A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

Current cranial repair techniques combine the use of autologous bone grafts and biomaterials. In addition to their association with harvesting morbidity, autografts are often limited by insufficient quantity of bone stock. Biomaterials lead to better outcomes, but their effectiveness is often compromised by the unpredictable lack of integration and structural failure. Bone tissue engineering offers the promising alternative of generating constructs composed of instructive biomaterials including cells or cell-secreted products, which could enhance the outcome of reconstructive treatments. This review focuses on cell-based approaches with potential to regenerate calvarial bone defects, including human studies and preclinical research. Further, we discuss strategies to deliver extracellular matrix, conditioned media and extracellular vesicles derived from cell cultures. Recent advances in 3D printing and bioprinting techniques that appear to be promising for cranial reconstruction are also discussed. Finally, we review cell-based gene therapy approaches, covering both unregulated and regulated gene switches that can create spatiotemporal patterns of transgenic therapeutic molecules. In summary, this review provides an overview of the current developments in cell-based strategies with potential to enhance the surgical armamentarium for regenerating cranial vault defects.

Application of decellularized bone matrix as a bioscaffold in bone tissue engineering

Autologous bone grafts are commonly used as the gold standard to repair and regenerate diseased bones. However, they are strongly associated with postoperative complications, especially at the donor site, and increased surgical costs. In an effort to overcome these limitations, tissue engineering (TE) has been proposed as an alternative to promote bone repair. The successful outcome of tissue engineering depends on the microstructure and composition of the materials used as scaffold. Decellularized bone matrix-based biomaterials have been applied as bioscaffolds in bone tissue engineering. These biomaterials play an important role in providing the mechanical and physical microenvironment needed by cells to proliferate and survive. Decellularized extracellular matrix (dECM) can be used as a powder, hydrogel and electrospun scaffolds. These bioscaffolds mimic the native microenvironment due to their structure similar to the original tissue. The aim of this review is to highlight the bone decellularization techniques. Herein we discuss: (1) bone structure; (2) properties of an ideal scaffold; (3) the potential of decellularized bone as bioscaffolds; (4) terminal sterilization of decellularized bone; (5) cell removing confirmation in decellularized tissues; and (6) post decellularization procedures. Finally, the improvement of bone formation by dECM and the immunogenicity aspect of using the decellularized bone matrix are presented, to illustrate how novel dECM-based materials can be used as bioscaffold in tissue engineering. A comprehensive understanding of tissue engineering may allow for better incorporation of therapeutic approaches in bone defects allowing for bone repair and regeneration.

Long-term follow-up of applying autologous bone grafts for reconstructing tympanomastoid defects in functional cholesteatoma surgery

Objectives This study investigated the long-term surgical outcomes of functional cholesteatoma surgery with canal wall reconstruction using autologous bone grafts as the primary material in patients with acquired cholesteatoma. Subjects and Methods Medical charts were retrospectively reviewed for all patients admitted to one institution for surgical intervention between 2010 and 2018. We analyzed 66 patients (66 ears) who underwent functional tympanomastoidectomy involving the use of autologous bone grafts for canal wall defect reconstruction. Surgical outcomes were evaluated by comparing preoperative audiometric results with follow-up data (at least 36 months after surgery). Logistic regression analyses were performed to determine prognostic factors related to long-term hearing success. These factors included classification and stage of cholesteatoma, stapes condition, ossicular chain damage, active infection of the middle ear, state of the contralateral ear, preoperative hearing thresholds, gender, and age. Results The mean follow-up period was 49.2 months. The recidivism rate was 6% (four of 66 ears). The pure-tone average significantly improved from 50.78 ± 19.98 to 40.81 ± 21.22 dB hearing level (HL; p < 0.001). Air–bone gaps significantly improved from 26.26 ± 10.53 to 17.58 ± 8.21 dB HL (p < 0.001). In multivariate logistic regression analysis, early-stage disease (p = 0.021) and pars flaccida cholesteatoma (p = 0.036) exhibited statistically significant correlations with successful hearing preservation. Conclusion Functional cholesteatoma surgery with autologous bone grafts reconstruction is an effective approach to significantly improve hearing with low recidivism rates. Localized disease and pars flaccida cholesteatoma were two independent predictors of successful hearing preservation.

A Case Series: Non-vascularized Autologous Fibular Graft in the Treatment of Major Segmental Bone Defect after Post-traumatic at Diaphyseal Femur

BACKGROUND In the management of bony defects, autologous bone grafts can be used as the mechanical structure for reconstruction to restore aesthetics and function, Non-vascularized autologus fibular graft are often used to the treat large post traumatic defects caused by high-energy trauma with open fracture and nonunion cases for 1st and 2nd cases. Here we would like to present a 16-year-old woman and a 37-year-old man patients of major bone defect at the right femoral shaft region using 9 cm and 10 cm non-vascularized fibular autogenous grafts. OBJECTIVE The purpose of this case report was to determine the effectiveness of non-vascularized autologus fibular graft for major bone defect at the regio femoral shaft for the reconstruction of post traumatic case. MATERIAL AND METHODS We treat post traumatic of the major bone defect at the regio femoral shaft with 9 cm and 10 cm femoral non-vascularized autologus fibular graft and fixed by a limited contact dynamic compression plate and femoral locking plate methode by routine phisioteraphy. RESULTS The Patient have a good result with good functional outcome after open reduction internal fixation (ORIF) and using a non-vascularized autologus fibular graft for treating the major bone defect after post traumatic femoral shaft fracture. CONCLUSION Complete and comperhensive open reduction internal fixation (ORIF) with autologous non- vascularized fibular graft, stabilized fracture by limited contact dynamic compression plate for 1st patient and femoral locking plate for 2nd patient allowing with an early rehabilitation is an acceptable, Phisioteraphy and early mobilisation resulting better outcome for the patient, all of this are less expensive, can be accepted at the hospitals that limited facilities and health professionals for professional subspeciality and widely reproducible option to manage bone defects in open shaft femoral fractures to achieving union, preserving length and motion with no donor site morbidity, giving patients good functional outcome and radiologic result. KEYWORDS Major bone defect, non-vascularized autologus fibular graft, autologous bone grafts, femoral shaft fracture, Open Fracture, Muskuloskeletal Reconstruction, Bone Loss, Nonunion.

Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute

Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague–Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by µ-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.

Advanced backward planning with custom-milled individual allogeneic block augmentation for maxillary full-arch osteoplasty and dental implantation:a 3-year follow-up

In the case of maxillary involution, augmentation is necessary for implant-supported prosthetics. The use of bone grafts is standard; customized allogeneic bone blocks may be a predictable alternative before dental implantation. For maxillary full-arch reconstruction, this case shows a horse-shoe augmentation by four allogeneic blocks, followed by guided dental implantation and fixed prosthetics after 6 months of healing. Using allogeneic blocks is an option for full-arch maxillary augmentation and comparable with autologous bone grafts. There is no donor site comorbidity. Bone height is stable for a minimum of 3 years after loading with resorption less than 10% in vertical, buccolingual, and mesiodistal directions. Short-implants allow for the long-term stability of prosthetic fixtures. Prefabricated customized allogeneic blocks for augmentation may increase the fitting accuracy of the graft, decrease morbidity, and lower operation time in maxillary full-arch reconstruction. The percentage of resorption after 3 years is comparable to the commonly used iliac crest.

Advantages of Porcine Xenograft over Autograft in Sinus Lift: A Randomised Clinical Trial

This study aimed to compare the performance of intra-oral autologous bone grafts versus porcine xenografts in a two-step lateral window sinus lift. This split-mouth randomised controlled trial sequentially enrolled 12 patients with a 6-month follow-up. For each patient, a simultaneous randomised bilateral maxillary sinus lift was performed and filled with autologous bone from the mandible (control) or a porcine xenograft (test). A bone biopsy sample was collected during the implant placement for histological and histomorphometric analysis. CT scans were performed at the beginning and at the end of the trial to assess radiological evolution. A comparison of initial and six-month CT scans indicated statistically significant increases in bone level for both materials (7.8 ± 2.4 mm for autologous and 8.7 ± 2.2 mm for xenograft, p < 0.05), and there were no significant differences between the performance of the two materials over time (p = 0.26). The histological analysis showed various stages of the remodelling process and no cells or other signs of inflammation or infection were visible in both groups. The porcine xenografts presented similar results for the studied variables when compared to autologous bone, being a reasonable alternative for a sinus lift.

Intensive Care as an Independent Risk Factor for Infection after Reconstruction and Augmentation with Autologous Bone Grafts in Craniomaxillofacial Surgery: A Retrospective Cohort Study

Autologous bone grafts for reconstruction and augmentation are routinely used for maintaining functionality and facial aesthetics. Associated complications, however, have a significant impact on patients and health care systems. This study aims to investigate the possible risk factors associated with the occurrence of complications in order to provide evidence for the outcome of autologous bone graft reconstructive procedures. Patients from 2008 to 2018 who underwent autologous (mostly mandibular) reconstruction were included in the observational study. Clinical, pathological, and therapeutic factors were examined in univariate and multivariate analysis for significance with occurring complications. A multivariate model was used to create a prognostic model predicting the occurrence of complications. Graft complications requiring revision were exhibited by 33/128 patients. Infections were most frequent, with 4/22 patients affected by multi-resistant germs. Multivariate analysis showed radiotherapy (OR = 5.714; 95% CI: 1.839–17.752; p = 0.003), obstructive pulmonary disease (OPD) (OR = 4.329; 95% CI: 1.040–18.021; p = 0.044) and length of defect (in mm) (OR = 1.016; 95% CI: 1.004–1.028; p = 0.009) as independent risk factors associated with graft complications with high accuracy of prediction (AUC = 0.815). Intensive care (OR = 4.419; 95% CI: 1.576–12.388; p = 0.005) with a coefficient between intensive care and OPD (0.214) being low was identified as the most relevant risk factor for infection. Although intensive care is not a classic risk factor, but rather a summation of factors not reaching significance in the individual case, a stay in ICU (intensive care unit) needs to be considered for graft complications. As a clinical consequence, we recommend using the best possible hygienic measures during procedures e.g., while performing dressing and drainage changes in ICU.

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

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.