3D printed scaffolds of biosilica and spongin from marine sponges: analysis of genotoxicity and cytotoxicity for bone tissue repair.

Biosilica (BS) and spongin (SPG) from marine sponges are highlighted for their potential to promote bone regeneration. Moreover, 3D printing is introduced as a technology for producing bone grafts with optimized porous structures, allowing for better cell attachment, proliferation, and differentiation. Thus, this study aimed to characterize the BS and BS/SPG 3D printed scaffolds and to evaluate the biological effects in vitro. The scaffolds were printed using an ink containing 4 wt.% of sodium alginate. The physicochemical characteristics of BS and BS/SPG 3D printed scaffolds were analyzed by SEM, EDS, FTIR, porosity, evaluation of mass loss, and pH measurement. For in vitro analysis, the cellular viability of the MC3T3-E1 cell lineage was assessed using the AlamarBlue® assay and confocal microscopy, while genotoxicity and mineralization potential were evaluated through the micronucleus assay and Alizarin Red S, respectively. SEM analysis revealed spicules in BS, the fibrillar structure of SPG, and material degradation over the immersion period. FTIR indicated peaks corresponding to silicon oxide in BS samples and carbon oxide and amine in SPG samples. BS-SPG scaffolds exhibited higher porosity, while BS scaffolds displayed greater mass loss. pH measurements indicated a significant decrease induced by BS, which was mitigated by SPG over the experimental periods. In vitro studies demonstrated the biocompatibility and non-cytotoxicity of scaffold extracts. .Also, the scaffolds promoted cellular differentiation. The micronucleus test further confirmed the absence of genotoxicity. These findings suggest that 3D printed BS and BS/SPG scaffolds may possess desirable morphological and physicochemical properties, indicating in vitro biocompatibility.

Flounder fish (Paralichthys sp.) collagen a new tissue regeneration: genotoxicity, cytotoxicity and physical-chemistry characterization.

Collagen dressings have been widely used as effective treatments for chronic wounds acting as barrier, protecting the area from infections and participating in the healing process. Collagen from fish skin is biocompatible, presents low immunogenicity and is able of stimulating wound healing. In this scenario, skin of flounder fish (Paralichthys sp.) may constitute a promising source for collagen. Then, our hypothesis is that fish collagen is able of increasing cell proliferation, with no cytotoxicity. In this context, the aim of the present study was to investigate the physicochemical and morphological properties of collagen using scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), mass loss and pH. Moreover, the cytotoxicity and genotoxicity of collagen were studied using in vitro studies (cell viability, comet assay and micronucleus assay). Fish collagen showed no variation of pH and mass weight, with characteristic peaks of collagen in FTIR. Furthermore, all the extracts presented cell viability at least over 50% and no cytotoxicity was observed. Regarding genotoxicity data, the results showed that only the extract of 100% showed higher values in comparison with negative control group for CHO-K1 cell line as depicted by comet and micronucleus assays. Based on the results, it is suggested that fish collagen is biocompatible and present non-cytotoxicity in the in vitro studies, being considered a suitable material for tissue engineering proposals.

Fish collagen for skin wound healing: a systematic review in experimental animal studies.

Collagen extracted from fishes has been appearing as an alternative for commercial porcine and bovine collagen and it has been considered interesting especially for membrane manufacturing in tissue engineering. Despite the positive in vitro effects of fish collagen membranes, there is still no understanding of all the benefits that this natural biomaterial plays in the wound healing process, due to the lack of compilation of the results obtained in animal studies. In this sense, the purpose of this study was to perform a systematic review of the literature to examine the effects of fish collagen membranes for skin wound healing in experimental models of skin wound. The search was carried out according to the orientations of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the descriptors of the Medical Subject Headings (MeSH) were defined: "fish," collagen," "skin," and "in vivo". A total of 10 articles were retrieved from the databases PubMed and Scopus. After the elegibility analyses, this review covers the different origins of fish collagen reported in the different papers from the beginning of 2015 through the middle of 2021. The results were based mainly on histological analysis and macroscopic evaluation, and fish skin collagen was responsible for improving the wound healing rate and the process of reepithelization and collagen deposition. In conclusion, fish skin collagen has shown positive results in in vivo studies and may be a potential biomaterial in tissue engineering.

Metabolites from Marine Sponges and Their Potential to Treat Malarial Protozoan Parasites Infection: A Systematic Review.

Malaria is an infectious disease caused by protozoan parasites of the Plasmodium genus through the bite of female Anopheles mosquitoes, affecting 228 million people and causing 415 thousand deaths in 2018. Artemisinin-based combination therapies (ACTs) are the most recommended treatment for malaria; however, the emergence of multidrug resistance has unfortunately limited their effects and challenged the field. In this context, the ocean and its rich biodiversity have emerged as a very promising resource of bioactive compounds and secondary metabolites from different marine organisms. This systematic review of the literature focuses on the advances achieved in the search for new antimalarials from marine sponges, which are ancient organisms that developed defense mechanisms in a hostile environment. The principal inclusion criterion for analysis was articles with compounds with IC50 below 10 µM or 10 µg/mL against P. falciparum culture. The secondary metabolites identified include alkaloids, terpenoids, polyketides endoperoxides and glycosphingolipids. The structural features of active compounds selected in this review may be an interesting scaffold to inspire synthetic development of new antimalarials for selectively targeting parasite cell metabolism.

In vitro and in vivo biological performance of hydroxyapatite from fish waste.

The aim of this study was to evaluate biocompatibility of hydroxyapatite (HAP) from fish waste using in vitro and in vivo assays. Fish samples (whitemouth croaker - Micropogonias furnieri) from the biowaste was used as HAP source. Pre-osteoblastic MC3T3-E1 cells were used in vitro study. In addition, bone defects were artificially created in rat calvaria and filled with HAP in vivo. The results demonstrated that HAP reduced cytotoxicity in pre-osteoblast cells after 3 and 6 days following HAP exposure. DNA concentration was lower in the HAP group after 6 days. Quantitative RT-PCR did not show any significant differences (p > 0.05) between groups. In vivo study revealed that bone defects filled with HAP pointed out moderate chronic inflammatory cells with slight proliferation of blood vessels after 7 and 15 days. Chronic inflammatory infiltrate was absent after 30 days of HAP exposure. There was also a decrease in the amount of biomaterial, being followed by newly formed bone tissue. All experimental groups also demonstrated strong RUNX-2 immoexpression in the granulation tissue as well as in cells in close contact with biomaterial. The number of osteoblasts inside the defect area was lower in the HAP group when compared to control group after 7 days post-implantation. Similarly, the osteoblast surface as well as the percentage of bone surface was higher in control group when compared with HAP group after 7 days post-implantation. Taken together, HAP from fish waste is a promising possibility that should be explored more carefully by tissue-engineering or biotechnology.

Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.

The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice. At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+. Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants. At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization. However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP. Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants. In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation. Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN. J. Cell. Physiol. 232: 2528-2537, 2017. © 2016 Wiley Periodicals, Inc.

Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone.

Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins.

Absence of bone sialoprotein (BSP) alters profoundly hematopoiesis and upregulates osteopontin.

Matrix proteins of the SIBLING family interact with bone cells, extracellular matrix and mineral and are thus in a key position to regulate the microenvironment of the bone tissue, including its hematopoietic component. In this respect, osteopontin (OPN) has been implicated in the hematopoietic stem cell (HSC) niche as negative regulator of the HSC function. We investigated the impact on hematopoietic regulation of the absence of the cognate bone sialoprotein (BSP). BSP knockout (-/-) mice display increased bone marrow cellularity, and an altered commitment of hematopoietic precursors to myeloid lineages, leading in particular to an increased frequency of monocyte/macrophage cells. The B cell pool is increased in -/- bone marrow, and its composition is shifted toward more mature lymphocyte stages. BSP-null mice display a decreased HSC fraction among LSK cells and a higher percentage of more committed progenitors as compared to +/+. The fraction of proliferating LSK progenitors is higher in -/- mice, and after PTH treatment the mutant HSC pool is lower than in +/+. Strikingly, circulating levels of OPN as well as its expression in the bone tissue are much higher in the -/-. Thus, a BSP-null bone microenvironment affects the hematopoietic system both quantitatively and qualitatively, in a manner in part opposite to the OPN knockout, suggesting that the effects might in part reflect the higher OPN expression in the absence of BSP.

Terpenes extracted from marine sponges with antioxidant activity: a systematic review.

Marine biodiversity has emerged as a very promising resource of bioactive compounds and secondary metabolites from different sea organisms. The sponge's secondary metabolites demonstrated various bioactivities and potential pharmacological properties. This systematic review of the literature focuses on the advances achieved in the antioxidant potential of marine sponges in vitro. The review was performed in accordance with PRISMA guidelines. The main inclusion criterion for analysis was articles with identification of compounds from terpene classes that demonstrate antioxidant activity in vitro. Searching in three different databases, two hundred articles were selected. After screening abstracts, titles and evaluating for eligibility of manuscripts 14 articles were included. The most performed analyzes to detect antioxidant activity were scavenging activity 2,2-diphenyl-1-picrylhydrazyl (DPPH) and measurement of intracellular reactive oxygen species (ROS). It was possible to identify 17 compounds of the terpene class with pronounced antioxidant activity in vitro. Scientific evidence of the studies included in this review was accessed by the GRADE analysis. Terpenes play an important ecological role, moreover these molecules have a pharmaceutical and industrial application.

Anti-inflammatory Effects of Compounds Extracted from Marine Sponge s: A Systematic Review.

BACKGROUND: Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs. AIMS: Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential. METHODS: This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included. RESULTS: The results were based on in vivo and in vitro assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals. CONCLUSION: In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.

3D printed wound constructs for skin tissue engineering: A systematic review in experimental animal models.

Wound dressings are one of the most used treatments for chronic wounds. Moreover, 3D printing has been emerging as a promising strategy for printing 3D printed wound constructs, being able of manufacturing multi layers, with a solid 3D structure. Although all these promising effects of 3D printed wound constructs, there is still few studies and limited understanding of the interaction of these dressings with skin tissue and their effect on the process of skin wound healing. In this context, the aim of this work was to perform a systematic review of the literature to examine the effects of 3D printed wound constructs on the process of skin wound healing in animal models. The articles were selected from three databases following Medical Subject Headings (MeSH) descriptors "3D printing," "skin," "wound," and "in vivo." After the selection, exclusion and inclusion criteria, nine articles were analyzed. This review confirms the significant benefits of using 3D printed wound constructs for skin repair and regeneration. All the used inks demonstrated the ability of mimicking the structure of skin tissue and promoting cell adhesion, proliferation, migration, and mobility. Furthermore, in vivo findings showed full wound closure in most of the studies, with well-organized dermal and epidermal layers.

3D Printed Scaffolds Manufactured with Biosilica from Marine Sponges for Bone Healing in a Cranial Defect in Rats.

The inorganic part of marine sponges, called Biosilica (BS), presents an osteogenic potential and the ability of consolidating fractures. Moreover, 3D printing technique is highly effective for manufacturing scaffolds for tissue engineering proposals. Thus, the aims of this study were to characterize the 3D rinted scaffolds, to evaluate the biological effects in vitro and to investigate the in vivo response using an experimental model of cranial defects in rats. The physicochemical characteristics of 3D printed BS scaffolds were analyzed by FTIR, EDS, calcium assay, evaluation of mass loss and pH measurement. For in vitro analysis, the MC3T3-E1 and L929 cells viability was evaluated. For the in vivo evaluation, histopathology, morphometrical and immunohistochemistry analyses were performed in a cranial defect in rats. After the incubation, the 3D printed BS scaffolds presented lower values in pH and mass loss over time. Furthermore, the calcium assay showed an increased Ca uptake. The FTIR analysis indicated the characteristic peaks for materials with silica and the EDS analysis demonstrated the main presence of silica. Moreover, 3D printed BS demonstrated an increase in MC3T3-E1 and L929 cell viability in all periods analyzed. In addition, the histological analysis demonstrated no inflammation in days 15 and 45 post-surgery, and regions of newly formed bone were also observed. The immunohistochemistry analysis demonstrated increased Runx-2 and OPG immunostaining. Those findings support that 3D printed BS scaffolds may improve the process of bone repair in a critical bone defect as a result of stimulation of the newly formed bone.

Marine spongin incorporation into Biosilicate® for tissue engineering applications: An in vivo study.

Biomaterials and bone grafts, with the ability of stimulating tissue growth and bone consolidation, have been emerging as very promising strategies to treat bone fractures. Despite its well-known positive effects of biosilicate (BS) on osteogenesis, its use as bone grafts in critical situations such as bone defects of high dimensions or in non-consolidated fractures may not be sufficient to stimulate tissue repair. Consequently, several approaches have been explored to improve the bioactivity of BS. A promising strategy to reach this aim is the inclusion of an organic part, such as collagen, in order to mimic bone structure. Thus, the present study investigated the biological effects of marine spongin (SPG)-enriched BS composites on the process of healing, using a critical experimental model of cranial bone defect in rats. Histopathological and immunohistochemistry analyzes were performed after two and six weeks of implantation to investigate the effects of the material on bone repair (supplemental material-graphical abstract). Histological analysis demonstrated that for both BS and BS/SPG, similar findings were observed, with signs of material degradation, the presence of granulation tissue along the defect area and newly formed bone into the area of the defect. Additionally, histomorphometry showed that the control group presented higher values for Ob.S/BS (%) and for N.Ob/T.Ar (mm2) (six weeks post-surgery) compared to BS/SPG and higher values of N.Ob/T.Ar (mm2) compared to BS (two weeks post-surgery). Moreover, BS showed higher values for OV/TV (%) compared to BS/SPG (six weeks post-surgery). Also, VEGF immunohistochemistry was increased for BS (two weeks post-surgery) and for BS/SPG (six weeks) compared to CG. TGFb immunostaining was higher for BS compared to CG. The results of this study demonstrated that the BS and BS/SPG scaffolds were biocompatible and able to support bone formation in a critical bone defect in rats. Moreover, an increased VEGF immunostaining was observed in BS/SPG.

Evaluation of the In Vivo Biological Effects of Marine Collagen and Hydroxyapatite Composite in a Tibial Bone Defect Model in Rats.

One of the most promising strategies to improve the biological performance of bone grafts is the combination of different biomaterials. In this context, the aim of this study was to evaluate the effects of the incorporation of marine spongin (SPG) into Hydroxyapatite (HA) for bone tissue engineering proposals. The hypothesis of the current study is that SPG into HA would improve the biocompatibility of material and would have a positive stimulus into bone formation. Thus, HA and HA/SPG materials were produced and scanning electron microscopy (SEM) analysis was performed to characterize the samples. Also, in order to evaluate the in vivo tissue response, samples were implanted into a tibial bone defect in rats. Histopathological, immunohistochemistry, and biomechanical analyses were performed after 2 and 6 weeks of implantation to investigate the effects of the material on bone repair. The histological analysis demonstrated that composite presented an accelerated material degradation and enhanced newly bone formation. Additionally, histomorphometry analysis showed higher values of %BV/TV and N.Ob/T.Ar for HA/SPG. Runx-2 immunolabeling was higher for the composite group and no difference was found for VEGF. Moreover, the biomechanical analysis demonstrated similar values for all groups. These results indicated the potential of SPG to be used as an additive to HA to improve the biological performance for bone regeneration applications. However, further long-term studies should be carried out to provide additional information regarding the material degradation and bone regeneration.

Incorporation of collagen and PLGA in bioactive glass: in vivo biological evaluation.

Bioactive glasses (BG) are known for their unique ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not sufficient to produce bone consolidation. The use of composite materials may constitute an optimized therapeutical intervention for bone stimulation. The aim of this study was to characterize BG/collagen/poly (d,l-lactic-co-glycolic) acid (BG/COL/PLGA) composites, in vitro biocompatibility and in vivo biological properties. MC3T3-E1 cells were evaluated by cell proliferation, ALP activity, cell adhesion and morphology. Qualitative histology and immunohistochemistry were performed in a calvarial bone defect model in rats. The in vitro study demonstrated, after 3 and 6 days of culture, a significant increase of proliferation was observed for BG/PLGA compared to BG/COL and BG/COL/PLGA. BG/COL/PLGA presented a higher value for ALP activity after 3 days of culture compared to BG/PLGA. For in vivo analysis, 6 weeks post-surgery, BG/PLGA showed a more mature neoformed bone tissue. As a conclusion, the in vitro and in vivo studies pointed out that BG/PLGA samples improved biological properties in calvarial bone defects, highlighting the potential of BG/PLGA composites to be used as a bone graft for bone regeneration applications.

Photobiomodulation guided healing in a sub-critical bone defect in calvarias of rats.

BACKGROUND: Photobiomodulation presents stimulatory effects on tissue metabolism, constituting a promising strategy to produce bone tissue healing. OBJECTIVE: the aim of the present study was to investigate the in vivo performance of PBM using an experimental model of cranial bone defect in rats. MATERIAL AND METHODS: rats were distributed in 2 different groups (control group and PBM group). After the surgical procedure to induce cranial bone defects, PBM treatment initiated using a 808 nm laser (100 mW, 30 J/cm2, 3 times/week). After 2 and 6 weeks, animals were euthanized and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. RESULTS: Histology analysis demonstrated that for PBM most of the bone defect was filled with newly formed bone (with a more mature aspect when compared to CG). Histomorphomeric analysis also demonstrated a higher amount of newly formed bone deposition in the irradiated animals, 2 weeks post-surgery. Furthermore, there was a more intense deposition of collagen for PBM, with ticker fibers. Results from Runx-2 immunohistochemistry demonstrated that a higher immunostaining for CG 2 week's post-surgery and no other difference was observed for Rank-L immunostaining. CONCLUSION: This current study concluded that the use of PBM was effective in stimulating newly formed bone and collagen fiber deposition in the sub-critical bone defect, being a promising strategy for bone tissue engineering.

Hydroxyapatite from Fish for Bone Tissue Engineering: A Promising Approach.

Natural or synthetic hydroxyapatite (HA) has been frequently used as implant materials for orthopaedic and dental applications, showing excellent bioactivity, adequate mechanical rigidity and structure, osteoconductivity and angiogenic properties, no toxicity, and absence of inflammatory or antigenic reactions. HA can be easily synthesized or extracted from natural sources, such as bovine bone. However, the manufacturing costs to obtain HA are high, restricting the therapy. Herein, much effort has been paid for obtaning alternative natural sources for HA. The potential of HA extracted from skeleton of animals has been investigated. The aim of this review is to exploit the potential of HA derived from fish to fulfill biological activities for bone tissue engineering. In particular, HA from fish is easy to be manufactured regarding the majority of protocols that are based on the calcination method. Furthermore, the composition and structure of HA from fish were evaluated; the biomaterial showed good biocompatibility as a result of non-cytotoxicity and handling properties, demonstrating advantages in comparison with synthetic ones. Interestingly, another huge benefit brought by HA from bone fish is its positive effect for environment since this technique considerably reduces waste. Certainly, the process of transforming fish into HA is an environmentally friendly process and stands as a good chance for reducing costs of treatment in bone repair or replacement with little impact into the environment.

Natural marine sponges for bone tissue engineering: The state of art and future perspectives.

Marine life and its rich biodiversity provide a plentiful resource of potential new products for the society. Remarkably, marine organisms still remain a largely unexploited resource for biotechnology applications. Among them, marine sponges are sessile animals from the phylum Porifera dated at least from 580 million years ago. It is known that molecules from marine sponges present a huge therapeutic potential in a wide range of applications mainly due to its antitumor, antiviral, anti-inflammatory, and antibiotic effects. In this context, this article reviews all the information available in the literature about the potential of the use of marine sponges for bone tissue engineering applications. First, one of the properties that make sponges interesting as bone substitutes is their structural characteristics. Most species have an efficient interconnected porous architecture, which allows them to process a significant amount of water and facilitates the flow of fluids, mimicking an ideal bone scaffold. Second, sponges have an organic component, the spongin, which is analogous to vertebral collagen, the most widely used natural polymer for tissue regeneration. Last, osteogenic properties of marine sponges is also highlighted by their mineral content, such as biosilica and other compounds, that are able to support cell growth and to stimulate bone formation and mineralization. This review focuses on recent studies concerning these interesting properties, as well as on some challenges to be overcome in the bone tissue engineering field. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1717-1727, 2017.

The role of the SIBLING, Bone Sialoprotein in skeletal biology - Contribution of mouse experimental genetics.

Bone Sialoprotein (BSP) is a member of the "Small Integrin-Binding Ligand N-linked Glycoproteins" (SIBLING) extracellular matrix protein family of mineralized tissues. BSP has been less studied than other SIBLING proteins such as Osteopontin (OPN), which is coexpressed with it in several skeletal cell types. Here we review the contribution of genetically engineered mice (BSP gene knockout and overexpression) to the understanding of the role of BSP in the bone organ. The studies made so far highlight the role of BSP in skeletal mineralization, as well as its importance for proper osteoblast and osteoclast differentiation and activity, most prominently in primary/repair bone. The absence of BSP also affects the local environment of the bone tissue, in particular hematopoiesis and vascularization. Interestingly, lack of BSP induces an overexpression of OPN, and the cognate protein could be responsible for some aspects of the BSP gene knockout skeletal phenotype, while replacing BSP for some of its functions. Such interplay between the partly overlapping functions of SIBLING proteins, as well as the network of cross-regulations in which they are involved should now be the focus of further work.