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Abstract The development of synthetic bone substitutes that equal or exceed the efficacy of autologous graft remains challenging. In this study, a rat calvarial defect model was used as a reference to investigate the influence of composition and architecture of 3D-printed cement, with or without bioactives, on tissue regeneration. Printable cement pastes were formulated by combining hyaluronic acid and cement precursors. Cementitious scaffolds were printed with 3 different patterns. After 7 weeks of implantation with or without bone marrow, multiparametric qualitative and quantitative assessments were performed using µCT, SEM, and histology. None of the set-up strategies was as efficient as autologous cancellous bone graft to repair calvarial defects. Nonetheless, the presence of scaffold improved the skull vault closure, particularly when the scaffold was soaked in total bone marrow before implantation. No significant effect of scaffold macro-architecture was observed on tissue mineralization. Magnesium phosphate-based scaffolds (MgP) seemed to induce higher bone formation than their calcium-phosphate-based counterparts. They also displayed a quicker biodegradation and sparse remaining material was found after 7 weeks of implantation. Although further improvements are required to reach clinical settings, this study demonstrated the potential of organo-mineral cements for bone regeneration and highlighted the peculiar properties of MgP-based cements.

Silicon waveguides are a promising candidate for integrated nonlinear optics applications. Nonlinear coefficients of Silicon on Insulator (SOI) waveguides have been previously measured using techniques such as Z-scan, D-scan, Four Wave Mixing (FWM) and Self-phase modulation. However, they have several drawbacks such as they operate at high power or are cumbersome to setup and require multiple measurements to determine all the coefficients. In this work, we develop a direct and single measurement technique to characterize the nonlinear processes in SOI waveguides. This is achieved by employing a heterodyne interferometric technique to accurately measure minute nonlinear response. The measured nonlinear amplitude and phase shifts are fit to extract third-order nonlinear coefficients of Two-photon absorption, Kerr nonlinear index, Free carrier absorption and Free carrier dispersion. The obtained coefficients for SOI waveguides are close to that found in literature measured using the above-mentioned techniques. The advantages of this method include easy interpretation of the output signal and relatively low power of operation. It is especially advantageous for studying materials such as Phase Change Materials (PCM) in which phase changes occur dynamically. This aspect is quite promising for characterizing emerging materials for integrated photonics applications.

Introduction: Recent microsurgical reconstruction techniques benefit from the use of skin and perforator flaps that spare the donor sites. Studies on these skin flaps in rat models are numerous but there is currently no reference regarding the position of the perforators, their caliber, and the length of the vascular pedicles., Methods: We performed an anatomical study on 10 Wistar rats and 140 vessels: cranial epigastric (CE), superficial inferior epigastric (SIE), lateral thoracic (LT), posterior thigh (PT), deep iliac circumflex (DCI) and posterior intercostal (PIC) vessels. The evaluation criteria were the external caliber, the length of the pedicle, and the position of the vessels reported on the skin surface., Results: Data from the six perforator vascular pedicles are reported, with figures illustrating the orthonormal reference frame, the representation of the vessel's position, the cloud of points corresponding to the various measurements, and the average representation of the collected data. The analysis of the literature does not find similar studies; the different vascular pedicles are discussed as well as the limitations of our study: evaluation of cadaver specimen, presence of the very mobile panniculus carnosus, other perforator vessels not evaluated as well as the precise definition of perforating vessels., Conclusions: Our work describes the vascular calibers, pedicle lengths, and location of birth and arrival at the skin of the perforator vessels PT, DCI, PIC, LT, SIE, and CE in rat animal models. This work, without an equivalent in the literature, lays the foundation for future studies about flap perfusion, microsurgery, and super microsurgery learning., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical proof of concept for biomaterial-induced luminal sprouting of large-diameter vessels. In this study, we investigated if sprouting was a general response to surgical injury or placement of an inorganic construct around the vessel. Cylindrical biocement scaffolds of differing chemistries were placed around the femoral vein. A contrast agent was used to visualize vessel ingrowth into the scaffolds. Cell populations in the scaffold were mapped using immunohistochemistry. Calcium phosphate scaffolds induced 2.7-3 times greater volume of blood vessels than calcium sulphate or magnesium phosphate scaffolds. Macrophage and vSMC populations were identified that changed spatially and temporally within the scaffold during implantation. NLRP3 inflammasome activation peaked at weeks 2 and 4 and then declined; however, IL-1β expression was sustained over the course of the experiment. IL-8, a promoter of angiogenesis, was also detected, and together, these responses suggest a role of sterile inflammation. Unexpectedly, the effect was distinct from an injury response as a result of surgical placement and also was not simply a foreign body reaction as a result of placing a rigid bioceramic next to a vein, since, while the materials tested had similar microstructures, only the calcium phosphates tested elicited an angiogenic response. This finding then reveals a potential path towards a new strategy for creating better pro-regenerative biomaterials.

The reconstruction of massive segmental mandibular bone defects (SMDs) remains challenging even today; the current gold standard in human clinics being vascularized bone transplantation (VBT). As alternative to this onerous approach, bone tissue engineering strategies have been widely investigated. However, they displayed limited clinical success, particularly in failing to address the essential problem of quick vascularization of the implant. Although routinely used in clinics, the insertion of intrinsic vascularization in bioengineered constructs for the rapid formation of a feeding angiosome remains uncommon. In a clinically relevant model (sheep), a custom calcium phosphate-based bioceramic soaked with autologous bone marrow and perfused by an arteriovenous loop was tested to regenerate a massive SMD and was compared to VBT (clinical standard). Animals did not support well the VBT treatment, and the study was aborted 2 weeks after surgery due to ethical and animal welfare considerations. SMD regeneration was successful with the custom vascularized bone construct. Implants were well osseointegrated and vascularized after only 3 months of implantation and totally entrapped in lamellar bone after 12 months; a healthy yellow bone marrow filled the remaining space. STATEMENT OF SIGNIFICANCE: Regenerative medicine struggles with the generation of large functional bone volume. Among them segmental mandibular defects are particularly challenging to restore. The standard of care, based on bone free flaps, still displays ethical and technical drawbacks (e.g., donor site morbidity). Modern engineering technologies (e.g., 3D printing, digital chain) were combined to relevant surgical techniques to provide a pre-clinical proof of concept, investigating for the benefits of such a strategy in bone-related regenerative field. Results proved that a synthetic-biologics-free approach is able to regenerate a critical size segmental mandibular defect of 15 cm 3 in a relevant preclinical model, mimicking real life scenarii of segmental mandibular defect, with a full physiological regeneration of the defect after 12 months., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

The development of instruments combining multiple characterization and imaging tools drove huge advances in material science, engineering, biology, and other related fields. Notably, the coupling of SEM with micro-Raman spectrometry (μRaman) provides the means for the correlation between structural and physicochemical properties at the surface, while dual focused ion beam (FIB)-scanning electron microscopes (SEMs) operating under cryogenic conditions (cryo-FIB-SEM) allow for the analysis of the ultrastructure of materials in situ and in their native environment. In cryo-FIB-SEM, rapid and efficient methods for assessing vitrification conditions in situ are required for the accurate investigation of the original structure of hydrated samples. This work reports for the first time the use of a cryo-FIB-SEM-μRaman instrument to efficiently assess the accuracy of cryo-fixation methods. Analyses were performed on plunge-freezed highly hydrated calcium phosphate cement (CPC) and a gelatin composite. By making a trench of a defined thickness with FIB, μRaman analyses were carried out at a specific depth within the frozen material. Results show that the μRaman signal is sensitive to the changes in the molecular structures of the aqueous phase and can be used to examine the depth of vitreous ice in frozen samples. The method presented in this work provides a reliable way to avoid imaging artifacts in cryo-FIB-SEM that are related to cryo-fixation and therefore constitutes great interest in the study of vitreous materials exhibiting high water content, regardless of the sample preparation method (i.e., by HPF, plunge freezing, and so on).

Massive segmental bone defects (SBD) are mostly treated by removing the fibula and transplanting it complete with blood supply. While revolutionary 50 years ago, this remains the standard treatment. This review considers different strategies to repair SBD and emerging potential replacements for this highly invasive procedure. Prior to the technical breakthrough of microsurgery, researchers in the 1960s and 1970s had begun to make considerable progress in developing non autologous routes to repairing SBD. While the breaktthrough of vascularised bone transplantation solved the immediate problem of a lack of reliable repair strategies, much of their prior work is still relevant today. We challenge the assumption that mimicry is necessary or likely to be successful and instead point to the utility of quite crude (from a materials technology perspective), approaches. Together there are quite compelling indications that the body can regenerate entire bone segments with few or no exogenous factors. This is important, as there is a limit to how expensive a bone repair can be and still be widely available to all patients since cost restraints within healthcare systems are not likely to diminish in the near future. STATEMENT OF SIGNIFICANCE: This review is significant because it is a multidisciplinary view of several surgeons and scientists as to what is driving improvement in segmental bone defect repair, why many approaches to date have not succeeded and why some quite basic approaches can be as effective as they are. While there are many reviews of the literature of grafting and bone repair the relative lack of substantial improvement and slow rate of progress in clinical translation is often overlooked and we seek to challenge the reader to consider the issue more broadly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)