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In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm–2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant’s inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.
Treatment of large bone defects is one of the great challenges in contemporary orthopedic and traumatic surgery. Grafts are necessary to support bone healing. A well-established allograft is demineralized bone matrix (DBM) prepared from donated human bone tissue. In this study, a fibrous demineralized bone matrix (f-DBM) with a high surface-to-volume ratio has been analyzed for toxicity and immunogenicity. f-DBM was transplanted to a 5-mm, plate-stabilized, femoral critical-size-bone-defect in Sprague-Dawley (SD)-rats. Healthy animals were used as controls. After two months histology, hematological analyses, immunogenicity as well as serum biochemistry were performed. Evaluation of free radical release and hematological and biochemical analyses showed no significant differences between the control group and recipients of f-DBM. Histologically, there was no evidence of damage to liver and kidney and good bone healing was observed in the f-DBM group. Reactivity against human HLA class I and class II antigens was detected with mostly low fluorescence values both in the serum of untreated and treated animals, reflecting rather a background reaction. Taken together, these results provide evidence for no systemic toxicity and the first proof of no basic immunogenic reaction to bone allograft and no sensitization of the recipient.
Background: The treatment of severely injured patients, especially in older age, is complex, and based on strict guidelines. Methods: We conducted a retrospective study by analyzing our internal registry for mortality risk factors in deceased trauma patients. All patients that were admitted to the trauma bay of our level-1-trauma center from 2014 to 2018, and that died during the in-hospital treatment, were included. The aim of this study was to carry out a quality assurance concerning the initial care of severely injured patients. Results: In the 5-year period, 135 trauma patients died. The median (IQR) age was 69 (38–83) years, 71% were male, and the median (IQR) Injury Severity Score (ISS) was 25 (17–34) points. Overall, 41% of the patients suffered from severe traumatic brain injuries (TBI) (AIShead ≥ 4 points). For 12.7%, therapy was finally limited owing to an existing patient’s decree; in 64.9% with an uncertain prognosis, a ‘therapia minima’ was established in consensus with the relatives. Conclusion: Although the mortality rate was primarily related to the severity of the injury, a significant number of deaths were not exclusively due to medical reasons, but also to a self-determined limitation of therapy for severely injured geriatric patients. The conscientious documentation concerning the will of the patient is increasingly important in supporting medical decisions.
The design of novel biomaterials should directly influence the host-immune system and steer it towards high biocompatibility. To date, new implants/materials have been tested for biocompatibility in vitro in cell cultures and in vivo in animal models. The current methods do not reflect reality (cell cultures) or are very time-consuming and deliver results only after weeks (animal model). In this proof-of-concept study, the suitability of a Whole Blood Stimulation Assay (WBSA) in combination with a Protein Profiler Array (PPA), as a readily available and cost-effective screening tool, was investigated. Three different biomaterials based on poly(lactic-co-glycolic acid (PLGA), calcium sulphate/-carbonate (CS) and poly(methyl methacrylate) (PMMA) were exposed to native whole blood from three volunteers and subsequently screened with a PPA. Individual reproducible protein profiles could be detected for all three materials after 24 h of incubation. The most intense reaction resulted from the use of PLGA, followed by CS. If even marginal differences in implants can be reflected in protein profiles, the combination of WBSA and PPA could serve as an early biocompatibility screening tool in the development of novel biomaterials. This may also lead to a reduction in costs and the amount of animal testing required.
The Masquelet technique is used to treat large bone defects; it is a two-stage procedure based on an induced membrane. To improve the induced membrane process, demineralized bone matrix in granular (GDBM) and fibrous form (f-DBM) was tested with and without bone marrow mononuclear cells (BMC) as filling of the membrane against the gold standard filling with syngeneic cancellous bone (SCB). A total of 65 male Sprague–Dawley rats obtained a 5 mm femoral defect. These defects were treated with the induced membrane technique and filled with SCB, GDBM, or f-DBM, with or without BMC. After a healing period of eight weeks, the femurs were harvested and submitted for histological, radiological, and biomechanical analyses. The fracture load in the defect zone was lower compared to SCB in all groups. However, histological analysis showed comparable new bone formation, bone mineral density, and cartilage proportions and vascularization. The results suggest that f-DBM in combination with BMC and the induced membrane technique cannot reproduce the very good results of this material in large, non-membrane coated bone defects, nevertheless it supports the maturation of new bone tissue locally. It can be concluded that BMC should be applied in lower doses and inflammatory cells should be removed from the cell preparation before implantation.