3D printing calcium phosphate ceramics with high osteoinductivity through pore architecture optimization.

The osteoinductivity of 3D printed calcium phosphate (CaP) ceramics has a large gap compared with those prepared by conventional foaming methods, and improving the osteoinductivity of 3D printing CaP ceramics is crucial for successful application in bone regeneration. Pore architecture plays a critical role in osteoinductivity. In this study, CaP ceramics with a hexagonal close-packed (HCP) spherical pore structure were successfully fabricated using DLP printing technology. Additionally, octahedral (Octahedral), diamond (Diamond), and helical (Gyroid) structures were constructed with similar porosity and macropore diameter. CaP ceramics with the HCP structure exhibited higher compression strength (8.39 ± 1.82 MPa) and lower permeability (6.41 × 10-11 m2) compared to the Octahedral, Diamond, and Gyroid structures. In vitro cellular responses indicated that the macropore architecture strongly influenced the local growth rate of osteoblast-formed cell tissue; cells grew uniformly and formed circular rings in the HCP group. Furthermore, the HCP group promoted the expression of osteogenic genes and proteins more effectively than the other three groups. The outstanding osteoinductivity of the HCP group was confirmed in canine intramuscular implantation studies, where the new bone area reached up to 8.02 ± 1.94 % after a 10-week implantation. Additionally, the HCP group showed effective bone regeneration in repairing femoral condyle defects. Therefore, our findings suggest that 3D printed CaP bioceramics with an HCP structure promote osteoinductivity and can be considered as candidates for personalized precise treatment of bone defects in clinical applications. STATEMENT OF SIGNIFICANCE: 1. 3D printing BCP ceramics with high osteoinductivity were constructed through pore architecture optimization. 2. BCP ceramics with HCP structure exhibited relatively higher mechanical strength and lower permeability than those with Octahedral, Diamond and Gyroid structures. 3. BCP ceramics with HCP structure could promote the osteogenic differentiation of MC3T3-E1, and showed the superior in-vivo osteoinductivity and bone regeneration comparing with the other structures.

Mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nanoplatform for promoting bone regeneration.

Simultaneously modulating the inflammatory microenvironment and promoting local bone regeneration is one of the main challenges in treating bone defects. In recent years, osteoimmunology has revealed that the immune system plays an essential regulatory role in bone regeneration and that macrophages are critical components. In this work, a mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nano platform (Gold/hydroxyapatite nanocomposites functionalized with polydopamine - PDA@Au-HA) is developed to accelerate bone tissues regeneration by regulating the immune microenvironment. PDA coating endows nanomaterials with the ability to scavenge reactive oxygen species (ROS) and anti-inflammatory properties, and it also exhibits an immunomodulatory ability to inhibit M1 macrophage polarization and activate M2 macrophage secretion of osteogenesis-related cytokines. Most importantly, this nano platform promotes the polarization of M2 macrophages and regulates the crosstalk between macrophages and pre-osteoblast cells to achieve bone regeneration. Au-HA can synergistically promote vascularized bone regeneration through sustained release of Ca and P particles and gold nanoparticles (NPs). This nano platform has a synergistic effect of good compatibility, scavenging of ROS, and anti-inflammatory and immunomodulatory capability to accelerate the bone repair process. Thus, our research offers a possible therapeutic approach by exploring PDA@Au-HA nanocomposites as a bifunctional platform for tissue regeneration.

Characterization of an advanced bone graft material with a nanocrystalline hydroxycarbanoapatite surface and dual phase composition.

The bone formation response of ceramic bone graft materials can be improved by modifying the material's surface and composition. A unique dual-phase ceramic bone graft material with a nanocrystalline, hydroxycarbanoapatite (HCA) surface and a calcium carbonate core (TrelCor®-Biogennix, Irvine, CA) was characterized through a variety of analytical methods. Scanning electron microscopy (SEM) of the TrelCor surface (magnification 100-100,000X) clearly demonstrated a nanosized crystalline structure covering the entire surface. The surface morphology showed a hierarchical structure that included micron-sized spherulites fully covered by plate-like nanocrystals (<60 nm in thickness). Chemical and physical characterization of the material using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy Energy Dispersive X-ray Spectroscopy (SEM-EDX) showed a surface composed of HCA. Analysis of fractured samples confirmed the dual-phase composition with the presence of a calcium carbonate core and HCA surface. An in vitro bioactivity study was conducted to evaluate whether TrelCor would form a bioactive layer when immersed in simulated body fluid. This response was compared to a known bioactive material (45S5 bioactive glass - Bioglass). Following 14-days of immersion, surface and cross-sectional analysis via SEM-EDX showed that the TrelCor material elicited a bioactive response with the formation of a bioactive layer that was qualitatively thicker than the layer that formed on Bioglass. An in vivo sheep muscle pouch model was also conducted to evaluate the ability of the material to stimulate an ectopic, cellular bone formation response. Results were compared against Bioglass and a first-generation calcium phosphate ceramic that lacked a nanocrystalline surface. Histology and histomorphometric analysis (HMA) confirmed that the TrelCor nanocrystalline HCA surface stimulated a bone formation response in muscle (avg. 11% bone area) that was significantly greater than Bioglass (3%) and the smooth surface calcium phosphate ceramic (0%).

Injectable Nanocomposite Hydrogels with Strong Antibacterial, Osteoinductive, and ROS-Scavenging Capabilities for Periodontitis Treatment.

Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, Ti3C2Tx MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of Porphyromonas gingivalis, scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.

Mechanistic insights into the spontaneous induction of bone formation.

The grand discovery of morphogens, or "form-generating substances", revealed that tissue morphogenesis is initiated by soluble molecular signals or morphogens primarily belonging to the transforming growth factor-ß (TGF-ß) supergene family. The regenerative potential of bone rests on its extracellular matrix, which is the repository of several morphogens that tightly control cellular differentiating pathways, cellular matrix deposition and remodeling. Alluringly, the matrix also contains specific factors transferred from the heterotopic implanted bone matrices initiating "Tissue Induction", as provocatively described in Nature in 1945. Later, it was found that selected genes and gene products of the TGF-ß supergene family singly, synchronously, and synergistically mastermind the induction of bone formation. This review describes the phenomenon of the spontaneous and/or intrinsic osteoinductivity of calcium phosphate-based biomaterials and titanium' constructs without the applications of soluble osteogenetic molecular signals. The review shows the spontaneous induction of bone formation initiated by Ca++ activating stem cell differentiation and up-regulation of bone morphogenetic proteins genes. Expressed gene products are embedded into the concavities of the calcium phosphate-based substrata, initiating bone formation as a secondary response. Pure titanium's substrata do not initiate the spontaneous induction of bone formation. The induction of bone is solely dependent on acid, alkali and heat treatments to form apatite layers on the treated titanium surfaces. The induction of bone formation is achieved exclusively by apatite-based biomaterial surfaces. The hydroxyapatite, in its various forms and geometric configurations, finely tunes the induction of bone formation in heterotopic sites. Cellular differentiation by fine-tuning of the cellular molecular machinery is initiated by specific geometric modularity of the hydroxyapatite substrata that push cellular buttons that start the ripple-like cascade of "Tissue Induction", generating newly formed ossicles with bone marrow in heterotopic extraskeletal sites. The highlighted mechanistic insights into the spontaneous induction of bone formation are a research platform invocating selected molecular elements to construct the induction of bone formation.

Honeycomb-inspired ZIF-sealed interface enhances osseointegration via anti-infection and osteoimmunomodulation.

Implant-associated infections (IAIs) pose a significant threat to orthopedic surgeries. Bacteria colonizing the surface of implants disrupt bone formation-related cells and interfere with the osteoimmune system, resulting in an impaired immune microenvironment and osteogenesis disorders. Inspired by nature, a zeolitic imidazolate framework (ZIF)-sealed smart drug delivery system on Ti substrates (ZSTG) was developed for the "natural-artificial dual-enzyme intervention (NADEI)" strategy to address these challenges. The subtle sealing design of ZIF-8 on the TiO2 nanotubes ensured glucose oxidase (GOx) activity and prevented its premature leakage. In the acidic infection microenvironment, the degradation of ZIF-8 triggered the rapid release of GOx, which converted glucose into H2O2 for disinfection. The Zn2+ released from degraded ZIF-8, as a DNase mimic, can hydrolyze extracellular DNA, which further enhances H2O2-induced disinfection and prevents biofilm formation. Importantly, Zn2+-mediated M2 macrophage polarization significantly improved the impaired osteoimmune microenvironment, accelerating bone repair. Transcriptomics revealed that ZSTG effectively suppressed the inflammatory cascade induced by lipopolysaccharide while promoting cell proliferation, homeostasis maintenance, and bone repair. In vitro and in vivo results confirmed the superior anti-infective, osteoimmunomodulatory, and osteointegrative capacities of the ZSTG-mediated NADEI strategy. Overall, this smart bionic platform has significant potential for future clinical applications to treat IAIs.

Evaluation of In Vivo Biocompatibility in Preclinical Studies of a Finger Implant Medical Device Correlated with Mechanical Properties and Microstructure.

The aim of the experiment was to evaluate the biocompatibility of four 3D-printed biomaterials planned for use in the surgical treatment of finger amputees: Ti-6Al-4 V (Ti64), ZrO2-Al2O3 ceramic material (ATZ20), and osteoconductive (anodized Ti64) and antibacterial (Hydroxyapatite, HAp) coatings that adhere well to materials dedicated to finger bone implants. The work concerns the correlation of mechanical, microstructural, and biological properties of dedicated materials. Biological tests consisted of determining the overall cytotoxicity of the organism on the basis of in vivo tests carried out in accordance with the ISO 10993-6 and ISO 10993-11 standards. Clinical observations followed by diagnostic examinations, histopathological evaluation, and biochemical characterization showed no significant differences between control and tested groups of animals. The wound healed without complication, and no pathological effects were found. The wear test showed the fragility of the hydroxyapatite thin layer and the mechanical stability of the zirconia-based ceramic substrate. Electron microscopy observations revealed the layered structure of tested substrates and coatings.

Biological Evaluation of the Osteoinductive Potential of Dry Teeth after Chemical Demineralization Treatment Using the Tooth Transformer Device.

Several studies have already demonstrated the biocompatibility of a tooth as a grafting material in the regeneration of bone tissue, showing its osteoconductive potential, while no studies have verified whether the osteoinductive potential of a tooth remains constant or is altered after its treatment with the Tooth Transformer (TT) device. The aim of the study was to demonstrate that the treatment with the TT device did not alter the osteoinductivity of an extracted tooth that was stored dry. Twelve extracted human teeth were collected from real patients. Caries, tartar and filling materials were removed from each tooth; each tooth was coarsely cut and stored at room temperature (RT) until use. Each sample was shredded, demineralized and disinfected, using the TT device. Protein extraction was carried out for each sample, and Western Blot analysis was performed to test the presence of mineralization protein LIM-1 and transforming growth factor-ß. The presence of the human Bone Morphogenetic Protein 2 (BMP-2) and human collagen Type I (COL-I) was found in dry tooth samples processed with the TT device and subjected to Enzyme-Linked Immunosorbent Assay (ELISA) testing. The treatment of chemical demineralization using the TT device does not alter the osteoinductive potential of a dry tooth.

Crystalline Micro-Sized Carbonated Apatites: Chemical Anisotropy of the Crystallite Surfaces, Biocompatibility, Osteoconductivity, and Osteoinductive Effect Enhanced by Poly(ethylene phosphoric acid).

Carbonated hydroxyapatites (CAp) are very close to natural bone apatite in chemical composition and are regarded as a prospective bone mineral substitute for bone surgery and orthopedics. However, until now, the studies and applications of CAp were limited because of the amorphous nature of the synthetic CAp. In the present work, microsized highly crystalline carbonated apatites with uniform hexagonal (hCAp) or platelike (pCAp) morphology have been studied for the first time in vitro and in vivo, comparing against commercial hydroxyapatite (HAp) and ß-tricalcuim phosphate (ßTCP). In vitro experiments on dissolution of those calcium phosphate ceramics (CPCs) in acetate (pH 5.5) and Tris (pH 7.3) buffer solutions showed the following rank order of the dissolution rates: ßTCP > hCAp > pCAp > HAp. The higher dissolution rate of hCAp in comparison with pCAp is explained by chemical anisotropy of the crystallite surfaces, which was proven by SEM studies of the changes in the morphology of hCAp and pCAp crystallites during hydrolysis. A 5-week experiment on subcutaneous implantation of CPC species showed the following rank order of bioresorption rates: ßTCP > pCAp > hCAp > HAp. pCAp matrixes exhibited the highest biocompatibility, confirmed by histomorphological analysis. Three-month bone regeneration experiments involving a rat tibial defect model were conducted with 250-500 µm granules of pCAp and pCAp-PEPA [pCAp, pretreated with 2 wt % poly(ethylene phosphoric acid)]. Notably, pCAp-PEPA implants were resorbed at higher rates and induced the formation of more mature osseous tissue, a compact bone with Haversian systems.

Simulation of Cortical and Cancellous Bone to Accelerate Tissue Regeneration.

Different tissues have complex anisotropic structures to support biological functions. Mimicking these complex structures in vitro remains a challenge in biomaterials designs in support of tissue regeneration. Here, inspired by different types of silk nanofibers, a composite materials strategy was pursued towards this challenge. A combination of fabrication methods was utilized to achieve separate control of amorphous and beta-sheet rich silk nanofibers in the same solution. Aqueous solutions containing these two structural types of silk nanofibers were then simultaneously treated with an electric field and with ethylene glycol diglycidyl ether (EGDE). Under these conditions, the beta-sheet rich silk nanofibers in the mixture responded to the electric field while the amorphous nanofibers were active in the crosslinking process with the EGDE. As a result, cryogels with anisotropic structures were prepared, including mimics for cortical- and cancellous-like bone biomaterials as a complex osteoinductive niche. In vitro studies revealed that mechanical cues of the cryogels induced osteodifferentiation of stem cells while the anisotropy inside the cryogels influenced immune reactions of macrophages. These bioactive cryogels also stimulated improved bone regeneration in vivo through modulation of inflammation, angiogenesis and osteogenesis responses, suggesting an effective strategy to develop bioactive matrices with complex anisotropic structures beneficial to tissue regeneration.

Functionalization of Octacalcium Phosphate Bone Graft with Cisplatin and Zoledronic Acid: Physicochemical and Bioactive Properties.

Bones are the fourth most frequent site of metastasis from malignant tumors, including breast cancer, prostate cancer, melanoma, etc. The bioavailability of bone tissue for chemotherapy drugs is extremely low. This requires a search for new approaches of targeted drug delivery to the tumor growth zone after surgery treatment. The aim of this work was to develop a method for octacalcium phosphate (OCP) bone graft functionalization with the cytostatic drug cisplatin to provide the local release of its therapeutic concentrations into the bone defect. OCP porous ceramic granules (OCP ceramics) were used as a platform for functionalization, and bisphosphonate zoledronic acid was used to mediate the interaction between cisplatin and OCP and enhance their binding strength. The obtained OCP materials were studied using scanning electron and light microscopy, high-performance liquid chromatography, atomic emission spectroscopy, and real-time PCR. In vitro and in vivo studies were performed on normal and tumor cell lines and small laboratory animals. The bioactivity of initial OCP ceramics was explored and the efficiency of OCP functionalization with cisplatin, zoledronic acid, and their combination was evaluated. The kinetics of drug release and changes in ceramics properties after functionalization were studied. It was established that zoledronic acid changed the physicochemical and bioactive properties of OCP ceramics and prolonged cisplatin release from the ceramics. In vitro and in vivo experiments confirmed the biocompatibility, osteoconductivity, and osteoinductivity, as well as cytostatic and antitumor properties of the obtained materials. The use of OCP ceramics functionalized with a cytostatic via the described method seems to be promising in clinics when primary or metastatic tumors of the bone tissue are removed.

Bioactive impact of manuka honey and bone char incorporated into gelatin and chitosan cryogels in a rat calvarial fracture model.

Bone tissue engineered scaffolds are designed to mimic the natural environment for regeneration when typical healing is inhibited. Autografts are the current gold standard for treatment but are limited by available bone and supplementary surgical sites that broaden complications and comorbidities. Cryogels are an ideal scaffold in bone regeneration due to their mechanical integrity and marcoporous structure that elicits angiogenesis and subsequently new bone tissue formation. To aid in bioactivity and osteoinductivity, manuka honey (MH) and bone char (BC) were added to gelatin and chitosan cryogels (CG). Manuka honey has powerful antimicrobial properties to aid against graft infection, and bone char is composed of 90% hydroxyapatite, a well-studied bioactive material. These additives are natural, abundant, easy to use, and cost effective. CG cryogels incorporated with either BC or MH, and plain CG cryogels were implanted into rat calvarial fracture models for cortical bone regeneration analysis. We found indication of bioactivity with both bone char and manuka honey through the presence of woven bone structure in histology stains and micro computed tomography (microCT) data. Overall, plain CG cryogels supported greater bone regeneration capabilities than the BC or MH incorporated cryogels due to a lack of advanced organized tissue formation and collagen deposition after 8 weeks of implantation; however, future work should explore varying additive concentrations and delivery methods to further assess additive potential.

Strategies of strengthening mechanical properties in the osteoinductive calcium phosphate bioceramics.

Calcium phosphate (CaP) bioceramics are widely applied in the bone repairing field attributing to their excellent biological properties, especially osteoinductivity. However, their applications in load-bearing or segmental bone defects are severely restricted by the poor mechanical properties. It is generally considered that it is challenging to improve mechanical and biological properties of CaP bioceramics simultaneously. Up to now, various strategies have been developed to enhance mechanical strengths of CaP ceramics, the achievements in recent researches need to be urgently summarized. In this review, the effective and current means of enhancing mechanical properties of CaP ceramics were comprehensively summarized from the perspectives of fine-grain strengthening, second phase strengthening, and sintering process optimization. What's more, the further improvement of mechanical properties for CaP ceramics was prospectively proposed including heat treatment and biomimetic. Therefore, this review put forward the direction about how to compatibly improve mechanical properties of CaP ceramics, which can provide data and ideas for expanding the range of their clinical applications.

Physiologic Response Evaluation of Human Foetal Osteoblast Cells within Engineered 3D-Printed Polylactic Acid Scaffolds.

Large bone defect treatments have always been one of the important challenges in clinical practice and created a huge demand for more efficacious regenerative approaches. The bone tissue engineering (BTE) approach offered a new alternative to conventional bone grafts, addressing all clinical needs. Over the past years, BTE research is focused on the study and realisation of new biomaterials, including 3D-printed supports to improve mechanical, structural and biological properties. Among these, polylactic acid (PLA) scaffolds have been considered the most promising biomaterials due to their good biocompatibility, non-toxic biodegradability and bioresorbability. In this work, we evaluated the physiological response of human foetal osteoblast cells (hFOB), in terms of cell proliferation and osteogenic differentiation, within oxygen plasma treated 3D-printed PLA scaffolds, obtained by fused deposition modelling (FDM). A mechanical simulation to predict their behaviour to traction, flexural or torque solicitations was performed. We found that: 1. hFOB cells adhere and grow on scaffold surfaces; 2. hFOB grown on oxygen plasma treated PLA scaffolds (PLA_PT) show an improvement of cell adhesion and proliferation, compared to not-plasma treated scaffolds (PLA_NT); 3. Over time, hFOB penetrate along strands, differentiate, and form a fibrous matrix, tissue-like; 4. 3D-printed PLA scaffolds have good mechanical behaviour in each analysed configuration. These findings suggest that 3D-printed PLA scaffolds could represent promising biomaterials for medical implantable devices in the orthopaedic field.

Calcium-to-phosphorus releasing ratio affects osteoinductivity and osteoconductivity of calcium phosphate bioceramics in bone tissue engineering.

Calcium phosphate (Ca-P) bioceramics, including hydroxyapatite (HA), biphasic calcium phosphate (BCP), and beta-tricalcium phosphate (ß-TCP), have been widely used in bone reconstruction. Many studies have focused on the osteoconductivity or osteoinductivity of Ca-P bioceramics, but the association between osteoconductivity and osteoinductivity is not well understood. In our study, the osteoconductivity of HA, BCP, and ß-TCP was investigated based on the osteoblastic differentiation in vitro and in situ as well as calvarial defect repair in vivo, and osteoinductivity was evaluated by using pluripotent mesenchymal stem cells (MSCs) in vitro and heterotopic ossification in muscles in vivo. Our results showed that the cell viability, alkaline phosphatase activity, and expression of osteogenesis-related genes, including osteocalcin (Ocn), bone sialoprotein (Bsp), alpha-1 type I collagen (Col1a1), and runt-related transcription factor 2 (Runx2), of osteoblasts each ranked as BCP > ß-TCP > HA, but the alkaline phosphatase activity and expression of osteogenic differentiation genes of MSCs each ranked as ß-TCP > BCP > HA. Calvarial defect implantation of Ca-P bioceramics ranked as BCP > ß-TCP ≥ HA, but intramuscular implantation ranked as ß-TCP ≥ BCP > HA in vivo. Further investigation indicated that osteoconductivity and osteoinductivity are affected by the Ca/P ratio surrounding the Ca-P bioceramics. Thus, manipulating the appropriate calcium-to-phosphorus releasing ratio is a critical factor for determining the osteoinductivity of Ca-P bioceramics in bone tissue engineering.

The Localized Ionic Microenvironment in Bone Modelling/Remodelling: A Potential Guide for the Design of Biomaterials for Bone Tissue Engineering.

Bone is capable of adjusting size, shape, and quality to maintain its strength, toughness, and stiffness and to meet different needs of the body through continuous remodeling. The balance of bone homeostasis is orchestrated by interactions among different types of cells (mainly osteoblasts and osteoclasts), extracellular matrix, the surrounding biological milieus, and waste products from cell metabolisms. Inorganic ions liberated into the localized microenvironment during bone matrix degradation not only form apatite crystals as components or enter blood circulation to meet other bodily needs but also alter cellular activities as molecular modulators. The osteoinductive potential of inorganic motifs of bone has been gradually understood since the last century. Still, few have considered the naturally generated ionic microenvironment's biological roles in bone remodeling. It is believed that a better understanding of the naturally balanced ionic microenvironment during bone remodeling can facilitate future biomaterial design for bone tissue engineering in terms of the modulatory roles of the ionic environment in the regenerative process.

Continuously released Zn2+ in 3D-printed PLGA/ß-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties.

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment. Artificial bone graft materials such as Poly (lactic-co-glycolic acid)/ß-tricalcium phosphate (PLGA/ß-TCP) scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity. However, insufficient mechanical properties, lack of osteoinductivity and infections after implanted limit its large-scale clinical application. Hence, we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/ß-TCP using low temperature rapid prototyping 3D printing technology. We first screened the scaffolds with 1 wt% Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity. As designed, the scaffold had a multi-level porous structure of biomimetic cancellous bone, and the Young's modulus (63.41 ± 1.89 MPa) and compressive strength (2.887 ± 0.025 MPa) of the scaffold were close to those of cancellous bone. In addition, after a series of in vitro and in vivo experiments, the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation, as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/ß-TCP scaffold without zinc particles. We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/ß-catenin, P38 MAPK and NFkB pathways. This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials. We envision that this scaffold may become a new strategy for clinical treatment of bone defects.

Calcium Phosphate Bone Cements Incorporated with Black Phosphorus Nanosheets Enhanced Osteogenesis.

For decades, calcium phosphate bone cements (CPCs) showed impressive advantages for their good biocompatibility, injectability, and osteoconductivity in the bone repair field. However, it is still difficult to prepare CPCs with outstanding antibacterial and self-curing properties, sufficient phosphorus release, and osteoinductivity for clinical application. Herein, we used partially crystallized calcium phosphate and dicalcium phosphate anhydrate particles incorporated with black phosphorous nanosheets to prepare calcium phosphate bone cements (CPCs). The curing time, compressive strength, photothermal properties, and degradation performance of BP/CPC were investigated. In addition, the cytocompatibility and osteoinductivity of BP/CPC were evaluated by cell adhesion, cytotoxicity, alkaline phosphatase detection, alizarin red staining, and western blot assay. The results indicated that BP/CPC showed adjustable curing time, good cytocompatibility, outstanding photothermal properties, and osteoinductivity, suggesting their potential application for bone regeneration.

A review on design of scaffold for osteoinduction: Toward the unification of independent design variables.

Biophysical stimulus quantifies the osteoinductivity of the scaffold concerning the mechanoregulatory mathematical models of scaffold-assisted cellular differentiation. Consider a set of independent structural variables ($) that comprises bulk porosity levels ([Formula: see text]) and a set of morphological features of the micro-structure ([Formula: see text]) associated with scaffolds, i.e., [Formula: see text]. The literature suggests that biophysical stimulus ([Formula: see text]) is a function of independent structural variables ($). Limited understanding of the functional correlation between biophysical stimulus and structural features results in the lack of the desired osteoinductivity in a scaffold. Consequently, it limits their broad applicability to assist bone tissue regeneration for treating critical-sized bone fractures. The literature indicates the existence of multi-dimensional independent design variable space as a probable reason for the general lack of osteoinductivity in scaffolds. For instance, known morphological features are the size, shape, orientation, continuity, and connectivity of the porous regions in the scaffold. It implies that the number of independent variables ([Formula: see text]) is more than two, i.e., [Formula: see text], which interact and influence the magnitude of [Formula: see text] in a unified manner. The efficiency of standard engineering design procedures to analyze the correlation between dependent variable ([Formula: see text]) and independent variables ($) in 3D mutually orthogonal Cartesian coordinate system diminishes proportionally with the increase in the number of independent variables ([Formula: see text]) (Deb in Optimization for engineering design-algorithms and examples, PHI Learning Private Limited, New Delhi, 2012). Therefore, there is an immediate need to devise a framework that has the potential to quantify the micro-structural's morphological features in a unified manner to increase the prospects of scaffold-assisted bone tissue regeneration.

Current strategies for enhancement of the bioactivity of artificial ligaments: A mini-review.

Background and objective: Anterior cruciate ligament (ACL) reconstruction calls for artificial ligaments with better bioactivity, however systematic reviews regarding bioactivity enhancement strategies, technologies, and perspectives of artificial ligaments have been rarely found. Methods: Research papers, reviews, and clinical reports related to artificial ligaments were searched and summarized the current status and research trends of artificial ligaments through a systematic analysis. Results: Having experienced ups and downs since the very first record of clinical application, artificial ligaments differing in material, and fabrication methods have been reported with different clinical performances. Various manufacturing technologies have developed and realized scaffold- and cell-based strategies. Despite encouraging in-vivo and in-vitro test results, the clinical results of such new designs need further clinical examinations. Conclusion: As the demand for ACL reconstruction dramatically increases, novel artificial ligaments with better osteoinductivity and mechanical performance are promising. The translational potential of this article: To develop novel artificial ligaments simultaneously possessing excellent osteoinductivity and satisfactory mechanical performance, it is important to grab a glance at recent research advances. This systematic analysis provides researchers and clinicians with comprehensive and comparable information on artificial ligaments, thus being of clinical translational significance.