Collagen Mineralization Research Articles

Mechanically enhanced biodegradable scaffold based on SF microfibers for repairing bone defects in the distal femur of rats

Silk-based biodegradable materials play an important role in tissue engineering, especially in the field of bone regeneration. However, while optimizing mechanical properties and bone regeneration characteristics, modified silk fibroin (SF)-based materials also increase the complexity of scaffold systems, which is not conducive to clinical translation. In this study, we first added synthetic biomimetic mineralized collagen (MC) particles to SF-based materials to improve the bone regeneration properties of the scaffolds and simultaneously regulated the degradation rate of the scaffolds to match the bone regeneration rate. Second, SF microfibers were prepared by hydrolysis with alkaline heating and added to SFMC scaffolds with excellent osteogenic stimulation ability to prepare SF microfiber (mf)-modified SFMC-mf scaffolds with excellent mechanical properties, whose compression modulus increased from 4.58±0.23 MPa to 14.63±0.88 MPa. Finally, the SFMC-mf scaffold was implanted into the weight-bearing bone defect area of the distal femur of rats, and the results showed that the SFMC-mf scaffold significantly promoted functional recovery of the affected limb and increased the amount of new bone in the defect area compared with those in the SFC-mf group and the blank control group. In addition, the RNA-seq results suggested that the genes with upregulated expression in the SFMC-mf scaffold group were mainly enriched in vascular regeneration. In conclusion, this SF microfiber modification method effectively improved the mechanical properties of SFMC scaffolds without moving the SF scaffold system in the direction of compositional complexity, providing new insights for the subsequent development of more effective bionic repair materials for bone defects and assisting in their clinical translation.

Biomimetic mineralization of collagen from fish scale to construct a functionally gradient lamellar bone-like structure for guided bone regeneration

Wide used guided bone regeneration (GBR) membrane materials, such as collagen, Teflon, and other synthesized polymers, present a great challenge in term of integrating the mechanical property and degradation rate when addressing critical bone defects. Therefore, inspired by the distinctive architecture of fish scales, this study utilized epigallocatechin gallate to modify decellularized fish scales following biomimetic mineralization to fabricate a GBR membrane that mimics the structure of lamellar bone. The structure, physical and chemical properties, and biological functions of the novel GBR membrane were evaluated. Results indicate that the decellularized fish scale with 5 remineralization cycles (5R-E-DCFS) exhibited a composite and structure similar to natural bone and had a special functionally gradient mineral contents character, demonstrating excellent mechanical properties, hydrophilicity, and degradation properties. In vitro, the 5R-E-DCFS membrane exhibited excellent cytocompatibility promoting Sprague-Dawley (SD) rat bone marrow mesenchymal stem cell proliferation and differentiation up-regulating the expression of osteogenic-related genes and proteins. Furthermore, in vivo, the 5R-E-DCFS membrane promoted the critical skull bone defects of SD rats repairment and regeneration. Therefore, this innovative biomimetic membrane holds substantial clinical potential as an ideal GBR membrane with mechanical properties for space-making and suitable degradation rate for bone regeneration to manage bone defects.

Correlative Raman spectroscopy and electron microscopy identifies glycogen rich deposits correlated with local structural defects in long bones of type IV osteogenesis imperfecta patients

Osteogenesis imperfecta (OI) is a genetic bone disease occurring in approximately 1 in 10,000 births, usually as a result of genetic mutation. OI patients suffer from increased fracture risk and - depending on the severity of the disease - deformation of the limbs, which can even lead to perinatal death.Despite extensive studies, the way in which the genetic mutation is translated into structural and compositional anomalies of the tissue is still an open question. Different observations have been reported, ranging from no structural (or chemical) differences to completely chaotic bone structure and composition.Here, we investigated bone samples from two adolescent OI-IV patients, focusing on the bone structure and chemistry in naturally occurring fractures. The exposed fracture plane allows the investigation of the structure and composition of the weakest bone plane. We do so by combining scanning electron microscopy (SEM) imaging with chemical information from Raman microscopy.The exposed fracture planes show different regions within the same tissue, displaying normal osteonal structures next to disorganized osteons and totally disordered structures, while the collagen mineralization in all cases is similar to that of a healthy bone.In addition, we also detected significant amounts of depositions of glycogen-rich, organic, globules of 250-1000nm in size. These depositions point to a role of cellular disfunction in the disorganization of the collagen in qualitative OI.Overall, our results unite multiple, sometimes contradicting views from the literature on qualitative OI.

Revealing chemistry-structure-function relationships in shark vertebrae across length scales

Shark cartilage presents a complex material composed of collagen, proteoglycans, and bioapatite. In the present study, we explored the link between microstructure, chemical composition, and biomechanical function of shark vertebral cartilage using Polarized Light Microscopy (PLM), Atomic Force Microscopy (AFM), Confocal Raman Microspectroscopy, and Nanoindentation. Our investigation focused on vertebrae from Blacktip and Shortfin Mako sharks. As typical representatives of the orders Carcharhiniformes and Lamniformes, these species differ in preferred habitat, ecological role, and swimming style. We observed structural variations in mineral organization and collagen fiber arrangement using PLM and AFM. In both sharks, the highly calcified corpus calcarea shows a ridged morphology, while a chain-like network is present in the less mineralized intermedialia. Raman spectromicroscopy demonstrates a relative increase of glucosaminocycans (GAGs) with respect to collagen and a decrease in mineral-rich zones, underlining the role of GAGs in modulating bioapatite mineralization. Region-specific testing confirmed that intravertebral variations in mineral content and arrangement result in distinct nanomechanical properties. Local Young's moduli from mineralized regions exceeded bulk values by a factor of 10. Overall, this work provides profound insights into a flexible yet strong biocomposite, which is crucial for the extraordinary speed of cartilaginous fish in the worlds’ oceans. Statement of significanceShark cartilage is a morphologically complex material composed of collagen, sulfated proteoglycans, and calcium phosphate minerals. This study explores the link between microstructure, chemical composition, and biological mechanical function of shark vertebral cartilage at the micro- and nanometer scale in typical Carcharhiniform and Lamniform shark species, which represent different vertebral mineralization morphologies, swimming styles and speeds. By studying the intricacies of shark vertebrae, we hope to lay the foundation for biomimetic composite materials that harness lamellar reinforcement and tailored stiffness gradients, capable of dynamic and localized adjustments during movement.

An enhanced tri-layer bionic periosteum with gradient structure loaded by mineralized collagen for guided bone regeneration and in-situ repair

Severe fracture non-union often accompanied by damaged or even absent periosteum remains a significant challenge. This paper presents a novel tri-layer bionic periosteum with gradient structure and mineralized collagen (MC) mimics natural periosteum for in-situ repair and bone regeneration. The construct with ultrasonic polylactic acid as the loose outer fibrous layer (UPLA), poly(ε-caprolactone) as the intermediate barrier layer (PCL-M), and poly(ε-caprolactone)/MC as the inner osteoblastic layer (PM) was prepared. The physicochemical properties of layers were investigated. UPLA/PCL-M/PM exhibited a tensile strength (3.55 ± 0.23 MPa) close to that of natural periosteum and excellent adhesion between the layers. In vitro experiments demonstrated that all layers had no toxicity to cells. UPLA promoted inward growth of mouse fibroblasts. PCL-M with a uniform pore size (2.82 ± 0.05 μm) could achieve a barrier effect against fibroblasts according to the live/dead assay. Meanwhile, PM could effectively promote cell migration with high alkaline phosphatase expression and significant mineralization of the extracellular matrix. Besides, in vivo experiments showed that UPLA/PCL-M/PM significantly promoted the regeneration of bone and early angiogenesis. Therefore, this construct with gradient structure developed in this paper would have great application potential in the efficient and high-quality treatment of severe fractures with periosteal defects.

Changes of the Alveolar Bone Ridge Using Bone Mineral Grafts and Collagen Membranes after Tooth Extraction: A Systematic Review and Meta-Analysis.

Alveolar preservation techniques for esthetic or functional purposes, or both, are a frequently used alternative for the treatment of post-extraction sockets, the aim of which is the regeneration of the lesion and the preservation of the alveolar bone crest. Studies published in PubMed (Medline), Web of Science, Embase, and Cochrane Library databases up to January 2024 were consulted. Inclusion criteria were established as intervention studies, according to the PICOs strategy: adult subjects undergoing dental extractions (participants), with alveoli treated with bone mineral grafts and collagen membranes (intervention), compared to spontaneous healing (comparison), and observing the response to treatment in clinical and radiological measures of the alveolar bone crest (outcomes). We obtained 561 results and selected 12 studies. Risk of bias was assessed using the Cochrane Risk of Bias Tool, and methodological quality was assessed using the Joanna Briggs Institute. Due to the high heterogeneity of the studies (I2 > 75%), a random-effects meta-analysis was used. Despite the trend, no statistical significance (p > 0.05) was found in the experimental groups. The use of bone mineral grafts in combination with resorbable collagen barriers provides greater preservation of the alveolar ridge, although more clinical studies are needed.

Curved mineral platelets in bone

Bone is a composite material principally made up of a mineral phase (apatite) and collagen fibrils. The mineral component of bone occurs in the form of polycrystalline platelets 2–6 nm in thickness. These platelets are packed and probably glued together in stacks of two or more, ranging up to >30 platelets. Here we show that most of these stacks are curved flat sheets whose cylindrical axes are oriented parallel to the long axes of collagen fibrils. Consequently, the curvature of the platelets is not detectable in TEM sections cut parallel to the collagen fibril axes. The radius of curvature around these axes ranges from about 25 nm (the average radius of the collagen fibrils) to 100′s of nm. The shapes of these curved forms contribute to the compressive strength of bone. Statement of significanceBone, the material of which bones are made, is mainly composed of a protein, collagen, and the mineral apatite (calcium phosphate). The crystals have long been known to be flat plates about 5 nanometers (nm) thick. Here we show that the crystals are bound together in curved platelets with a radius of curvature between 25 and several hundred nm, which weave between fibrils of collagen. Some platelets wrap tightly around fibrils. The platelets form stacks of from two to up to 30. The crystals in the platelets are all oriented parallel to the cylindrical fibrils even though most crystals are not in contact with collagen. These curved structures provide greater strength to bone.

Asporin expression is associated with human atherosclerotic plaque integrity

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This work was supported by the Swedish Research Council, the Swedish Heart and Lung Foundation, Skåne University Hospital funds Background Calcification serves as a clinical marker of atherosclerotic plaque burden. Recent studies have also shed light on its intricate association with plaque vulnerability, likely depend on calcification structures and the surrounding environment. Asporin (ASPN) is a member of the small-leucine-rich proteoglycans that contains a unique and well-conserved stretch of aspartate (D) residues, which mimic the role of glycosaminoglycans. Via its D-repeat, ASPN can interact with calcium and several other extracellular matrix molecules, thus influencing collagen mineralization and TGF-β signaling. ASPN expression has been shown to be higher in asymptomatic compared to symptomatic atherosclerotic plaques, suggesting a potential protective role. However, the role of ASPN in maintaining plaque integrity remains unknown. Purpose Here we aimed to explore the role of ASPN in atherosclerosis, by investigating if ASPN was expressed in human carotid plaques and by determining if ASPN is associated with risk for postoperative cardiovascular events and death. Methods ASPN and TGF-β protein levels were measured by ELISA and Milliplex in 176 human plaque tissue homogenates obtained from the Carotid Plaque Imaging Project (CPIP) biobank. Plaque tissue sections were stained for ASPN, destabilizing (CD68, oil red O, glycophorin A) and stabilizing plaque components (Movat, α-actin). Plaque tissue RNA expression levels were assessed in 82 plaques using bulk RNA sequencing. Plaque levels of phosphate, elastin and collagen were measured using ELISA. Results ASPN protein levels were higher in plaques from asymptomatic patients compared to symptomatic patients (p=0.011). ASPN RNA levels correlated positively to RNA levels of the smooth muscle cell markers ACTA2, MYH11 and TAGLN. Moreover, protein levels correlated with plaque levels of phosphate (r=0.258, p=0.001), elastin (r=0.423, p<0.001), collagen (r=0.248, p=0.002) and stability factors like the TGF-β family members, TGF-β1 (r=0.176, p=0.035), TGF-β2 (r=0.581, p<0.001) and TGF-β3 (r=0.396, p<0.001). Furthermore, plaque ASPN protein concentration, correlated inversely with a histological plaque vulnerability index (r=-0.265, p=0.0029), which is ratio between the plaque area of destabilizing (macrophages, lipids, intra-plaque hemorrhage) and stabilizing plaque components (collagen and smooth muscle cells). Additionally, above median ASPN levels were associated with lower risk for postoperative cardiovascular events (p=0.008) and death (p=0.009). Conclusion Our findings suggest that elevated levels of ASPN might have a crucial role in maintaining plaque stability, affecting plaque calcification.

Bone collagen tensile properties of the aging human proximal femur

Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this context, collagen content and integrity are considered important factors, although limited research has been conducted on the tensile behavior of demineralized compact bone in relation to its porosity and elastic properties in the native mineralized state. Therefore, this study aims (i) at examining the age-dependency of mineralized bone and collagen micromechanical properties; (ii) to test whether, and if so to which extent, collagen properties contribute to mineralized bone mechanical properties.Two cylindrical cortical bone samples from fresh frozen human anatomic donor material were extracted from 80 proximal diaphyseal sections from a cohort of 24 female and 19 male donors (57 to 96 years at death). One sample per section was tested in uniaxial tension under hydrated conditions. First, the native sample was tested elastically (0.25 % strain), and after demineralization, up to failure. Morphology and composition of the second specimen was assessed using micro-computed tomography, Raman spectroscopy, and gravimetric methods. Simple and multiple linear regression were employed to relate morphological, compositional, and mechanical variables with age and sex.Macro-tensile properties revealed that only elastic modulus of native samples was age dependent whereas apparent elastic modulus was sex dependent (p < 0.01). Compositional and morphological analysis detected a weak but significant age and sex dependency of relative mineral weight (r = −0.24, p < 0.05) and collagen disorder ratio (I∼1670/I∼1640, r = 0.25, p < 0.05) and a strong sex dependency of bone volume fraction while generally showing consistent results in mineral content assessment. Young's modulus of demineralized bone was significantly related to tissue mineral density and Young's modulus of native bone.The results indicate that mechanical properties of the organic phase, that include collagen and non-collagenous proteins, are independent of donor age. The observed reduction in relative mineral weight and corresponding overall stiffer response of the collagen network may be caused by a reduced number of mineral-collagen connections and a lack of extrafibrillar and intrafibrillar mineralization that induces a loss of waviness and a collagen fiber pre-stretch.

Equilibrium interactions of biomimetic DNA aptamers produce intrafibrillar calcium phosphate mineralization of collagen

Native and biomimetic DNA structures have been demonstrated to impact materials synthesis under a variety of conditions but have only just begun to be explored in this role compared to other biopolymers such as peptides, proteins, polysaccharides, and glycopolymers. One selected DNA aptamer has been explored in calcium phosphate and calcium carbonate mineralization, demonstrating sequence-dependent control of kinetics, morphology, and crystallinity. This aptamer is here applied to a biologically-relevant bone model system that uses collagen hydrogels. In the presence of the aptamer, intrafibrillar collagen mineralization is observed compared to negative controls and a positive control using well-studied poly-aspartic acid. The mechanism of interaction is explored through affinity measurements, kinetics of calcium uptake, and kinetics of aptamer uptake into the forming mineral. There is a marked difference observed between the selected aptamer containing a G-quadruplex secondary structure compared to a control sequence with no G-quadruplex. It is hypothesized that the equilibrium interaction of the aptamer with calcium-phosphate precursors and with the collagen itself leads to slow kinetic mineral formation and a morphology appropriate to bone. This points to new uses for DNA aptamers in biologically-relevant mineralization systems and the possibility of future biomedical applications. Statement of significanceCollagen is the protein structural component that mineralizes with calcium phosphate to form durable bone. Crystalline calcium phosphate must be infused throughout the collagen fiber structure to produce a strong material. This process is assisted by soluble proteins that interact with both calcium phosphate precursors and the collagen protein and has been proposed to follow a polymer-induce liquid precursor (PILP) model. Further understanding of this model and control of the process through synthetic, biomimetic molecules could have significant advantages in biomedical, restorative procedures. For the first time, synthetic DNA aptamers with specific secondary structures are here shown to influence and direct collagen mineralization. The mechanism of this process has been studied to demonstrate an important equilibrium between the DNA aptamer, calcium phosphate precursors, and collagen.

Promoting bond durability by a novel fabricated bioactive dentin adhesive

ObjectiveTo prepare a bioactive dentin adhesive and investigate its effect on promoting bonding durability of dentin. MethodsThe mineralization of the bioactive glass with high phosphorus (10.8 mol% P2O5–54.2 mol% SiO2–35 mol% CaO, named PSC) and its ability to induce type I collagen mineralization were observed by SEM and TEM. The Control-Bond and the bioactive dentin adhesive containing 20 wt% PSC particles (PSC-Bond) were prepared, and their degree of conversion (DC), microtensile bond strength (μTBS), film thickness and mineralization performance were evaluated. To evaluate the bonding durability, dentin bonding samples were prepared by Control-Bond and PSC-Bond, and mineralizated in simulated body fluid for 24 h, 3 months, and 6 months. Then, the long-term bond strength and microleakage at the adhesive interface of dentin bonding samples were evaluated by microtensile testing and semiquantitative ELIASA respectively. ResultsThe PSC showed superior mineralization at 24 h and induced type I collagen mineralization to some extent under weakly alkaline conditions. For PSC-Bond, DC was 62.65 ± 1.20%, μTBS was 39.25 ± 4.24 MPa and film thickness was 17.00 ± 2.61 μm. PSC-Bond also formed hydroxyapatite and maintained good mineralization at the bonding interface. At 24 h, no significant differences in μTBS and interface microleakage were observed between the Control-Bond and PSC-Bond groups. After 6 months of aging, the μTBS was significantly higher and the interface microleakage was significantly lower of PSC-Bond group than those of Control-Bond group. SignificancePSC-Bond maintained bond strength stability and reduced interface microleakage to some extent, possibly reducing the occurrence of secondary caries, while maintaining long-term effectiveness of adhesive restorations.

Janus Membrane with Intrafibrillarly Strontium-Apatite-Mineralized Collagen for Guided Bone Regeneration.

Commercial collagen membranes face difficulty in guided bone regeneration (GBR) due to the absence of hierarchical structural design, effective interface management, and diverse bioactivity. Herein, a Janus membrane called SrJM is developed that consists of a porous collagen face to enhance osteogenic function and a dense face to maintain barrier function. Specifically, biomimetic intrafibrillar mineralization of collagen with strontium apatite is realized by liquid precursors of amorphous strontium phosphate. Polycaprolactone methacryloyl is further integrated on one side of the collagen as a dense face, which endows SrJM with mechanical support and a prolonged lifespan. In vitro experiments demonstrate that the dense face of SrJM acts as a strong barrier against fibroblasts, while the porous face significantly promotes cell adhesion and osteogenic differentiation through activation of calcium-sensitive receptor/integrin/Wnt signaling pathways. Meanwhile, SrJM effectively enhances osteogenesis and angiogenesis by recruiting stem cells and modulating osteoimmune response, thus creating an ideal microenvironment for bone regeneration. In vivo studies verify that the bone defect region guided by SrJM is completely repaired by newly formed vascularized bone. Overall, the outstanding performance of SrJM supports its ongoing development as a multifunctional GBR membrane, and this study provides a versatile strategy of fabricating collagen-based biomaterials for hard tissue regeneration.

Collagen Mineralization Decreases NK Cell-Mediated Cytotoxicity of Breast Cancer Cells via Increased Glycocalyx Thickness.

Skeletal metastasis is common in patients with advanced breast cancer and often caused by immune evasion of disseminated tumor cells (DTCs). In the skeleton, tumor cells not only disseminate to the bone marrow but also to osteogenic niches in which they interact with newly mineralizing bone extracellular matrix (ECM). However, it remains unclear how mineralization of collagen type I, the primary component of bone ECM, regulates tumor-immune cell interactions. Here, a combination of synthetic bone matrix models with controlled mineral content, nanoscale optical imaging, and flow cytometry are utilized to evaluate how collagen type I mineralization affects the biochemical and biophysical properties of the tumor cell glycocalyx, a dense layer of glycosylated proteins and lipids decorating their cell surface. These results suggest that collagen mineralization upregulates mucin-type O-glycosylation and sialylation by tumor cells, which increases their glycocalyx thickness while enhancing resistance to attack by natural killer (NK) cells. These changes are functionally linked as treatment with a sialylation inhibitor decreased mineralization-dependent glycocalyx thickness and made tumor cells more susceptible to NK cell attack. Together, these results suggest that interference with glycocalyx sialylation may represent a therapeutic strategy to enhance cancer immunotherapies targeting bone-metastatic breast cancer.

Dual-functional 3D-printed porous bioactive scaffold enhanced bone repair by promoting osteogenesis and angiogenesis

The treatment of bone defects is a difficult problem in orthopedics. The excessive destruction of local bone tissue at defect sites destroys blood supply and renders bone regeneration insufficient, which further leads to delayed union or even nonunion. To solve this problem, in this study, we incorporated icariin into alginate/mineralized collagen (AMC) hydrogel and then placed the drug-loaded hydrogel into the pores of a 3D-printed porous titanium alloy (AMCI/PTi) scaffold to prepare a bioactive scaffold with the dual functions of promoting angiogenesis and bone regeneration. The experimental results showed that the ACMI/PTi scaffold had suitable mechanical properties, sustained drug release function, and excellent biocompatibility. The released icariin and mineralized collagen (MC) synergistically promoted angiogenesis and osteogenic differentiation in vitro. After implantation into a rabbit radius defect, the composite scaffold showed a satisfactory effect in promoting bone repair. Therefore, this composite dual-functional scaffold could meet the requirements of bone defect treatment and provide a promising strategy for the repair of large segmental bone defects in clinic.

Decorin in the spatial control of collagen mineralization.

Understanding the molecular mechanism by which the periodontal ligament (PDL) is maintained uncalcified between two mineralized tissues (cementum and bone) may facilitate the functional repair and regeneration of the periodontium complex, disrupted in the context of periodontal diseases. However, research that explores the control of type I collagen (COL I) mineralization fails to clarify the detailed mechanism of regulating spatial collagen mineralization, especially in the periodontium complex. In the present study, decorin (DCN), which is characterized as abundant in the PDL region and rare in mineralized tissues, was hypothesized to be a key regulator in the spatial control of collagen mineralization. The circular dichroism results confirmed that DCN regulated the secondary structure of COL I, and the surface plasmon resonance results indicated that COL I possessed a higher affinity for DCN than for other mineralization promoters, such as DMP-1, OPN, BSP and DSPP. These features of DCN may contribute to blocking intrafibrillar mineralization in COL I fibrils during the polymer-induced liquid-precursor mineralization process when the fibrils are cross-linked with DCN. This effect was more remarkable when the fibrils were phosphorylated by sodium trimetaphosphate, as shown by the observation of a tube-like morphology via TEM and mineral sheath via SEM. This study enhances the understanding of the role of DCN in mineralization regulation among periodontal tissues. This provides insights for the development of biomaterials for the regeneration of interfaces between soft and hard tissues.

Intrafibrillar mineralization of type I collagen with calcium carbonate and strontium carbonate induced by polyelectrolyte-cation complexes.

Calcium carbonate (CaCO3), possessing excellent biocompatibility, bioactivity, osteoconductivity and superior biodegradability, may serve as an alternative to hydroxyapatite (HAp), the natural inorganic component of bone and dentin. Intrafibrillar mineralization of collagen with CaCO3 was achieved through the polymer-induced liquid precursor (PILP) process for at least 2 days. This study aims to propose a novel pathway for rapid intrafibrillar mineralization with CaCO3 by sequential application of the carbonate-bicarbonate buffer and polyaspartic acid (pAsp)-Ca suspension. Fourier transform infrared (FTIR) spectroscopy, zeta potential measurements, atomic force microscopy/Kelvin probe force microscopy (AFM/KPFM), and three-dimensional stochastic optical reconstruction microscopy (3D STORM) demonstrated that the carbonate-bicarbonate buffer significantly decreased the surface potential of collagen and CO32-/HCO3- ions could attach to collagen fibrils via hydrogen bonds. The electropositive pAsp-Ca complexes and free Ca2+ ions are attracted to and interact with CO32-/HCO3- ions through electrostatic attractions to form amorphous calcium carbonate that crystallizes gradually. Moreover, like CaCO3, strontium carbonate (SrCO3) can deposit inside the collagen fibrils through this pathway. The CaCO3-mineralized collagen gels exhibited better biocompatibility and cell proliferation ability than SrCO3. This study provides a feasible strategy for rapid collagen mineralization with CaCO3 and SrCO3, as well as elucidating the tissue engineering of CaCO3-based biomineralized materials.

ACP‐Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism (Adv. Healthcare Mater. 2/2024)

ACP‐Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism (Adv. Healthcare Mater. 2/2024)

Polyelectrolyte-Cation Complexes Using PAsp-Sr Complexes Induce Biomimetic Mineralization with Antibacterial Ability.

Remineralized dentin with an antibacterial ability is still a significant challenge in dentistry. Previously, a polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for rapid collagen mineralization. In the present study, the expansion concept of the PCCP process is explored by replacing the calcium with other cations, such as strontium. The results of transmission electron microscopy (TEM), 3D stochastic optical reconstruction microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and high-resolution TEM with selected area electron diffraction demonstrate that biomimetic mineralization of collagen fibrils and demineralized dentin could be fulfilled with Sr&F-codoped hydroxyapatite (HAp) after they are treated with poly-aspartic acid-strontium (PAsp-Sr) suspension followed by a phosphate&fluoride solution. Moreover, dentin remineralized with Sr&F-codoped HAp exhibits in vitro and in vivo antibacterial ability against Streptococcus mutans. The cytotoxicity and oral mucosa irritation tests reveal excellent biocompatibility of mineralization mediums (PAsp-Sr suspension and phosphate&fluoride solution). The demineralized dentin's mechanical properties (elastic modulus and microhardness) could be restored almost to that of the intact dentin. Hence, the expansion concept of the PCCP process that replaces calcium ions with some cationic ions along with fluorine opens up new horizons for generating antibacterial remineralized dentin containing ions-doped HAp with excellent biocompatibility via biomimetic mineralization technology.

Functionalized biomimetic mineralized collagen promotes osseointegration of 3D-printed titanium alloy microporous interface

Mineralized collagen (MC) is the fundamental unit of natural bone tissue and can induce bone regeneration. Unmodified MC has poor mechanical properties and a single component, making it unable to cope with complex physiological environment. In this study, we introduced sodium alginate (SA) and vascular endothelial growth factor (VEGF) into the MC material to construct functionalized mineralized collagen (FMC) with good mechanical strength and the ability to continuously release growth factors. The FMC is filled into the pores of 3D printed titanium alloy scaffold to form a new organic-inorganic bioactive interface. With the continuous degradation of FMC, bone marrow mesenchymal stem cells (BMSCs) and vascular endothelial cells (VECs) in the surrounding environment are recruited to the surface of the scaffold to promote bone and vascular regeneration. After implanting the scaffold into the distal femoral defect of rabbits, Micro CT, histological, push-out, as well as immunohistochemical analysis showed that the composite interface can significantly promote osseointegration. These findings provide a new strategy for the development and application of mineralized collagen materials.

Rapid Intrafibrillar Mineralization Strategy Enhances Adhesive–Dentin Interface

Biomimetic mineralization of dentin collagen appears to be a promising strategy to optimize dentin bonding durability. However, traditional postbonding mineralization strategies based on Ca/P ion release still have some drawbacks, such as being time-consuming, having a spatiotemporal mismatch, and having limited intrafibrillar minerals. To tackle these problems, a prebonding rapid intrafibrillar mineralization strategy was developed in the present study. Specifically, polyacrylic acid–stabilized amorphous calcium fluoride (PAA-ACF) was found to induce rapid intrafibrillar mineralization of the single-layer collagen model and dentin collagen at just 1 min and 10 min, as identified by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. This strategy has also been identified to strengthen the mechanical properties of demineralized dentin within a clinically acceptable timeframe. Significantly, the bonding strength of the PAA-ACF–treated groups outperformed the control group irrespective of aging modes. In addition, the endogenous matrix metalloproteinases as well as exogenous bacterial erosion were inhibited, thus reducing the degradation of dentin collagen. High-quality integration of the hybrid layer and the underlying dentin was also demonstrated. On the basis of the present results, the concept of “prebonding rapid intrafibrillar mineralization” was proposed. This user-friendly scheme introduced PAA-ACF–based intrafibrillar mineralization into dentin bonding for the first time. As multifunctional primers, PAA-ACF precursors have the potential to shed new light on prolonging the service life of adhesive restorations, with promising significance.