Redefined ion association constants have consequences for calcium phosphate nucleation and biomineralization.

Calcium orthophosphates (CaPs), as hydroxyapatite (HAP) in bones and teeth are the most important biomineral for humankind. While clusters in CaP nucleation have long been known, their speciation and mechanistic pathways to HAP remain debated. Evidently, mineral nucleation begins with two ions interacting in solution, fundamentally underlying solute clustering. Here, we explore CaP ion association using potentiometric methods and computer simulations. Our results agree with literature association constants for Ca2+ and H2PO4-, and Ca2+ and HPO42-, but not for Ca2+ and PO43- ions, which previously has been strongly overestimated by two orders of magnitude. Our data suggests that the discrepancy is due to a subtle, premature phase separation that can occur at low ion activity products, especially at higher pH. We provide an important revision of long used literature constants, where association of Ca2+ and PO43- actually becomes negligible below pH 9.0, in contrast to previous values. Instead, [CaHPO4]0 dominates the aqueous CaP speciation between pH ~6-10. Consequently, calcium hydrogen phosphate association is critical in cluster-based precipitation in the near-neutral pH regime, e.g., in biomineralization. The revised thermodynamics reveal significant and thus far unexplored multi-anion association in computer simulations, constituting a kinetic trap that further complicates aqueous calcium phosphate speciation.

Porous Nano-Fiber Structure of Modified Electrospun Chitosan GBR Membranes Improve Osteoblast Calcium Phosphate Deposition in Osteoblast-Fibroblast Co-Cultures.

Desirable characteristics of electrospun chitosan membranes (ESCM) for guided bone regeneration are their nanofiber structure that mimics the extracellular fiber matrix and porosity for the exchange of signals between bone and soft tissue compartments. However, ESCM are susceptible to swelling and loss of nanofiber and porous structure in physiological environments. A novel post-electrospinning method using di-tert-butyl dicarbonate (tBOC) prevents swelling and loss of nanofibrous structure better than sodium carbonate treatments. This study aimed to evaluate the hypothesis that retention of nanofiber morphology and high porosity of tBOC-modified ESCM (tBOC-ESCM) would support more bone mineralization in osteoblast-fibroblast co-cultures compared to Na2CO3 treated membranes (Na2CO3-ESCM) and solution-cast chitosan solid films (CM-film). The results showed that only the tBOC-ESCM retained the nanofibrous structure and had approximately 14 times more pore volume than Na2CO3-ESCM and thousands of times more pore volume than CM-films, respectively. In co-cultures, the tBOC-ESCM resulted in a significantly greater calcium-phosphate deposition by osteoblasts than either the Na2CO3-ESCM or CM-film (p < 0.05). This work supports the study hypothesis that tBOC-ESCM with nanofiber structure and high porosity promotes the exchange of signals between osteoblasts and fibroblasts, leading to improved mineralization in vitro and thus potentially improved bone healing and regeneration in guided bone regeneration applications.

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.

Do Implant Coatings Affect Healing of Placed Implants? An Umbrella Review.

PURPOSE: To analyze the available evidence and assess the effect of different implant coatings on healing outcomes. MATERIALS AND METHODS: Using the PICOS strategy, a structured question was formed. A protocol was agreed upon and registered with PROSPERO (no. CRD42022321926). The MEDLINE, Embase, Cochrane Database of Systematic Reviews, Scopus, Web of Science, Pubmed, and ScienceDirect databases were searched using a structured strategy. Study selection was independently carried out in duplicate, first by title and abstract, then by full-text assessment. Quality and risk of bias were independently assessed in duplicate using AMSTAR 2 and ROBIS. Data extraction was independently undertaken in duplicate using a predefined extraction form. RESULTS: The search yielded 11 systematic reviews for inclusion. The most commonly assessed coatings were based on calcium phosphate-including hydroxyapatite (HA), brushite, and bioabsorbable nano-HA-followed by bisphosphonate, then bioactive glass coatings. Included reviews most frequently assessed marginal bone loss (MBL), bone-to-implant contact (BIC), and survival/success rates. There was considerable heterogeneity and small sample sizes. The quality assessment suggested low confidence in the reviews and high risk of bias. CONCLUSIONS: The included reviews provide weak evidence that implant coatings improve osseointegration and reduce MBL following implant placement. There was weak evidence for progressive complications for calcium phosphate coatings. Further research and long-term multicenter controlled clinical trials with improved standardization and control of bias are required to better understand the effects of coating implants.

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Evolution and diversity of biomineralized columnar architecture in early Cambrian phosphatic-shelled brachiopods.

Biologically-controlled mineralization producing organic-inorganic composites (hard skeletons) by metazoan biomineralizers has been an evolutionary innovation since the earliest Cambrian. Among them, linguliform brachiopods are one of the key invertebrates that secrete calcium phosphate minerals to build their shells. One of the most distinct shell structures is the organo-phosphatic cylindrical column exclusive to phosphatic-shelled brachiopods, including both crown and stem groups. However, the complexity, diversity, and biomineralization processes of these microscopic columns are far from clear in brachiopod ancestors. Here, exquisitely well-preserved columnar shell ultrastructures are reported for the first time in the earliest eoobolids Latusobolus xiaoyangbaensis gen. et sp. nov. and Eoobolus acutulus sp. nov. from the Cambrian Series 2 Shuijingtuo Formation of South China. The hierarchical shell architectures, epithelial cell moulds, and the shape and size of cylindrical columns are scrutinised in these new species. Their calcium phosphate-based biomineralized shells are mainly composed of stacked sandwich columnar units. The secretion and construction of the stacked sandwich model of columnar architecture, which played a significant role in the evolution of linguliforms, is highly biologically controlled and organic-matrix mediated. Furthermore, a continuous transformation of anatomic features resulting from the growth of diverse columnar shells is revealed between Eoobolidae, Lingulellotretidae, and Acrotretida, shedding new light on the evolutionary growth and adaptive innovation of biomineralized columnar architecture among early phosphatic-shelled brachiopods during the Cambrian explosion.

Injectable macroporous naturally-derived apatite bone cement as a potential trabecular bone substitute.

In this study, we have formulated a novel apatite bone cements derived from natural sources (i.e. eggshell and fishbone) with improved qualities that is, porosity, resorbability, biological activity, and so forth. The naturally-derived apatite bone cement (i.e. FBDEAp) was prepared by mixing hydroxyapatite (synthesized from fishbone) and tricalcium phosphate (synthesized from eggshell) as a solid phase with a liquid phase (a dilute acidic blend of cement binding accelerator and biopolymers like gelatin and chitosan) with polysorbate (as liquid porogen) to get a desired bone cement paste. The prepared cement paste sets within the clinically acceptable setting time (≤20 min), easily injectable (>85%) through hands and exhibits physiological pH stability (7.3-7.4). The pure apatite phased bone cement was confirmed by x-ray diffraction and Fourier transform infrared spectroscopy analyses. The FBDEAp bone cement possesses acceptable compressive strength (i.e. 5-7 MPa) within trabecular bone range and is resorbable up to 28% in simulated body fluid solution within 12 weeks of incubation at physiological conditions. The FBDEAp is macroporous in nature (average pore size ~50-400 µm) with interconnected pores verified by SEM and micro-CT analyses. The FBDEAp showed significantly increased MG63 cell viability (>125% after 72 h), cell adhesion, proliferation, and key osteogenic genes expression levels (up to 5-13 folds) compared to the synthetically derived, synthetic and eggshell derived as well as synthetic and fishbone derived bone cements. Thus, we strongly believe that our prepared FBDEAp bone cement can be used as potential trabecular bone substitute in orthopedics.

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 SIGNIFICANCE: Collagen 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.

Branched Channels in Porous ß-Tricalcium Phosphate Scaffold Promote Vascularization.

Rapid and efficient vascularization is still considerably challenging for a porous ß-tricalcium phosphate (ß-TCP) scaffold to achieve. To overcome this challenge, branched channels were created in the porous ß-TCP scaffold by using 3D printing and a template-casting method to facilitate the instant flow of blood supply. Human bone mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) were seeded in the channeled porous scaffolds and characterized through a double-stranded DNA (dsDNA) assay, alkaline phosphatase (ALP) assay, and cell migration. Channeled porous ß-TCP scaffolds were then implanted in the subcutaneous pockets of mice. Histological staining and immunohistochemical staining on vascularization and bone-related markers were carried out on the embedded paraffin sections. Results from in vitro experiments showed that branched channels significantly promoted HUVECs' infiltration, migration, proliferation, and angiogenesis, and also promoted the proliferation and osteogenesis differentiation of hBMSCs. In vivo implantation results showed that, in the early stage after implantation, cells significantly migrated into branched channeled scaffolds. More matured blood vessels formed in the branched channeled scaffolds compared to that in nonchanneled and straight channeled scaffolds. Beside promoting vascularization, the branched channels also stimulated the infiltration of bone-related cells into the scaffolds. These results suggested that the geometric design of branched channels in the porous ß-TCP scaffold promoted rapid vascularization and potentially stimulated bone cells recruitment.

Simultaneous Regulation of the Mechanical/Osteogenic Capacity of Brushite Calcium Phosphate Cement by Incorporating with Poly(ethylene glycol) Dicarboxylic Acid.

Brushite calcium phosphate cement (brushite CPC) is a prospective bone repair material due to its ideal resorption rates in vivo. However, the undesirable mechanical property and bioactivity limited its availability in clinic application. To address this issue, incorporating polymeric additives has emerged as a viable solution. In this study, poly(ethylene glycol) dicarboxylic acid, PEG(COOH), was synthesized and employed as the polymeric additive. The setting behavior, anti-washout ability, mechanical property, degradation rate, and osteogenic capacity of brushite CPC were regulated by incorporating PEG(COOH). The incorporation of PEG(COOH) with carboxylic acid groups demonstrated a positive effect on both mechanical properties and osteogenic activity in bone repair. This study offers valuable insights and suggests a promising strategy for the development of materials in bone tissue engineering.

Biocompatibility and Osseointegration of the Biomimetically Coated and Water-Soluble Eggshell Membrane Protein Cross-Linked Ti Alloy Screws.

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.

Remineralization potential of dentifrices with calcium sodium phosphosilicate and functionalized tri-calcium phosphate in the deeper incipient carious lesions: An in vitro study.

OBJECTIVES: This study evaluated the remineralization potential of calcium sodium phosphosilicate and functionalized tri-calcium phosphate (f-TCP) dentifrices in deeper incipient carious lesions (ICLs). MATERIALS AND METHODS: Artificial ICLs were created by placing premolars into demineralizing solutions. Teeth were randomly assigned into four groups: calcium sodium phosphosilicate (Group 1), f-TCP (Group 2), 1450 ppm fluoride (Group 3), and distilled water (Group 4), which were subjected to 10-day pH cycling. Mineral density (MD) was assessed using microcomputed tomography (Micro-CT), while hardness (H) and elastic modulus (EM) were assessed using nanomechanical testing. RESULTS: MD % gain was higher in Groups 1-3 than in Group 4. In addition, Groups 1 and 2 exhibited significantly higher MD % gain than Group 3. Also, Groups 1-3 showed significantly higher EM and H values than Group 4 in the outer enamel area; yet, Groups 1 and 2 displayed significantly higher EM and H values than Groups 3 and 4 in the inner enamel. CONCLUSIONS: The MD, EM, and H of ICLs significantly increased with the addition of calcium sodium phosphosilicate or f-TCP to fluoridated dentifrices compared to standard fluoride dentifrices. The added active ingredients remineralized the deeper parts of the ICLs, while remineralization at the lesion surface was similar between tested dentifrices.

Performance of microbial inoculation and tricalcium phosphate on nitrogen retention and conversion: Core microorganisms and enzyme activity during kitchen waste composting.

The substantial release of NH3 during composting leads to nitrogen (N) losses and poses environmental hazards. Additives can mitigate nitrogen loss by adsorbing NH3/NH4, adjusting pH, and enhancing nitrification, thereby improving compost quality. Herein, we assessed the effects of combining bacterial inoculants (BI) (1.5%) with tricalcium phosphate (CA) (2.5%) on N retention, organic N conversion, bacterial biomass, functional genes, network patterns, and enzyme activity during kitchen waste (KW) composting. Results revealed that adding of 1.5%/2.5% (BI + CA) significantly (p < 0.05) improved ecological parameters, including pH (7.82), electrical conductivity (3.49 mS/cm), and N retention during composting. The bacterial network properties of CA (265 node) and BI + CA (341 node) exhibited a substantial niche overlap compared to CK (210 node). Additionally, treatments increased organic N and total N (TN) content while reducing NH4+-N by 65.42% (CA) and 77.56% (BI + CA) compared to the control (33%). The treatments, particularly BI + CA, significantly (p < 0.05) increased amino acid N, hydrolyzable unknown N (HUN), and amide N, while amino sugar N decreased due to bacterial consumption. Network analysis revealed that the combination expanded the core bacterial nodes and edges involved in organic N transformation. Key genes facilitating nitrogen mediation included nitrate reductase (nasC and nirA), nitrogenase (nifK and nifD), and hydroxylamine oxidase (hao). The structural equation model suggested that combined application (CA) and microbial inoculants enhance enzyme activity and bacterial interactions during composting, thereby improving nitrogen conversion and increasing the nutrient content of compost products.

Synthesis of pure and doped nano-calcium phosphates using different conventional methods for biomedical applications: a review.

The applications of calcium phosphates (hydroxyapatite, tetracalcium phosphate, tricalcium phosphate (alpha and beta), fluorapatite, di-calcium phosphate anhydrous, and amorphous calcium-phosphate) are increasing day by day. Calcium hydroxyapatite, commonly known as hydroxyapatite (HAp), represents a mineral form of calcium apatite. Owing to its close molecular resemblance to the mineral constituents of bones, teeth, and hard tissues, HAp is often employed in the biomedical domain. In addition, it is extensively employed in various sectors such as the remediation of water, air, and soil pollution. The key advantage of HAp lies in its potential to accommodate a wide variety of anionic and cationic substitutions. Nevertheless, HAp and tricalcium phosphate (TCP) syntheses typically involve the use of chemical precursors containing calcium and phosphorus sources and employ diverse techniques, such as solid-state, wet, and thermal methods or a combination of these processes. Researchers are increasingly favoring natural sources such as bio-waste (eggshells, oyster shells, animal bones, fish scales, etc.) as viable options for synthesizing HAp. Interestingly, the synthesis route significantly influences the morphology, size, and crystalline phase of calcium phosphates. In this review paper, we highlight both dry and wet methods, which include six commonly used synthesis methods (i.e. solid-state, mechano-chemical, wet-chemical precipitation, hydrolysis, sol-gel, and hydrothermal methods) coupled with the variation in source materials and their influence in modifying the structural morphology from a bulky state to nanoscale to explore the applications of multifunctional calcium phosphates in different formats.

Synthesis and characterization of functional calcium-phosphate-chitosan adsorbents for fluoride removal from water.

Functional calcium-phosphate-chitosan adsorbents for fluoride (F-) removal from water with different proportions of calcium (0.7 or 1.4 % w/v) were synthesized by: i) ionotropic gelation technique followed by drying in a convection oven (IGA) or freeze drying (FDA); ii) freeze-gelation followed by drying in a convection oven (FGA). Adsorbents were analyzed by SEM-EDX and FTIR- ATR. F- removal percentages higher than 45 % were obtained with calcium-phosphate-chitosan adsorbents for an initial F- concentration of 9.6 mg L-1. Optimal conditions for F- removal were attained, using calcium-phosphate- chitosan adsorbents synthesized by ionotropic gelation with 0.7 % of Ca (IGA0.7). Under these conditions, initial F- concentration of 5 mg L-1, was reduced below the maximum limit of 1.5 mg L-1 established by WHO. Regeneration of IGA0.7 was achieved in acid media. The performance of IGA0.7 was slightly reduced in the presence of coexisting anions (nitrate, carbonate, arsenate). Adsorption kinetics was represented satisfactorily by the pseudo-second order equation; Langmuir isotherm provided the best fit to the equilibrium data and IGA0.7 exhibited a maximum F- adsorption capacity qL = 132.25 mg g-1. IGA0.7 particles were characterized by thermogravimetry coupled to FTIR, XRD, XPS and SEM-EDX. The calcium-phosphate-chitosan adsorbents constitute a suitable and emerging material for water defluorination.

Effects of vehicles on the physical properties and biocompatibility of premixed calcium silicate cements.

Premixed calcium silicate cements (pCSCs) contain vehicles which endow fluidity and viscosity to CSCs. This study aimed to investigate the effects of three vehicles, namely, polyethylene glycol (PEG), propylene glycol (PG), and dimethyl sulfoxide (DMSO), on the physicochemical properties and biocompatibility of pCSCs. The setting time, solubility, expansion rate, and mechanical strength of the pCSCs were evaluated, and the formation of calcium phosphate precipitates was assessed in phosphate-buffered saline (PBS). The effects of pCSC extracts on the osteogenic differentiation of mesenchymal stem cells (MSCs) were investigated. Finally, the tissue compatibility of pCSCs in rat femurs was observed. CSC containing PEG (CSC-PEG) exhibited higher solubility and setting time, and CSC-DMSO showed the highest expansion rate and mechanical strength. All pCSCs generated calcium phosphate precipitates. The extract of CSC-PG induced the highest expressions of osteogenic markers along with the greatest calcium deposites. When implanted in rat femurs, CSC-PEG was absorbed considerably, whereas CSC-PG remained relatively unaltered inside the femur.

Synergistic effects of calcium silicate/zinc silicate dual compounds andin-situinterconnected pores on promoting bone regeneration of composite scaffolds.

Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration.In vitroresults demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a great bone repair effect, as evidenced by more new bone formation and a faster scaffold biodegradation compared to the scaffold with CS alone.

Direct inkjet writing of polylactic acid/ß-tricalcium phosphate composites for bone tissue regeneration: A proof-of-concept study.

There is an ever-evolving need of customized, anatomic-specific grafting materials for bone regeneration. More specifically, biocompatible and osteoconductive materials, that may be configured dynamically to fit and fill defects, through the application of an external stimulus. The objective of this study was to establish a basis for the development of direct inkjet writing (DIW)-based shape memory polymer-ceramic composites for bone tissue regeneration applications and to establish material behavior under thermomechanical loading. Polymer-ceramic (polylactic acid [PLA]/ß-tricalcium phosphate [ß-TCP]) colloidal gels were prepared of different w/w ratios (90/10, 80/20, 70/30, 60/40, and 50/50) through polymer dissolution in acetone (15% w/v). Cytocompatibility was analyzed through Presto Blue assays. Rheological properties of the colloidal gels were measured to determine shear-thinning capabilities. Gels were then extruded through a custom-built DIW printer. Space filling constructs of the gels were printed and subjected to thermomechanical characterization to measure shape fixity (Rf) and shape recovery (Rr) ratios through five successive shape memory cycles. The polymer-ceramic composite gels exhibited shear-thinning capabilities for extrusion through a nozzle for DIW. A significant increase in cellular viability was observed with the addition of ß-TCP particles within the polymer matrix relative to pure PLA. Shape memory effect in the printed constructs was repeatable up to 4 cycles followed by permanent deformation. While further research on scaffold macro-/micro-geometries, and engineered porosities are warranted, this proof-of-concept study suggested suitability of this polymer-ceramic material and the DIW 3D printing workflow for the production of customized, patient specific constructs for bone tissue engineering.

Transpedicular injection of rhBMP-2 with ß-tricalcium phosphate to reduce the proximal junctional kyphosis after adult spinal deformity correction: preliminary study.

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.