Svetlana a supervised segmentation classifier for Napari.

We present Svetlana (SuperVised sEgmenTation cLAssifier for NapAri), an open-source Napari plugin dedicated to the manual or automatic classification of segmentation results. A few recent software tools have made it possible to automatically segment complex 2D and 3D objects such as cells in biology with unrivaled performance. However, the subsequent analysis of the results is oftentimes inaccessible to non-specialists. The Svetlana plugin aims at going one step further, by allowing end-users to label the segmented objects and to pick, train and run arbitrary neural network classifiers. The resulting network can then be used for the quantitative analysis of biophysical phenoma. We showcase its performance through challenging problems in 2D and 3D and provide a comprehensive discussion on its strengths and limits.

Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis.

Inflammation, a crucial defense mechanism, must be rigorously regulated to prevent the onset of chronic inflammation and subsequent tissue damage. Specialized pro resolving mediators (SPMs) such as lipoxin A4 (LXA4) have demonstrated their ability to facilitate the resolution of inflammation by orchestrating a transition of M1 pro-inflammatory macrophages towards an anti-inflammatory M2 phenotype. However, the hydrophobic and chemically labile nature of LXA4 necessitates the development of a delivery system capable of preserving its integrity for clinical applications. In this study, two types of emulsion were formulated using different homogenization processes:mechanical overhead stirrer (MEB for blank Emulsion and MELX for LXA4 loaded-Emulsion) or Luer-lock syringes (SEB for blank Emulsion and SELX for LXA4 loaded-Emulsion)). Following characterization, including size and droplet morphology assessment by microscopy, the encapsulation efficiency (EE) was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). To exert control over LXA4 release, these emulsions were embedded within silanized hyaluronic acid hydrogels. A comprehensive evaluation, encompassing gel time, swelling, and degradation profiles under acidic, basic, and neutral conditions, preceded the assessment of LXA4 cumulative release using LC-MS/MS. Physicochemical results indicate that H-MELX (Mechanical overhead stirrer LXA4 Emulsion loaded-Hydrogel) exhibits superior efficiency over H-SELX (Luer-lock syringes LXA4 Emulsion loaded-Hydrogel). While both formulations stimulated pro-inflammatory cytokine secretion and promoted a pro-inflammatory macrophage phenotype, LXA4 emulsion-loaded hydrogels displayed a diminished pro-inflammatory activity compared to blank emulsion-loaded hydrogels. These findings highlight the biological efficacy of LXA4 within both systems, with H-SELX outperforming H-MELX in terms of efficiency. To the best of our knowledge, this is the first successful demonstration of the biological efficacy of LXA4 emulsion-loaded hydrogel systems on macrophage polarization. These versatile H-MELX and H-SELX formulations can be customized to enhance their biological activity making them promising tools to promote the resolution of inflammation in diverse clinical applications.

[Regeneration of dental tissues: Which biomaterials, which prospects?] / Régénération des tissus dentaires de soutien - Quels biomatériaux, quelles perspectives ?

Title: Régénération des tissus dentaires de soutien - Quels biomatériaux, quelles perspectives ? Abstract: Après avoir évoqué l'avenir des biomatériaux de réparation des tissus dentaires calcifiés (émail et dentine) en essayant d'être biomimétique et même de stimuler aux interfaces la régénération dentinaire1, nous évoquons dans cet article l'avenir des biomatériaux utilisés pour régénérer les tissus de soutien de la dent, le parodonte qui inclut l'os alvéolaire.

Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study.

OBJECTIVES: VEGF is prototypic marker of neovascularization, repeatedly proposed as intrinsic characteristic of peri-implantitis. This study aimed to assess pattern of VEGF in peri-implantitis, its correlation with titanium particles (TPs) and capacity as respective biomarker. MATERIAL AND METHODS: Pathological specificity of VEGF was assessed in peri-implant granulations using immunohistochemistry, periodontal granulations represented Ti-free positive controls. VEGF was correlated to TPs, identified using scanning electron microscopy coupled with dispersive x-ray spectrometry. Diagnostic accuracy, sensitivity and specificity of VEGF were estimated in PICF specimens from peri-implantitis, peri-implant mucositis (PIM) and healthy peri-implant tissues (HI) using machine learning algorithms. RESULTS: Peri-implantitis exhibited rich neovascular network with expressed density in contact zones toward neutrophil infiltrates without specific pattern variations around TPs, identified in all peri-implantitis specimens (mean particle size 8.9 ± 24.8 µm2; Ti-mass (%) 0.380 ± 0.163). VEGF was significantly more expressed in peri-implantitis (47,065 ± 24.2) compared to periodontitis (31,14 ± 9.15), and positively correlated with its soluble concentrations in PICF (p = 0.01). VEGF was positively correlated to all clinical endpoints and significantly increased in peri-implantitis compared to both PIM and HI, but despite high specificity (96%), its overall diagnostic capacity was average. Two patient clusters were identified in peri-implantitis, one with 8-fold higher VEGF values compared to HI, and second with lower values comparable to PIM. SIGNIFICANCE: VEGF accurately reflects neovascularization in peri-implantitis that was expressed in contact zones toward implant surface without specific histopathological patter variation around TPs. VEGF answered requests for biomarker of peri-implantitis but further research is necessary to decrypt its exact underlying cause.

Sustainable Biomass Lignin-Based Hydrogels: A Review on Properties, Formulation, and Biomedical Applications.

Different techniques have been developed to overcome the recalcitrant nature of lignocellulosic biomass and extract lignin biopolymer. Lignin has gained considerable interest owing to its attractive properties. These properties may be more beneficial when including lignin in the preparation of highly desired value-added products, including hydrogels. Lignin biopolymer, as one of the three major components of lignocellulosic biomaterials, has attracted significant interest in the biomedical field due to its biocompatibility, biodegradability, and antioxidant and antimicrobial activities. Its valorization by developing new hydrogels has increased in recent years. Furthermore, lignin-based hydrogels have shown great potential for various biomedical applications, and their copolymerization with other polymers and biopolymers further expands their possibilities. In this regard, lignin-based hydrogels can be synthesized by a variety of methods, including but not limited to interpenetrating polymer networks and polymerization, crosslinking copolymerization, crosslinking grafted lignin and monomers, atom transfer radical polymerization, and reversible addition-fragmentation transfer polymerization. As an example, the crosslinking mechanism of lignin-chitosan-poly(vinyl alcohol) (PVA) hydrogel involves active groups of lignin such as hydroxyl, carboxyl, and sulfonic groups that can form hydrogen bonds (with groups in the chemical structures of chitosan and/or PVA) and ionic bonds (with groups in the chemical structures of chitosan and/or PVA). The aim of this review paper is to provide a comprehensive overview of lignin-based hydrogels and their applications, focusing on the preparation and properties of lignin-based hydrogels and the biomedical applications of these hydrogels. In addition, we explore their potential in wound healing, drug delivery systems, and 3D bioprinting, showcasing the unique properties of lignin-based hydrogels that enable their successful utilization in these areas. Finally, we discuss future trends in the field and draw conclusions based on the findings presented.

Rat Perforator and Skin Vessels Vascular Mapping: An Original Anatomical Study About 140 Vessels and Literature Review.

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.

Effects of a New Soft Skills Metacognition Training Program on Self-Efficacy and Adaptive Performance.

Although soft skills training is called for by many scholars and managers, empirical studies on concrete training programs are scarce and do not always have the methodological rigor that is necessary to draw meaningful conclusions about their impact. In the present research, we investigate the effects of a new soft skills metacognition training program on self-efficacy and adaptive performance. To test these effects, we conducted an experiment with a sample of employees of a large firm (n = 180). The experiment included pre- and post-measurements and a control condition. The results suggested that participating in the training led to an increase in soft skills metacognition, self-efficacy, and four dimensions of adaptive performance, compared to a control condition. Mediation analyses suggested that an increase in soft skills metacognition led to an increase in self-efficacy, which led, in turn, to an increase in adaptive performance. Theoretical and practical implications are discussed, as well as limitations.

Injectable Hydrogel Membrane for Guided Bone Regeneration.

In recent years, multicomponent hydrogels such as interpenetrating polymer networks (IPNs) have emerged as innovative biomaterials due to the synergistic combination of the properties of each network. We hypothesized that an innovative non-animal IPN hydrogel combining self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) with photochemically cross-linkable dextran methacrylate (DexMA) could be a valid alternative to porcine collagen membranes in guided bone regeneration. Calvaria critical-size defects in rabbits were filled with synthetic biphasic calcium phosphate granules in conjunction with Si-HPMC; DexMA; or Si-HPMC/DexMA experimental membranes; and in a control group with a porcine collagen membrane. The synergistic effect obtained by interpenetration of the two polymer networks improved the physicochemical properties, and the gel point under visible light was reached instantaneously. Neutral red staining of murine L929 fibroblasts confirmed the cytocompatibility of the IPN. At 8 weeks, the photo-crosslinked membranes induced a similar degree of mineral deposition in the calvaria defects compared to the positive control, with 30.5 ± 5.2% for the IPN and 34.3 ± 8.2% for the collagen membrane. The barrier effect appeared to be similar in the IPN test group compared with the collagen membrane. In conclusion, this novel, easy-to-handle and apply, photochemically cross-linkable IPN hydrogel is an excellent non-animal alternative to porcine collagen membrane in guided bone regeneration procedures.

Transition from continuous to microglobular shaped peptide assemblies through a Liesegang-like enzyme-assisted mechanism.

Enzyme-assisted self-assembly confined within host materials leads to Liesegang-like spatial structuration when precursor peptides are diffusing through an enzyme-functionalized hydrogel. It is shown here that playing on peptide and enzyme concentrations results in a transition from continuous self-assembled peptide areas to individual microglobules. Their morphology, location, size and buildup mechanism are described. Additionally, it is also found that the enzymes adsorb onto the peptide self-assemblies leading to co-localization of peptide self-assembled microglobules and enzymes. Finally, we find that large microglobules grow at the expense of smaller ones present in their vicinity in a kind of Ostwald ripening process, illustrating the dynamic nature of the peptide self-assembly process within host hydrogels.

Standardized and axially vascularized calcium phosphate-based implants for segmental mandibular defects: A promising proof of concept.

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 cm3 in a relevant preclinical model, mimicking real life scenarii of segmental mandibular defect, with a full physiological regeneration of the defect after 12 months.

Embedding MSCs in Si-HPMC hydrogel decreased MSC-directed host immune response and increased the regenerative potential of macrophages.

Embedding mesenchymal stromal cells (MSCs) in biomaterial is a subject of increasing interest in the field of Regenerative Medicine. Speeding up the clinical use of MSCs is dependent on the use of non-syngeneic models in accordance with Good Manufacturing Practices (GMP) requirements and on costs. To this end, in this study, we analyzed the in vivo host immune response following local injection of silanized hydroxypropyl methylcellulose (Si-HPMC)-embedded human MSCs in a rat model developing colorectal damage induced by ionizing radiation. Plasma and lymphocytes from mesenteric lymph nodes were harvested in addition to colonic tissue. We set up tests, using flow cytometry and a live imaging system, to highlight the response to specific antibodies and measure the cytotoxicity of lymphocytes against injected MSCs. We demonstrated that Si-HPMC protects MSCs from specific antibodies production and from apoptosis by lymphocytes. We also observed that Si-HPMC does not modify innate immune response infiltrate in vivo, and that in vitro co-culture of Si-HPMC-embedded MSCs impacts macrophage inflammatory response depending on the microenvironment but, more importantly, increases the macrophage regenerative response through Wnt-family and VEGF gene expression. This study furthers our understanding of the mechanisms involved, with a view to improving the therapeutic benefits of biomaterial-assisted cell therapy by modulating the host immune response. The decrease in specific immune response against injected MSCs protected by Si-HPMC also opens up new possibilities for allogeneic clinical use.

Application of a Cryo-FIB-SEM-µRaman Instrument to Probe the Depth of Vitreous Ice in a Frozen Sample.

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).

Non-monotonous enzyme-assisted self-assembly profiles resulting from reaction-diffusion processes in host gels.

Reaction-diffusion (RD) processes are responsible for surface and in-depth micropatterning in inanimate and living matter. Here we show that enzyme-assisted self-assembly (EASA) of peptides is a valuable tool to functionnalize host gels. By using a phosphatase distributed in a host hydrogel, the diffusion of phosphorylated peptides from a liquid/host gel interface leads to the spontaneous formation of a pattern of dephosphorylated peptide self-assembly presenting at least two self-assembly maxima. Variation of enzyme and peptide concentrations change the pattern characteristics. When a peptide drop is deposited on a phosphatase functionalized gel, a self-assembly pattern is also formed both along the gel-solution interface and perpendicular to the interface. This self-assembly pattern induces a local change of the gel mechanical properties measured by nanoindentation. Its appearance relies on the formation of self-assembled structures by nucleation and growth processes which are static in the hydrogel. This process presents great similarities with the Liesegang pattern formation and must be taken into account for the functionalization of hydrogels by EASA. A mechanism based on RD is proposed leading to an effective mathematical model accounting for the pattern formation. This work highlights EASA as a tool to design organic Liesegang-like microstructured materials with potential applications in biomaterials and artificial living systems design.

Optimizing Full 3D SPARKLING Trajectories for High-Resolution Magnetic Resonance Imaging.

The Spreading Projection Algorithm for Rapid K-space sampLING, or SPARKLING, is an optimization-driven method that has been recently introduced for accelerated 2D MRI using compressed sensing. It has then been extended to address 3D imaging using either stacks of 2D sampling patterns or a local 3D strategy that optimizes a single sampling trajectory at a time. 2D SPARKLING actually performs variable density sampling (VDS) along a prescribed target density while maximizing sampling efficiency and meeting the gradient-based hardware constraints. However, 3D SPARKLING has remained limited in terms of acceleration factors along the third dimension if one wants to preserve a peaky point spread function (PSF) and thus good image quality. In this paper, in order to achieve higher acceleration factors in 3D imaging while preserving image quality, we propose a new efficient algorithm that performs optimization on full 3D SPARKLING. The proposed implementation based on fast multipole methods (FMM) allows us to design sampling patterns with up to 107 k-space samples, thus opening the door to 3D VDS. We compare multi-CPU and GPU implementations and demonstrate that the latter is optimal for 3D imaging in the high-resolution acquisition regime ( 600µ m isotropic). Finally, we show that this novel optimization for full 3D SPARKLING outperforms stacking strategies or 3D twisted projection imaging through retrospective and prospective studies on NIST phantom and in vivo brain scans at 3 Tesla taking the particular case of T2 *-w imaging. Overall the proposed method allows for 2.5-3.75x shorter scan times compared to GRAPPA-4 parallel imaging acquisition at 3 Tesla without compromising image quality.

Material-Assisted Strategies for Osteochondral Defect Repair.

The osteochondral (OC) unit plays a pivotal role in joint lubrication and in the transmission of constraints to bones during movement. The OC unit does not spontaneously heal; therefore, OC defects are considered to be one of the major risk factors for developing long-term degenerative joint diseases such as osteoarthritis. Yet, there is currently no curative treatment for OC defects, and OC regeneration remains an unmet medical challenge. In this context, a plethora of tissue engineering strategies have been envisioned over the last two decades, such as combining cells, biological molecules, and/or biomaterials, yet with little evidence of successful clinical transfer to date. This striking observation must be put into perspective with the difficulty in comparing studies to identify overall key elements for success. This systematic review aims to provide a deeper insight into the field of material-assisted strategies for OC regeneration, with particular considerations for the therapeutic potential of the different approaches (with or without cells or biological molecules), and current OC regeneration evaluation methods. After a brief description of the biological complexity of the OC unit, the recent literature is thoroughly analyzed, and the major pitfalls, emerging key elements, and new paths to success are identified and discussed.

Design and characterization of an in vivo injectable hydrogel with effervescently generated porosity for regenerative medicine applications.

Injectable hydrogels that polymerize directly in vivo hold significant promises in clinical settings to support the repair of damaged or failing tissues. Existing systems that allow cellular and tissue ingrowth after injection are limited because of deficient porosity and lack of oxygen and nutrient diffusion inside the hydrogels. Here is reported for the first time an in vivo injectable hydrogel in which the porosity does not pre-exist but is formed concomitantly with its in situ injection by a controlled effervescent reaction. The hydrogel tailorable crosslinking, through the reaction of polyethylene glycol with lysine dendrimers, allows the mixing and injection of precursor solutions from a dual-chamber syringe while entrapping effervescently generated CO2 bubbles to form highly interconnected porous networks. The resulting structures allow preserving modular mechanical properties (from 12.7 ± 0.9 to 29.9 ± 1.7 kPa) while being cytocompatible and conducive to swift cellular attachment, proliferation, in-depth infiltration and extracellular matrix deposition. Most importantly, the subcutaneously injected porous hydrogels are biocompatible, undergo tissue remodeling and support extensive neovascularisation, which is of significant advantage for the clinical repair of damaged tissues. Thus, the porosity and injectability of the described effervescent hydrogels, together with their biocompatibility and versatility of mechanical properties, open broad perspectives for various regenerative medicine or material applications, since effervescence could be combined with a variety of other systems of swift crosslinking. STATEMENT OF SIGNIFICANCE: A major challenge in hydrogel design is the synthesis of injectable formulations allowing easy handling and dispensing in the site of interest. However, the lack of adequate porosity inside hydrogels prevent cellular entry and, therefore, vascularization and tissue ingrowth, limiting the regenerative potential of a vast majority of injectable hydrogels. We describe here the development of an acellular hydrogel that can be injected directly in situ while allowing the simultaneous formation of porosity. Such hydrogel would facilitate handling through injection while providing a porous structure supporting vascularization and tissue ingrowth.

Refining the mandibular osteoradionecrosis rat model by in vivo longitudinal µCT analysis.

Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. Today, our lack of knowledge about the physiopathology restricts the development of new treatments. In this study, we refined the ORN rat model and quantitatively studied the progression of the disease. We tested the impact of radiation doses from 20 to 40 Gy, delivered with incident 4MV X-ray beams on the left mandible of the inbred Lewis Rat. We used micro-computed tomography (µCT) to obtain in vivo images for longitudinal bone imaging and ex vivo images after animal perfusion with barium sulphate contrast agent for vessel imaging. We compared quantification methods by analyzing 3D images and 2D measurements to determine the most appropriate and precise method according to the degree of damage. We defined 25 Gy as the minimum irradiation dose combined with the median molar extraction necessary to develop non-regenerative bone necrosis. µCT image analyses were correlated with clinical and histological analyses. This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures.

Injectable silanized hyaluronic acid hydrogel/biphasic calcium phosphate granule composites with improved handling and biodegradability promote bone regeneration in rabbits.

Biphasic calcium phosphate (BCP) granules are osteoconductive biomaterials used in clinics to favor bone reconstruction. Yet, poor cohesivity, injectability and mechanical properties restrain their use as bone fillers. In this study, we incorporated BCP granules into in situ forming silanized hyaluronic acid (Si-HA) and hydroxypropylmethylcellulose (Si-HPMC) hydrogels. Hydrogel composites were shown to be easily injectable (F < 30 N), with fast hardening properties (<5 min), and similar mechanical properties (E∼ 60 kPa). In vivo, both hydrogels were well tolerated by the host, but showed different biodegradability with Si-HA gels being partially degraded after 21d, while Si-HPMC gels remained stable. Both composites were easily injected into critical size rabbit defects and remained cohesive. After 4 weeks, Si-HPMC/BCP led to poor bone healing due to a lack of degradation. Conversely, Si-HA/BCP composites were fully degraded and beneficially influenced bone regeneration by increasing the space available for bone ingrowth, and by accelerating BCP granules turnover. Our study demonstrates that the degradation rate is key to control bone regeneration and that Si-HA/BCP composites are promising biomaterials to regenerate bone defects.

An Extrudable Partially Demineralized Allogeneic Bone Paste Exhibits a Similar Bone Healing Capacity as the "Gold Standard" Bone Graft.

Autologous bone grafts (BGs) remain the reference grafting technique in various clinical contexts of bone grafting procedures despite their numerous peri- and post-operative limitations. The use of allogeneic bone is a viable option for overcoming these limitations, as it is reliable and it has been widely utilized in various forms for decades. However, the lack of versatility of conventional allogeneic BGs (e.g., blocks, powders) limits their potential for use with irregular or hard-to-reach bone defects. In this context, a ready- and easy-to-use partially demineralized allogeneic BG in a paste form has been developed, with the aim of facilitating such bone grafting procedures. The regenerative properties of this bone paste (BP) was assessed and compared to that of a syngeneic BG in a pre-clinical model of intramembranous bone healing in critical size defects in rat calvaria. The microcomputed tridimensional quantifications and the histological observations at 7 weeks after the implantation revealed that the in vivo bone regeneration of critical-size defects (CSDs) filled with the BP was similar to syngeneic bone grafts (BGs). Thus, this ready-to-use, injectable, and moldable partially demineralized allogeneic BP, displaying equivalent bone healing capacity than the "gold standard," may be of particular clinical relevance in the context of oral and maxillofacial bone reconstructions.

A partially demineralized allogeneic bone graft: in vitro osteogenic potential and preclinical evaluation in two different intramembranous bone healing models.

In skeletal surgical procedures, bone regeneration in irregular and hard-to-reach areas may present clinical challenges. In order to overcome the limitations of traditional autologous bone grafts and bone substitutes, an extrudable and easy-to-handle innovative partially demineralized allogenic bone graft in the form of a paste has been developed. In this study, the regenerative potential of this paste was assessed and compared to its clinically used precursor form allogenic bone particles. Compared to the particular bone graft, the bone paste allowed better attachment of human mesenchymal stromal cells and their commitment towards the osteoblastic lineage, and it induced a pro-regenerative phenotype of human monocytes/macrophages. The bone paste also supported bone healing in vivo in a guide bone regeneration model and, more interestingly, exhibited a substantial bone-forming ability when implanted in a critical-size defect model in rat calvaria. Thus, these findings indicate that this novel partially demineralized allogeneic bone paste that combines substantial bone healing properties and rapid and ease-of-use may be a promising alternative to allogeneic bone grafts for bone regeneration in several clinical contexts of oral and maxillofacial bone grafting.