were significantly higher in the combined graft group A (p < 0.001 and p = 0.01, respectively). The mean average length of resection (19.95 cm vs. 15.50 cm) was higher in the combined graft group (p = 0.04). The risk for non-union and infectious complication was higher in the allograft group, however, the difference was not significant (p = 0.09 and p = 0.66, respectively). The mean average time to union at junction sites was 4.71 months (range 2.5–6.0, SD 1.19) for cases of successful fibula transfer, 19.50 months (range 5.5–29.5, SD 12.49) for the three cases where we presumed the fibula was not viable and 18.85 months (range 9–60, SD 11.99) for the allograft group. The difference in healing time was statistically significant (p = 0.009). There were four cases of non-union in the allograft group.Seven out of ten patients in Group A exhibited incremental changes in all CT scan measured values. This difference was statistically significant already at 18 months from the index surgery (p = 0.008). The patients with a non-viable fibula had a smaller increase in the percentage of total bone density area measured in the CT scan compared to those patients with a successful fibula transfer (4.33, SD 2.52 vs. 52.29, SD 22.74, p = 0.008). The average bone density incremental increase in-between the fibula and allograft was different among patients with an unsuccessful fibula transfer (32.22, SD 10.41) and the ones with a viable fibula (288.00, SD123.74, p = 0.009). Bony bridges were observed in six cases of viable fibula and in none of the tree presumably dead fibulas (p = 0.03). The mean average MSTS score was higher for the subgroup of successful fibular transfer (26.7/30, SD 2.87) when compared to the group of non-viable fibular graft (17.00/30, SD 6.08) and this was also statistically significant (p = 0–007). ConclusionA viable fibula enhances incorporation of the allograft and decreases the risk for both structural failure as well as infectious complications. Viable fibula also contributes to better functional status of the recipient. Consecutive CT scans proved to be a reliable method for assessing fibular vitality. When no measurable changes are present at 18-month follow-up, we can declare the transfer unsuccessful with a good amount of certainty. These reconstructions behave as simple allograft reconstructions with analogue risk factors. The presence of either axial bridges between the fibula and allograft or newly formed bone on the inner surface of the allograft is indicative of a successful fibular transfer. The success rate of fibular transfer in our study was only 70% and skeletally mature and taller patients seem to be at increased risk for failure. The longer surgical times and donor site morbidity therefore warrant stricter indications for this procedure.

Limited internal fixation combined with a hinged external fixator in treatment of peri-elbow bone infection

To evaluate the effectiveness of limited internal fixation combined with a hinged external fixator in the treatment of peri-elbow bone infection. The clinical data of 19 patients with peri-elbow bone infection treated with limited internal fixation combined with a hinged external fixator between May 2018 and May 2021 were retrospectively analyzed. There were 15 males and 4 females with an average age of 44.6 years (range, 28-61 years). There were 13 cases of distal humerus fractures and 6 cases of proximal ulna fractures. All the 19 cases were infected after internal fixation of fracture, and 2 cases were complicated with radial nerve injury. According to Cierny-Mader anatomical classification, 11 cases were type Ⅱ, 6 cases were type Ⅲ, and 2 cases were type Ⅳ. The duration of bone infection was 1-3 years. After primary debridement, the bone defect was (3.04±0.28) cm, and the antibiotic bone cement was implanted into the defect area, and the external fixator was installed; 3 cases were repaired with latissimus dorsi myocutaneous flap, and 2 cases were repaired with lateral brachial fascial flap. Bone defects repair and reconstruction were performed after 6-8 weeks of infection control. The wound healing was observed, and white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) were reexamined regularly after operation to evaluate the infection control. X-ray films of the affected limb were taken regularly after operation to observe the bone healing in the defect area. At last follow-up, the flexion and extension range of motion and the total range of motion of the elbow joint were observed and recorded, and compared with those before operation, and the function of the elbow joint was evaluated by Mayo score. All patients were followed up 12-34 months (mean, 26.2 months). The wounds healed in 5 cases after skin flap repair. Two cases of recurrent infection were effectively controlled by debridement again and replacement of antibiotic bone cement. The infection control rate was 89.47% (17/19) in the first stage. Two patients with radial nerve injury had poor muscle strength of the affected limb, and the muscle strength of the affected limb recovered from grade Ⅲ to about grade Ⅳ after rehabilitation exercise. During the follow-up period, there was no complication such as incision ulceration, exudation, bone nonunion, infection recurrence, or infection in the bone harvesting area. Bone healing time ranged from 16 to 37 weeks, with an average of 24.2 weeks. WBC, ESR, CRP, PCT, and elbow flexion, extension, and total range of motions significantly improved at last follow-up ( P<0.05). According to Mayo elbow scoring system, the results were excellent in 14 cases, good in 3 cases, and fair in 2 cases, and the excellent and good rate was 89.47%. Limited internal fixation combined with a hinged external fixator in the treatment of the peri-elbow bone infection can effectively control infection and restore the function of the elbow joint.

Molecules Inducing Dental Stem Cells Differentiation and Bone Regeneration: State of the Art.

Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables, and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 10 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. The reconstruction of bone defects, in fact, is still a challenge and therefore more research is needed; the articles reviewed are meant to identify compounds useful to stimulate d-DSC proliferation and osteogenic differentiation. We only consider the results of the research which is encouraging, assuming that the mentioned compounds are of some importance for bone regeneration.

Customed 3D-printed Polyetheretherketone (PEEK) Implant for Secondary Salvage Reconstruction of Mandibular Defects: Case Report and Literature Review.

Given the insufficient height of single-barrel fibula and inadequate bone volume of double-barrel vascularized fibula in mandibular reconstruction, it is a better choice to combine the upper full-thickness vascularized fibula with the lower half-thickness nonvascularized fibula. However, the nonvascularized fibula may fail due to complications, affecting the facial shape and occlusal function. Polyetheretherketone is a thermoplastic polymer used for bone defect reconstruction due to its good mechanical properties and biocompatibility. This case report mainly presents a secondary salvage reconstruction of the mandible by using customed 3-dimensional-printing polyetheretherketone, which restored the continuity and symmetry of the mandible, improved the patient's facial shape, and restored functional occlusion through dental implants. After a 28-month follow-up, no complications occurred, and the patient was satisfied with the final restoration.

Comparative Evaluation of the Effect of Two Platelet Concentrates (a-PRF and L-PRF) on the Cellular Activity of Pre-osteoblastic MG-63 Cell Line: An in vitro Study.

Currently, the reconstruction of bone defects with new platelet concentrates is considered a significant challenge in periodontics. This study aimed to evaluate advanced- platelet rich fibrin (A-PRF) and leukocyte- and platelet rich fibrin's (L-PRF) effects on the proliferation and differentiation of MG-63 cells. In this in vitro study, blood samples of five healthy non-smoking volunteers were collected and immediately centrifuged according to the two protocols of Choukroun and Ghanaati, without adding any anticoagulants, to prepare L-PRF and A-PRF. After freezing the clots for one hour, they were crushed and centrifuged once more. After culturing MG-63 cells, the effects of 20%, 10%, 1%, and 0.5% concentrations of A-PRF and L-PRF extracts on cell proliferation and mineralization were evaluated by methyl thiazolyl tetrazolium (MTT) assay and Alizarin Red staining, respectively. Generally, survival and proliferation in the L-PRF group at both time intervals were higher than the A-PRF group and increased with increasing the extract concentration. However, in the A-PRF group, there were no significant differences between the different concentrations, and only the number of cells increased over time. After three days, in the study on mineralization, nodule formation was observed only in the positive control group (osteogenic). In seven days, mineralized nodules were formed in all groups with different concentrations of A-PRF, but not in any of the L-PRF groups. According to the results, L-PRF increased proliferation, and A-PRF exerted a positive effect on the differentiation of MG-63 cells.

Development and characterizations of graded porous titanium scaffolds via selective laser melting for orthopedics applications

To improve the treatment effect of bone defect repair, titanium scaffolds having graded structures with porosities of 78.8%, 70.8%, 62.6%, and 54.4% (denoted as P1, P2, P3, and P4, respectively) were designed and fabricated by selective laser melting. The manufacturability, microstructure, mechanical properties, and permeability were investigated theoretically and experimentally. Simulation results showed that the maximum von Mises stress and permeability were in the range of 569.1–1469.0 MPa and (21.7–54.6)×10−9 m2 respectively. Thereinto, P3 and P4 exhibited lower maximum von Mises stress, meaning a higher strength. The microstructure of fabricated scaffolds with P3 and P4 consisted of martensitic α′ phase. The yield strength and elastic modulus were 185.3-250.8 MPa and 6.1-9.7 GPa, respectively. Compared with the scaffold with P3, the scaffold with P4 exhibited higher yield strength and a more matched elastic modulus to cortical bone, and its permeability (18.6×10−9 m2) was within the range of permeability of human bone. Comprehensively, the scaffold with P4 is a promising candidate for bone defect reconstructions.

Fabrication of a composite 3D-printed titanium alloy combined with controlled in situ drug release to prevent osteosarcoma recurrence

Osteosarcoma is a malignant bone tumor occurring in adolescents. Surgery combined with adjuvant or neoadjuvant chemotherapy is the standard treatment. However, systemic chemotherapy is associated with serious side effects and a high risk of postoperative tumor recurrence, leading to a high amputation rate and mortality in cancer patients. Implant materials that can simultaneously repair large bone defects and prevent osteosarcoma recurrence are in urgent need. Herein, an intelligent system comprising 3D-printed titanium scaffold (TS) and pH-responsive PEGylated paclitaxel prodrugs was fabricated for bone defect reconstruction and recurrence prevention following osteosarcoma surgery. The drug-loaded implants exhibited excellent stability and biocompatibility for supporting the activity of bone stem cells under normal body fluid conditions and the rapid release of drugs in response to faintly acidic environments. An in vitro study demonstrated that five human osteosarcoma cell lines could be efficiently eradicated by paclitaxel released in an acidic microenvironment. Using mice models, we demonstrated that the drug-loaded TS can enable a pH-responsive treatment of postoperative tumors and effectively prevent osteosarcoma recurrence. Therefore, local implantation of this composite scaffold may be a promising topical therapeutic method to prevent osteosarcoma recurrence.

High Risk for Persistent Peri-Prosthetic Infection and Amputation in Mega-Prosthesis Reconstruction.

A peri-prosthetic joint infection is a feared complication after mega-prosthesis reconstruction of large bone defects. The current study investigates how patients operated with a mega-prosthesis due to sarcoma, metastasis, or trauma, are affected by a deep infection focusing on re-operations, risk for persistent infection, arthrodesis, or subsequent amputation. Time to infection, causative bacterial strains, mode of treatment and length of hospital stay are also reported. A total of 114 patients with 116 prostheses were evaluated, a median of 7.6 years (range 3.8-13.7) after surgery, of which 35 (30%) were re-operated due to a peri-prosthetic infection. Of the infected patients, the prosthesis was still in place in 51%, 37% were amputated, and 9% had an arthrodesis. The infection was persistent in 26% of the infected patients at follow-up. The mean total length of hospital stay was 68 (median 60) days and the mean number of reoperations was 8.9 (median 6.0). The mean length of antibiotic treatment was 340 days (median 183). Coagulase-negative staphylococci and Staphylococcus aureus were the most frequent bacterial agents isolated in deep cultures. No MRSA- or ESBL-producing Enterobacterales were found but vancomycin-resistant Enterococcus faecium was isolated in one patient. In summary, there is a high risk for peri-prosthetic infection in mega-prostheses, resulting in persistent infection or amputation relatively often.

Overexpression of fibroblast growth factor receptor 2 in bone marrow mesenchymal stem cells enhances osteogenesis and promotes critical cranial bone defect regeneration.

Background: Reconstruction of cranial bone defects is one of the most challenging problems in reconstructive surgery, and several biological tissue engineering methods have been used to promote bone repair, such as genetic engineering of bone marrow mesenchymal stem cells (BMSCs). Fibroblast growth factor receptor 2 (Fgfr2) is an important regulator of bone construction and can be used as a potential gene editing site. However, its role in the osteogenesis process of BMSCs remains unclear. This article clarifies the function of Fgfr2 in BMSCs and explores the role of Fgfr2-overexpressed BMSCs carried by light-induced porous hydrogel (GelMA) in the repair of cranial bone defects. Methods: Lenti-virus was used to overexpress Fgfr2 in BMSCs, and cell counting kit-8, transwell, and flow cytometry assays were conducted to investigate the proliferation, migration, and characteristics. After 0, 3, 7, and 10 days of osteogenic or chondrogenic induction, the changes in osteogenic and chondrogenic ability were detected by real-time PCR, western blot, alkaline phosphatase staining, alizarin Red staining, and alcian blue staining. To investigate the viability of BMSCs carried by GelMA, calcein and propyl iodide staining were carried out as well. Finally, a critical cranial bone defect model was established in 6-week-old male mice and micro-computerized tomography, masson staining, and immunohistochemistry of OCN were conducted to test the bone regeneration properties of implanting Fgfr2-overexpressed BMSCs with GelMA in cranial bone defects over 6 weeks. Results: Overexpression of Fgfr2 in BMSCs significantly promoted cell proliferation and migration and increased the percentage of CD200+CD105+ cells. After osteogenic and chondrogenic induction, Fgfr2 overexpression enhanced both osteogenic and chondrogenic ability. Furthermore, in cranial bone defect regeneration, BMSCs carried by light-induced GelMA showed favorable biocompatibility, and Fgfr2-overexpressed BMSCs induced superior cranial bone regeneration compared to a normal BMSCs group and an untreated blank group. Conclusion: In vitro, Fgfr2 enhanced the proliferation, migration, and stemness of BMSCs and promoted osteogenesis and chondrogenesis after parallel induction. In vivo, BMSCs with Fgfr2 overexpression carried by GelMA showed favorable performance in treating critical cranial bone defects. This study clarifies the multiple functions of Fgfr2 in BMSCs and provides a new method for future tissue engineering.

Research progress on autologous vascularized graft bone implant repair for maxillofacial bone defect

Maxillofacial bone defect can seriously affect the patient's appearance, mastication, deglutition and speech function. At present, autologous bone grafting combined with implant repair is an effective method for reconstruction of maxillofacial bone defects. Due to the differences in density, nutrition, immunity and other aspects of bone graft at different donor sites, there may be a potential impact on implant repair. In this paper, the biological characteristics of vascularized autologous bone used in maxillofacial bone defect repair were reviewed, and the risk factors of implantation on the bone graft were discussed. It provides support for clinicians in the selection of bone graft donor site and the design of prosthesis.

Vascularization of a Bone Organoid Using Dental Pulp Stem Cells.

Bone organoids offer a novel path for the reconstruction and repair of bone defects. We previously fabricated scaffold-free bone organoids using cell constructs comprising only bone marrow-derived mesenchymal stem cells (BMSCs). However, the cells in the millimetre-scale constructs were likely to undergo necrosis because of difficult oxygen diffusion and nutrient delivery. Dental pulp stem cells (DPSCs) are capable of differentiating into vascular endothelial lineages and have great vasculogenic potential under endothelial induction. Therefore, we hypothesized that DPSCs can serve as a vascular source to improve the survival of the BMSCs within the bone organoid. In this study, the DPSCs had greater sprouting ability, and the proangiogenic marker expressions were significantly greater than those of BMSCs. DPSCs were incorporated into the BMSC constructs at various ratios (5%-20%), and their internal structures and vasculogenic and osteogenic characteristics were investigated after endothelial differentiation. As a result, the DPSCs are differentiated into the CD31-positive endothelial lineage in the cell constructs. The incorporation of DPSCs significantly suppressed cell necrosis and improved the viability of the cell constructs. In addition, lumen-like structures were visualized by fluorescently labelled nanoparticles in the DPSC-incorporated cell constructs. The vascularized BMSC constructs were successfully fabricated using the vasculogenic ability of the DPSCs. Next, osteogenic induction was initiated in the vascularized BMSC/DPSC constructs. Compared with only BMSCs, constructs with DPSCs had increased mineralized deposition and a hollow structure. Overall, this study demonstrated that vascularized scaffold-free bone organoids were successfully fabricated by incorporating DPSCs into BMSC constructs, and the biomimetic biomaterial is promising for bone regenerative medicine and drug development.