In Situ-Sprayed Bioinspired Adhesive Conductive Hydrogels for Cavernous Nerve Repair.

Cavernous nerve injury (CNI), resulting in erectile dysfunction (ED), poses a significant threat to the quality of life for men. Strategies utilizing conductive hydrogels have demonstrated promising results for the treatment of peripheral nerves with a large diameter (>2 mm). However, integrating convenient minimally invasive operation, antiswelling and immunomodulatory conductive hydrogels for treating small-diameter injured cavernous nerves remains a great challenge. Here, a sprayable adhesive conductive hydrogel (GACM) composed of gelatin, adenine, carbon nanotubes, and mesaconate designed for cavernous nerve repair is developed. Multiple hydrogen bonds provide GACM with excellent adhesive and antiswelling properties, enabling it to establish a conformal electrical bridge with the damaged nerve and aiding in the regeneration process. Additionally, mesaconate-loaded GACM suppresses the release of inflammatory factors by macrophages and promotes the migration and proliferation of Schwann cells. In vivo tests demonstrate that the GACM hydrogel repairs the cavernous nerve and restores erectile function and fertility. Furthermore, the feasibility of sprayable GACM in minimally invasive robotic surgery in beagles is validated. Given the benefits of therapeutic effectiveness and clinical convenience, the research suggests a promising future for sprayable GACM materials as advanced solutions for minimally invasive nerve repair.

3D-Printed Flat-Bone-Mimetic Bioceramic Scaffolds for Cranial Restoration.

The limitations of autologous bone grafts necessitate the development of advanced biomimetic biomaterials for efficient cranial defect restoration. The cranial bones are typical flat bones with sandwich structures, consisting of a diploe in the middle region and 2 outer compact tables. In this study, we originally developed 2 types of flat-bone-mimetic ß-tricalcium phosphate bioceramic scaffolds (Gyr-Comp and Gyr-Tub) by high-precision vat-photopolymerization-based 3-dimensional printing. Both scaffolds had 2 outer layers and an inner layer with gyroid pores mimicking the diploe structure. The outer layers of Gyr-Comp scaffolds simulated the low porosity of outer tables, while those of Gyr-Tub scaffolds mimicked the tubular pore structure in the tables of flat bones. The Gyr-Comp and Gyr-Tub scaffolds possessed higher compressive strength and noticeably promoted in vitro cell proliferation, osteogenic differentiation, and angiogenic activities compared with conventional scaffolds with cross-hatch structures. After implantation into rabbit cranial defects for 12 weeks, Gyr-Tub achieved the best repairing effects by accelerating the generation of bone tissues and blood vessels. This work provides an advanced strategy to prepare biomimetic biomaterials that fit the structural and functional needs of efficacious bone regeneration.

Preparation of lithium-containing magnesium phosphate-based composite ceramics having high compressive strength, osteostimulation and proangiogenic effects.

Fairly high concentrations of magnesium and lithium are conducive to improving the osteogenic and angiogenic capacities. In the current study, lithium-containing magnesium phosphate-based ceramics (AMP/LMPGs) were prepared from amorphous magnesium phosphate (AMP) at a low sintering temperature (650 °C), and the lithium/magnesium-containing phosphate glasses (LMPGs) were utilized as sintering additives. During the sintering procedure of AMP/LMPGs, the AMP reacted with LMPGs, producing new compounds. The AMP/LMPGs displayed nano-size grains and plentiful micropores. The addition of LMPGs noticeably increased the porosity as well as compressive strength of the AMP/LMPGs ceramics. The AMP/LMPGs sustainedly released Mg, P and Li ions, forming Mg-rich ionic microenvironment, which ameliorated cellular proliferation, osteogenic differentiation and proangiogenic capacities. The AMP/LMPGs ceramics with considerably high compressive strength, osteostimulation and proangiogenic effects were expected to efficiently regenerate the bone defects.

Fabrication of 3D printed Ca3Mg3(PO4)4-based bioceramic scaffolds with tailorable high mechanical strength and osteostimulation effect.

Calcium, magnesium and phosphate are predominant constituents in the human bone. In this study, magnesium-calcium phosphate composite bioceramic scaffolds were fabricated utilizing Mg3(PO4)2 and ß-Ca3(PO4)2 as starting materials, and their pore structure was constructed by 3D printing. The porosity and compressive strength of the composite bioceramic scaffolds could be adjusted by altering the sintering temperature and the formula of starting materials. The composite bioceramic scaffolds prepared from 60 wt% Mg3(PO4)2 and 40 wt% ß-Ca3(PO4)2 were dominated by the Ca3Mg3(PO4)4 phase, and this Ca3Mg3(PO4)4-based bioceramic scaffolds possessed the highest compressive strength (12.7 - 92.4 MPa). Moreover, the Ca3Mg3(PO4)4-based bioceramic scaffolds stimulated cellular growth and osteoblastic differentiation of bone marrow stromal cells. The Ca3Mg3(PO4)4-based bioceramic scaffolds as bone regenerative biomaterials are flexible to the requirement of bone defects at various sites.

Enhanced osteogenesis and angiogenesis of biphasic calcium phosphate scaffold by synergistic effect of silk fibroin coating and zinc doping.

Biphasic calcium phosphate (BCP) scaffold has been widely applied to bone regeneration because of its good biocompatibility and bone conduction property. However, the low mechanical strength and the lack of angiogenic and osteogenic induction properties have restricted its application in bone tissue regeneration. In this study, we combined zinc (Zn2+) doping and silk fibroin (SF) coating with expectation to enhance compressive strength, osteogenesis and angiogenesis of BCP scaffolds. The phase composition, morphology, porosity, compressive strength, in vitro degradation and cell behaviors were investigated systematically. Results showed that the scaffold coated with SF exhibited almost 3 times of compressive strength without compromising its porosity compared with the uncoated scaffold. Zn2+ doping and SF coating synergistically enhanced the alkaline phosphatase activity and osteogenesis-related genes expression of mouse bone mesenchymal stem cells (mBMSCs). Furthermore, SF coating notably improved the proliferation, cell viability and in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). This work provides a novel way to modify BCP scaffolds simultaneously with enhancing mechanical strength and biological properties.

3D-plotted zinc silicate/ß-tricalcium phosphate ceramic scaffolds enable fast osteogenesis by activating the p38 signaling pathway.

Biomaterials in combination with multiple bioactive ions could create a favorable microenvironment for bone remolding. Herein, zinc silicate/ß-tricalcium phosphate (ZS/ß-TCP) composite ceramic scaffolds with different amounts of ZS (5, 10, and 15 wt%) were constructed using a three-dimensional fiber deposition (3DF) technique. The physicochemical, osteogenic and angiogenic properties of these interconnected macroporous scaffolds were investigated systematically. Simultaneously, GeneChip, alkaline phosphatase (ALP), western blot (WB) and polymerase chain reaction (PCR) were utilized to elucidate the underlying mechanism of the enhancement in osteogenic differentiation. The results showed that the incorporation of ZS significantly improved the mechanical performance by more than 5 fold in comparison with the ß-TCP ceramic scaffold (4.79 ± 0.99 MPa). The ZS modified ß-TCP scaffolds greatly supported the cytoactivity, adhesion, proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs). The expression levels of osteogenic genes and proteins as well as angiogenic genes were markedly upregulated by the sustained release of bioactive ions (mainly Si and Zn) from the composite scaffolds. The 10ZS/ß-TCP demonstrated the best overall performance in vitro. Moreover, the 10ZS/ß-TCP displayed a high bone volume fraction, bone maturity and angiogenesis after implantation in the rat skull defects for 6 weeks. It was further verified that ZS/ß-TCP scaffolds stimulated the osteogenic differentiation of mBMSCs by activating the p38 signaling pathway directly. The 10ZS/ß-TCP ceramic scaffold holds great potential for the fast repair of bone defects, and deep understanding of the mechanism will facilitate the formulation of new strategies for bone repair.

Zinc-doped calcium silicate additive accelerates early angiogenesis and bone regeneration of calcium phosphate cement by double bioactive ions stimulation and immunoregulation.

Calcium phosphate cement (CPC), a popular injectable bone defect repairing material, has deficiencies in stimulating osteogenesis and angiogenesis. To overcome the weaknesses of CPC, zinc-doped calcium silicate (Zn-CS) which can release bioactive silicon (Si) and zinc (Zn) ions was introduced to CPC. The physicochemical and biological properties of CPC and its composites were evaluated. Firstly, the most effective addition content of calcium silicate (CaSiO3, CS) in promoting the in vitro osteogenesis was first sorted out. On this basis, the most effective Zn doping content in CS for improving osteogenic differentiation of CPC-based composites was screened out. Finally, the immunoregulation of CS/CPC and Zn-CS/CPC in promoting angiogenesis and osteogenesis was studied. The results showed that the most effective incorporation content of CS was 10 wt%. Zn at a doping content of 30 mol% in CS (30Zn-CS) further enhanced the osteogenic capacity of CS/CPC and simultaneously maintained excellent proangiogenic activity. CS/CPC and 30Zn-CS/CPC promoted the recruitment of macrophages and enhanced M2 polarization while inhibiting M1 polarization, which was beneficial to the early vascularization as well as subsequent new bone formation. When implanted into the femoral condylar defects of rabbits, 30Zn-CS/CPC showed high in vivo materials degradation rate, angiogenesis and osteogenesis, due to the synergistic effects of Si and Zn on bio-stimulation and immunoregulation. This study shed light on the synergistic effects of Si and Zn on regulating the angiogenic, osteogenic, and immunoregulatory activity, and 30Zn-CS/CPC is expected to repair the lacunar bone defects effectively.

Fabrication of strontium carbonate-based composite bioceramics as potential bone regenerative biomaterials.

Strontium carbonate (SrC) bioceramics are proposed as potential biomaterials to efficaciously repair the bone defects. However, the development of SrC bioceramics is restricted by their intrinsic low mechanical strength. In this study, SrC-based composite bioceramics (SrC-SrP) were fabricated by incorporating strontium-containing phosphate glass (SrP). The results indicated that aside from the main crystalline phase SrC, new compounds were generated in the SrC-SrP bioceramics. Incorporating 10 wt% SrP promoted densification, thus dramatically improving compressive strength of SrC-SrP bioceramics. The SrC-SrP bioceramics facilitated apatite precipitation on their surface, and sustainedly released strontium, phosphorus and sodium ions. Compared with the well-known ß-tricalcium phosphate bioceramics, the SrC-SrP bioceramics with certain amounts of SrP enhanced proliferation, alkaline phosphatase activity and osteogenesis-related gene expressions of mouse bone mesenchymal stem cells. The SrC-SrP bioceramics with appropriate constituent can serve as novel bone regenerative biomaterials.

Preparation and characterization of novel lithium magnesium phosphate bioceramic scaffolds facilitating bone generation.

Both magnesium and lithium are able to stimulate osteogenic and angiogenic activities. In this study, lithium magnesium phosphate (Li0.5Mg2.75(PO4)2, Li1Mg2.5(PO4)2 and Li2Mg2(PO4)2) biomaterials were synthesized by a solid-state reaction method, and their bioceramic blocks and scaffolds were fabricated by compression molding and 3D printing, respectively. The results indicated that the lithium magnesium phosphates consisted of the Mg3(PO4)2 phase and/or LiMgPO4 phase. Compared with the lithium-free Mg3(PO4)2 bioceramics, the lithium magnesium phosphate bioceramics showed a lower porosity and consequently a higher compressive strength, and stimulated in vitro cellular proliferation, osteogenic differentiation and proangiogenic activity. In vivo results manifested that the Li2Mg2(PO4)2 bioceramic scaffolds efficiently promoted bone regeneration of critical-size calvarial defects in rats. Benefiting from the high compressive strength and capacity of stimulating osteogenesis and angiogenesis, the Li2Mg2(PO4)2 bioceramic scaffolds are considered promising for efficiently repairing the bone defects.

Enhancing the bioactivity of hydroxyapatite bioceramic via encapsulating with silica-based bioactive glass sol.

Although hydroxyapatite (HA) bioceramic has excellent biocompatibility and osteoconductivity, its high chemical stability results in slow degradation which affects osteogenesis, angiogenesis and clinical applications. Silica-based bioglass (BG) with superior biological performance has been introduced into HA bioceramic to overcome this insufficiency; however, the composite bioceramics are usually prepared by traditional mechanical mixture of HA and BG powders, which tremendously weakens their mechanical performance. In this research, BG-modified HA bioceramics were prepared by the use of BG sol encapsulated HA powders. The results showed that introducing 1 and 3 wt% BG allowed the HA-based bioceramics to maintain the high compressive strength (>300 MPa), improved the apatite mineralization activity, and played an important role in cellular response. The bioceramic modified with 1 wt% BG (1BG/HA) remarkably enhanced in vitro cell proliferation, osteogenic and angiogenic activities. This present work provides a new strategy to improve the biological performance of bioceramics and the HA-based bioceramics with 1 wt% BG can be as a promising candidate material for bone repair.

Conjunction of gallium doping and calcium silicate mediates osteoblastic and osteoclastic performances of tricalcium phosphate bioceramics.

Gallium-containing biomaterials are considered promising for reconstructing osteoporotic bone defects, owing to the potent effect of gallium on restraining osteoclast activities. Nevertheless, the gallium-containing biomaterials were demonstrated to disturb the osteoblast activities. In this study, tricalcium phosphate (TCP) bioceramics were modified by gallium doping in conjunction with incorporation of calcium silicate (CS). The results indicated that the incorporation of CS promoted transition ofß-TCP toα-TCP, and accelerated densification process, but did not improve the mechanical strength of bioceramics. The silicon released from the composite bioceramics diminished the inhibition effect of released gallium on osteoblast activities, and maintained its effect on restraining osteoclast activities. The TCP-based bioceramics doped with 2.5 mol% gallium and incorporated with 10 mol% CS are considered suitable for treating the bone defects in the osteoporotic environment.

Bioactive strontium ions/ginsenoside Rg1-incorporated biodegradable silk fibroin-gelatin scaffold promoted challenging osteoporotic bone regeneration.

Autogenous healing of osteoporotic fractures is challenging, as the regenerative capacity of bone tissues is impaired by estrogen reduction and existed pro-inflammatory cytokines. In this study, a biofunctional ginsenoside Rg1 and strontium-containing mineral (SrHPO4, SrP)-incorporated biodegradable silk fibroin-gelatin (SG) scaffold (Rg1/SrP/SG) was developed to stimulate the osteoporotic bone repair. The incorporation of 15 wt% SrP significantly enhanced the mechanical strength, stimulated the osteogenic differentiation of mouse bone marrow mesenchymal stem cells, and suppressed the osteoclastogenesis of RAW264.7 in a concentration-related manner. The loading of Rg1 in SG and 15SrP/SG scaffolds obviously promoted the angiogenesis of human umbilical vein endothelial cells via activating the expression of vascular endothelial growth factor and basic fibroblast growth factor genes and proteins. The bioactive strontium ions (Sr2+) and Rg1 released from the scaffolds together mediated lipopolysaccharide-treated macrophages polarizing into M2 type. They downregulated the expression of inflammatory-related genes (interleukin (IL)-1ß, tumor necrosis factor α, and IL-6) and stimulated the expression of genes related to anti-inflammation (Arginase and IL-10) as well as bone repair (BMP-2 and PDGF-BB) in the macrophages. The in vivo results also displayed that SrP and Rg1 significantly promoted the bone repair effect of SG scaffolds in osteoporotic critical-sized calvarial defects. Besides, the degradation rate of the scaffolds was close to the bone regeneration rate. Therefore, the simultaneous addition of SrP and Rg1 is a promising way for facilitating the osteoporotic bone repair activity of SG scaffolds via promoting the osteogenesis and angiogenesis, as well as inhibiting the osteoclastogenesis and inflammation.

Physicochemical Properties, In Vitro Degradation, and Biocompatibility of Calcium Phosphate Cement Incorporating Poly(lactic-co-glycolic acid) Particles with Different Morphologies: A Comparative Study.

Calcium phosphate cement (CPC) is one of the most promising synthetic biomaterials for bone defect repair, but its low degradation rate and the lack of macropores restrict its repair effect. Poly(lactic-co-glycolic acid) (PLGA) is commonly used as an in situ pore forming agent in CPC, and the morphology of PLGA would affect the properties of CPC. In this study, three kinds of PLGA particles with different morphologies, including dense PLGA microspheres, dense milled PLGA particles with an irregular shape, and porous PLGA microspheres, were respectively incorporated into CPC matrix. The influences of the morphology of PLGA particles on the setting time, porosity, mechanical properties, in vitro degradation, and cytocompatibility of CPC were comparatively investigated. The results showed that the CPC composites containing dense spherical and irregularly shaped PLGA particles showed proper setting time and better compressive strength, but the CPC composite incorporating porous PLGA microspheres significantly prolonged the final setting time and dramatically decreased the compressive strength of CPC. The CPC composite containing irregularly shaped PLGA particles has shown a slightly faster in vitro degradation rate than that containing dense PLGA microspheres. In addition, the CPC composites containing dense PLGA particles were beneficial for cell proliferation. Taken together, the dense PLGA particles are suitable for use as in situ pore forming agents in the CPC matrix, and meanwhile, the dense irregularly shaped PLGA particles are more easily prepared with low cost.

Novel Extrusion-Microdrilling Approach to Fabricate Calcium Phosphate-Based Bioceramic Scaffolds Enabling Fast Bone Regeneration.

This study proposes a novel approach, termed extrusion-microdrilling, to fabricate three-dimensional (3D) interconnected bioceramic scaffolds with channel-like macropores for bone regeneration. The extrusion-microdrilling method is characterized by ease of use, high efficiency, structural flexibility, and precision. The 3D interconnected ß-tricalcium phosphate bioceramic (EM-TCP) scaffolds prepared by this method showed channel-like square macropores (∼650 µm) by extrusion and channel-like round macropores (∼570 µm) by microdrilling as well as copious micropores. By incorporating a strontium-containing phosphate-based glass (SrPG), the obtained calcium phosphate-based bioceramic (EM-TCP/SrPG) scaffolds had noticeably higher compressive strength, lower porosity, and smaller macropore size, tremendously enhanced in vitro proliferation and osteogenic differentiation of mouse bone marrow stromal cells, and suppressed in vitro osteoclastic activities of RAW264.7 cells, as compared with the EM-TCP scaffolds. In vivo assessment results indicated that at postoperative week 6, new vessels and a large percentage of new bone tissues (24-25%) were formed throughout the interconnected macropores of EM-TCP and EM-TCP/SrPG, which were implanted in the femoral defects of rabbits; the bone formation of the EM-TCP group was comparable to that of the EM-TCP/SrPG group. At 12 weeks postimplantation, the bone formation percentage of EM-TCP was slightly reduced, while that of EM-TCP/SrPG with a slower degradation rate was pronouncedly increased. This work provides a new strategy to fabricate interconnected bioceramic scaffolds allowing for fast bone regeneration, and the EM-TCP/SrPG scaffolds are promising for efficiently repairing bone defects.

Effects of strontium amount on the mechanical strength and cell-biological performance of magnesium-strontium phosphate bioceramics for bone regeneration.

Magnesium and strontium are able to enhance osteogenesis and suppress osteoclastic activities simultaneously, and they were nontoxic in wide concentration ranges; these make the magnesium-strontium phosphate bioceramics suitable for treating osteoporotic bone defects. The aim of this study was to investigate the effects of strontium amount on the mechanical strength and cell-biological performance of magnesium-strontium phosphate [MgxSr3-x(PO4)2; 3-x = 0, 0.1, 0.25, 0.5, 0.75, 1] bioceramics, which were sintered at 1100 °C. The results indicated that the magnesium-strontium phosphate bioceramics except Mg2.9Sr0.1(PO4)2 and Mg2.25Sr0.75(PO4)2 bioceramics had considerable compressive strength. The variation in magnesium and strontium contents did not regularly affect the in vitro osteogenic differentiation and osteoclastic activities. The Mg2.75Sr0.25(PO4)2 bioceramic had the most desirable overall performance, as reflected by considerably high compressive strength, enhanced in vitro osteogenesis and inhibited osteoclastic activities. Therefore, the Mg2.75Sr0.25(PO4)2 bioceramic is considered a promising biomaterial for osteoporotic bone regeneration.

Enhanced osteogenesis of honeycomb ß-tricalcium phosphate scaffold by construction of interconnected pore structure: An in vivo study.

Pore structure plays an important role in the in vivo osteogenesis for bone repair materials. In this study, honeycomb ß-tricalcium phosphate (ß-TCP) scaffolds were prepared by extrusion method, and gelatin microspheres were used as porogens to modify the pore structure of the scaffolds. The honeycomb ß-TCP scaffolds were characterized by channel-like square macropores and unidirectional interconnection. To improve the pore interconnectivity of the scaffold, the spherical pores were formed in the channel walls by burning off the gelatin microspheres. Compared with unidirectional honeycomb ß-TCP scaffold, the honeycomb ß-TCP scaffold with interconnected pore structure had significantly higher porosity and faster degradation rate, at the expense of the mechanical strength. The in vivo assessment results demonstrated excellent osteogenesis of the honeycomb scaffolds. Moreover, the honeycomb ß-TCP scaffold with interconnected pore structure markedly promoted new bone formation in comparison with the unidirectional honeycomb ß-TCP scaffold. This work provides a new approach to prepare scaffolds with interconnected pore structure, and the honeycomb ß-TCP scaffold with interconnected pore structure is expected to serve as an efficient bone repair material.

Concentration-dependent osteogenic and angiogenic biological performances of calcium phosphate cement modified with copper ions.

Development of multifunctional bone grafting biomaterials with both osteogenesis and angiogenesis properties have earned increasing interest in the field of regenerative medicine. In the present investigation, copper-doped ß-tricalcium phosphate (Cu-TCP) powders were successfully synthesized. And Cu-containing calcium phosphate cement (Cu-CPC) was acquired through uniformly mixing CPC and Cu-TCP powders, with Cu-TCP serving as the donor of Cu2+. Cu-CPC exhibited suitable setting time, and the incorporation of Cu-TCP aggregating into CPC exhibited positive effect on the compressive strength while Cu2+ was in lower concentration. Investigation results showed that Cu-CPC had relatively low releasing amount of Cu2+, which was attributed to the re-bonding of Cu2+ into the newly formed HA crystals on surface. In vitro osteogenesis and angiogenesis properties of Cu-CPC were systematically evaluated through co-culture with mouse bone marrow stromal cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs) respectively. The results indicated dose-dependent biological functions of Cu2+ in Cu-CPCs. The mBMSCs and HUVECs showed well activity and attachment morphology on TCP/CPC, 0.05 Cu-TCP/CPC, 0.1 Cu-TCP/CPC. The upregulated osteogenic-related genes expression and angiogenic-related genes expression were detected with lower Cu2+ content. Taken together, Cu-containing CPC is of great potential for the regeneration of vascularized new bone.

Novel Strategy to Accelerate Bone Regeneration of Calcium Phosphate Cement by Incorporating 3D Plotted Poly(lactic-co-glycolic acid) Network and Bioactive Wollastonite.

Inefficient bone regeneration of self-hardening calcium phosphate cement (CPC) increases the demand for interconnected macropores and osteogenesis-stimulated substances. It remains a challenge to fabricate porous CPC with interconnected macropores while maintaining its advantages, such as plasticity. Herein, pastes containing CPC and wollastonite (WS) are infiltrated into a 3D plotted poly(lactic-co-glycolic acid) (PLGA) network to fabricate plastic CPC-based composite cement (PLGA/WS/CPC). The PLGA/WS/CPC recovers the plasticity of CPC after being heated above the glass transition temperature of PLGA. The presence of the 3D PLGA network significantly increases the flexibility of CPC in prophase and generates 3D interconnected macropores in situ upon its degradation. The addition of WS is helpful to improve the attachment, proliferation, and osteogenic differentiation of mouse bone marrow stromal cells in vitro. The in vivo experimental results indicate that PLGA/WS/CPC promotes rapid angiogenesis and bone formation. Therefore, the plastic CPC-based composite cement with a 3D PLGA network and wollastonite shows an obviously improved efficiency for repairing bone defects and is expected to facilitate the wider application of CPC in the clinic.

Improving osteogenesis of calcium phosphate bone cement by incorporating with lysine: An in vitro study.

Calcium phosphate bone cement (CPC) has attracted extensive interests from surgeons and material scientists. However, its actual application is still limited because of its poor osteogenesis. In this work, lysine, one of the essential components of proteins, was incorporated into the CPC to improve its osteogenesis ability. Effects of lysine on the phase, morphology, physicochemical properties, protein adsorption, lysine release and cytocompatibility of CPC were investigated. Results showed that lysine had no significant influence on the phase and morphology of the hydrated cements, but evidently raised the compressive strength, apparent porosity and setting time of the cements in a content-dependent manner of lysine. In contrast to the control, the lysine-incorporated CPCs had notably enhanced in vitro osteogenesis capability. It was supposed to be synergistically attributed to the improvements of fibronectin (FN) anchoring and bone mesenchymal stem cells (BMSCs) adhesion on the hydrated cements as well as the sustained release of bioactive amino acid molecules. Hence, lysine was expected to be applied as a novel bioactive admixture in the development of CPC with the improved osteogenesis ability and physicochemical properties for numerous orthopedic applications.

Strontium ranelate simultaneously improves the radiopacity and osteogenesis of calcium phosphate cement.

In a minimally invasive surgery of osteoporotic fractures, high radiopacity is necessary to monitor the delivery and positioning of injectable cements and good osteogenesis is indispensable. In this work, strontium ranelate (SrR), an agent for treating osteoporosis, is firstly used as a radiopaque agent for calcium phosphate cement (CPC). The addition of SrR does not affect the hydration products of CPC, but prolonged the setting time and decreased the compressive strength. The injectability of the cement was higher than 85% when SrR content is more than 10 wt%. The radiopacity of CPC is significantly improved by SrR and higher than cortical bone when the content of SrR is more than 5 wt%. The concentration of Sr ions released from CPC is increased by the increasing content of SrR, which is among 17-1329 µM. Moreover, CPCs with SrR significantly promote the osteogenic differentiation of mouse bone marrow mesenchymal stem cells and inhibit the osteoclastogenic differentiation of RAW264.7 cells. Based on its good radiopacity and osteogenesis, suppressed osteoclastogenesis and appropriate physicochemical properties, the radiopaque CPC with more than 10 wt% SrR is prospective to be a promising biomaterial for osteoporotic fracture repairing in minimal invasive surgery.