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In this article, the monomers epoxy succinic acid (ESA) and maleic acid ethanolamine (PTA) were prepared, and then the terpolymer scale inhibitor P(ESA-AA-PTA) was synthesized by aqueous solution polymerization using ESA, PTA, and acrylic acid (AA) as monomers. The structures of the synthesized monomers and polymers were characterized by FTIR. The optimum synthesis conditions of the terpolymer were obtained by static scale inhibition experiment, and the effects of the amount of scale inhibitor, test temperature, test time, and solution pH on the inhibition performance of the four scales, CaCO3, CaSO4, BaSO4, and SrSO4, were discussed. The results showed that the best CaCO3 scale inhibition efficiency was 85% when the molar ratio of ESA:AA:PTA was 1:1:0.5, the initiator dosage was 10 wt%, the polymerization time was 3.5 hours and the polymerization temperature was 95 °C. In the optimum water environment, the scale inhibition efficiency of CaCO3 scale and CaSO4 scale reached 100%, BaSO4 scale could reach 75% and SrSO4 scale could reach 54%. P(ESA-AA-PTA) had better scale inhibition properties than the majority of commercially available oilfield scale inhibitors. SEM and XRD results showed that the addition of P(ESA-AA-PTA) scale inhibitor hindered the growth of crystals and made the microscopic morphology of scale samples changed. [ABSTRACT FROM AUTHOR]

Abstract The problem of nosocomial infection is seriously escalating. Bacterial vaccines are indispensable for preventing infections caused by multi-drug resistant organisms. Some researchers have put forward the use of hydrogen peroxide (H 2 O 2) as a new technology platform for virus deactivation. This deactivated virus can induce the number of CD8+ T lymphocytes, which can enhance antiviral responses. Although, H 2 O 2 treatment has been rarely reported on the exploration of bacterial deactivation, H 2 O 2 deactivation of whole-cell bacteria could be a potential novel approach for bacterial vaccine development. Here we present a strategy for H 2 O 2 -deactivated bacterial whole-cell vaccines, for two major pathgens, Pseudomonas aeruginosa and Staphylococcus aureus. The proactive effects of vaccination were assessed in vitro and in vivo. H 2 O 2 -deactivation of bacterial vaccines retains more complete epitopes and exhibits lower toxicity, as compared to formaldehyde, a conventional deactivator that was investigated in this study. Furthermore, H 2 O 2 -deactivated bacterial vaccines induce anti-infection responses through enhancement of humoral immunity and cellular immunity. Vaccination with H 2 O 2 -deactivated whole-cell bacteria in mice mainly elicits whole-cell specific antibody titers and balances the IgG2a and IgG1 response, predominantly with IgG3 induction at the later stages, meanwhile provides opsonic protection against challenge with pathogens. Finally, H 2 O 2 deactivation of bacteria has been found to cause the release of bacterial DNA which is followed by NF-κB activation. These findings demonstrate that the deactivation of whole-cell bacteria with H 2 O 2 is potentially advantageous for immune responses. Considering the prevention of drug-resistant infections, this deactivation method could be simultaneously applied as an innovative strategy for bacterial vaccine development. Highlights • H 2 O 2 is an improved inactivator to maintain immunogenicity of bacterial vaccine, in comparison to formaldehyde. • The inactivation process using hydrogen peroxide is simple and convenient. • H 2 O 2 inactivated bacterial vaccines were able to balance the humoral and cellular immune responses in mice. [ABSTRACT FROM AUTHOR]

Periodontitis is a chronic inflammatory disease raising the risks of tooth-supporting structures destruction and even tooth loss. The way to reconstruct periodontal bone tissues in inflammatory microenvironment has been long in demand for periodontitis treatment. In this study, the lycium barbarum glycopeptide (LbGP) loaded gelatin-based scaffolds were fabricated for periodontitis treatment. Gelatin microspheres with suitable size were prepared by emulsification and gathered by oxidized sodium alginate to prepare heterogeneous bilayer gelatin-based scaffolds, and then they were loaded with LbGP. The prepared scaffolds possessed interconnected porous microstructures, good degradation properties, sufficient mechanical properties, sustained release behavior and well biocompatibility. In vitro experiments suggested that the LbGP loaded gelatin-based scaffolds could inhibit the expression of inflammatory factors (IL-1β, IL-6, and TNF-α), promote the expression of anti-inflammatory factor (IL-10), and the expression of osteogenic markers (BMP2, Runx2, ALP, and OCN) in PDLSCs under the LPS-stimulated inflammatory microenvironment. Moreover, in rat periodontitis models, the LbGP gelatin-based scaffolds would reduce the alveolar bone resorption of rats, increase the collagen fiber content of periodontal membrane, alleviate local inflammation and improve the expression of osteogenesis-related factors. Therefore, the LbGP loaded gelatin-based scaffolds in this study will provide a potential therapeutic strategy for periodontitis treatment. [ABSTRACT FROM AUTHOR]

Background: A novel and highly efficient method for integration stripe patterns into pore walls of 3‐D porous hydroxyapatite scaffolds (HAW) was developed using sugar spheres as porogens. In our previous research, the HAW were appropriate for the adhesion of cells and the formation of capillaries, coupled with excellent osteoconductive and osteoinductive potential. Numerous blood vessels and ectopic bone formation were observed when implanting HAW into the dorsal muscle of dogs. Aim/Hypothesis: To evaluate the osseointegration of dental implant at different time point inserted in HAW, which prior to be inserted for repairing canine segmental mandibular bone defects three months ago. Material and Methods: Eight adults and healthy beagle dogs were selected and divided into two groups randomly, bilateral mandibular premolars were extracted and two cylindrical bone defects of 8 mm in diameter and 10 mm in height were created. The HAW was inserted in the one side bone defect as test group, while autologous bone was used to fill the other side as control group. Three months later, a diameter of 4.0 mm × 10 mm Dentium implants were embedded into the middle of repair area. Four weeks and twelve weeks after implantation, imaging, histological and biomechanical methods were taken to evaluate the osseointegration of dental implant at 4 and 12 weeks respectively. Results: A well implant‐osseous healing was identified in both test and control group by X‐ray and CBCT at 12 weeks after implantation, while the control group showed a higher neogenetic bone density around the implant. Micro‐CT indicated a significant higher density difference in control group compared to the test one at four weeks (_I_P_i_ < 0.05), while the discrepancy disappeared at 12 weeks (_I_P_i_ > 0.05), which suggested similar conjunction were formed between the implant and the autologous bone as well as the HAW. Histologically, at four weeks both groups showed new bone formation, and lots of mature bone trabecula around implant thread at twelve weeks, simultaneously having detected Harvard tubule. No significant mechanical‐strength difference was found in mandible between the experimental group and control group (_I_P_i_ > 0.05). Conclusions and Clinical Implications: The HAW in vivo alone could induce new bone formation, thus might be a favorable remediation to repair canine segmental bone defects. Moreover, they could achieve fine osseointegration between implants and HAW, especially when it comes to 12 weeks.

Objective Methods Results Conclusion This study investigates the DP7‐C/miR‐26a complex as a stable entity resulting from the combination of miR‐26a with the immunomodulatory peptide DP7‐C. Our focus is on utilizing DP7‐C loaded with miR‐26a to modulate the immune microenvironment in bone and facilitate osteogenesis.The DP7‐C/miR‐26a complex was characterized through transmission electron microscopy, agarose electrophoresis, and nanoparticle size potentiometer analysis. Transfection efficiency and cytotoxicity of DP7‐C were assessed using flow cytometry and the CCK‐8 assay. We validated the effects of DP7‐C/miR‐26a on bone marrow mesenchymal stem cells (BMSCs) and macrophages RAW 264.7 through gene expression and protein synthesis assays. A comprehensive evaluation of appositional bone formation involved micro‐CT imaging, histologic analysis, and immunohistochemical staining.DP7‐C/miR‐26a, a nanoscale, and low‐toxic cationic complex, demonstrated the ability to enter BMSCs and RAW 264.7 via distinct pathways. The treatment with DP7‐C/miR‐26a significantly increased the synthesis of multiple osteogenesis‐related factors in BMSCs, facilitating calcium nodule formation in vitro. Furthermore, DP7‐C/miR‐26a promoted M1 macrophage polarization toward M2 while suppressing the release of inflammatory factors. Coculture studies corroborated these findings, indicating significant repair of rat skull defects following treatment with DP7‐C/miR‐26a.The DP7‐C/miR‐26a system offers a safer, more efficient, and feasible technical means for treating bone defects. [ABSTRACT FROM AUTHOR]

Objective: A lack of relevant research on Lycium barbarum polysaccharide‐glycoprotein (LBP) application in oral diseases. Here, we focused on the effect of LBP on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and periodontitis bone loss. Methods: Human periodontal ligament stem cells (hPDLSCs) were isolated and identified by flow cytometry. Alkaline phosphatase (ALP) activity, Alizarin Red staining, and combined qPCR and Western blot analyses were performed to elucidate the effects of LBP on the osteogenic potential of hPDLSCs. In vivo experiments were performed with the treatment of LBP in rat periodontal model. MicroCT scanning and histological analysis were conducted to evaluate osteogenesis in situ. Results: Human periodontal ligament stem cells (hPDLSCs) were successfully isolated and identified with CD90, CD29, and CD45. LBP enhanced hPDLSCs proliferation and migration and promoted RUNX2, ALP, Collagen I, and Osteocalcin expression through activating the ERK1/2 signaling pathway in vitro. The inflammatory factors, including interleukin 6 (IL‐6) and interleukin 8 (IL‐8) were reduced after LBP treatment. Alveolar bone resorption was significantly decreased in the LBP‐treated groups in vivo, and osteoclast was markedly decreased by LBP application. Conclusion: LBP promoted hPDLSC osteogenesis by targeting the ERK1/2 signaling pathway and reverse bone loss by reducing inflammation. These findings provided latent hope for LBP application in periodontal therapy. [ABSTRACT FROM AUTHOR]

Objective: The purpose was to evaluate whether a novel porous hydroxyapatite (HA) scaffold with a 25–30-µm groove structure (pHAMG) may improve bone osteogenesis, angiogenesis, and bone integration of titanium dental implants in animal models. Methods: The pHAMG was prepared by chemical precipitation method and its elemental composition and crystal structure were evaluated. The ability of the scaffolds to induce ectopic osteogenesis and the ability of scaffolds combined with titanium dental implants to induce orthotopic peri-implant angiogenesis, osteogenesis, and osteointegration were tested after implantation into the femur muscle pocket in rats and the mandibular defects in beagle dogs, respectively. The elemental composition was evaluated by SEM–EDS; the expression of the relevant osteogenic/inflammation marker and the anti-/pro-inflammation markers was evaluated by immunostaining and immunofluorescence, respectively. Results: In animal experiments with ectopic and peri-implant osteogenesis, pHAMG resulted in significantly larger neovascularization by hematoxylin–eosin staining, as well as deposition of collagen fibers by Masson staining than HA. Meanwhile, microgrooves in pHAMG upregulate more bone morphogenetic protein (BMP) 2 and interleukin-4 (IL-4) and -10 (IL-10) and downregulate more IL-1β and tumor necrosis factor-α (TNF-α) than that in HA. The pHAMG showed greater expression of arginase (Arg)-1 and lower expression of inducible nitric oxide synthase (iNOS) than HA. Conclusion: The novel pHAMG can better repair bone defects in ectopic and orthotopic model. It also transfers macrophages to anti-inflammatory phenotypes, promoting angiogenic and osteogenesis in scaffolds, and bone integration in implants. Clinical relevance: The novel pHAMG induce greater osteogenesis and angiogenesis which could be utilized in the clinical treatment. [ABSTRACT FROM AUTHOR]

Successfully treating bone infections is a major orthopedic challenge. Clinically, oral, intravenous, or intramuscular injections of drugs are usually used for direct or complementary treatment. However, once the drug enters the system, it circulates throughout the body, leading to an insufficient local dose and limiting the therapeutic effect because of the lack of targeting in the drug system. In this study, β-cyclodextrin, modified with poly (ethylene glycol) [PEG] and aspartic acid hexapeptide (Asp6-β-CD), was used to specifically target the hydroxyapatite (HA) component of the bone. It was then loaded with norfloxacin (NFX) to treat bone infections. The antibacterial ability of NFX was enhanced by loading it into Asp6-β-CD, because the solubility of Asp6-β-CD@NFX increased significantly. Moreover, Asp6-β-CD could target bone tissue in nude mice and showed significantly enhanced accumulation (10 times) than the unmodified β-CD. In addition, in a rat model of osteomyelitis, Asp6-β-CD@NFX targeted HA well and exerted its antibacterial activity, which reduced inflammation and promoted bone tissue repair. This study indicates that the Asp6-β-CD based drug delivery system can efficiently target bone tissue to enable potential applications for treating bone-related diseases. [Display omitted] • Asp6-β-CD was prepared to target the hydroxyapatite (HA) component of the bone. • The antibacterial ability of norfloxacin (NFX) was improved by being loaded in Asp6-β-CD. • Asp6-β-CD@NFX can target bone tissue to treat bone infection and promote bone repair. [ABSTRACT FROM AUTHOR]

Background and objective: As an important mediator of intercellular interaction and formation of extracellular bone matrix, porous scaffolds are widely used for bone regeneration. Accumulating evidences demonstrate that microRNA are involved in the regulation of scaffolds-induced bone regeneration. Recently, we revealed that miR-210-3p was highly expressed during osteogenesis induced by HAG. In present study, we further explored the molecular mechanism underlying the effect of miR-210-3p on osteogenic differentiation. Materials and methods: In this study, miR-210-3p mimics and inhibitors were synthesized and transfected into MC3T3-E1 cells to explore their effects on osteogenic differentiation. The expression of osteogenic marker (Alp and Runx2) were detected by real-time quantitative PCR (qRT-PCR) and western blotting. After osteogenesis induction for 7 days, Alp staining were used to detected osteoblast differentiation of MC3T3-E1 cells. CCK8 and Transwell assays were performed to detected cell proliferation and migration. Then, top ranking list of target genes of miR-210-3p obtained from TargetScan and the expression of BDNF were detected by qRT-PCR and ELISA. The relationship between miR-210-3p and BDNF was verified by luciferase report assay. Furthermore, the effect of BDNF on osteoblast differentiation was verified by transfecting siRNA or adding BDNF to the culture medium. Results: MiR-210-3p mimics markedly suppress osteogenic differentiation, cell migration and cell proliferation of MC3T3-E; nevertheless, silencing of miR-210-3p dramatically enhanced MC3T3-E1 osteogenesis, cell migration and proliferation. Furthermore, luciferase reporter assay verified that brain derived neurotrophic factor (BDNF) is a directly target of miR-210-3p. Moreover, BDNF siRNA significantly decreased the expression levels of ALP and cell migration. The addition of BDNF partially rescued the inhibition of osteogenesis by miR-210-3p. Conclusion: miR-210-3p inhibited the osteogenic differentiation via targeting BDNF. Our Results provide a promising target for regulating osteogenic differentiation. [ABSTRACT FROM AUTHOR]

The interconnectivity of the scaffold determines oxygen and nutrients transmission, and metabolic waste discharge, which plays a crucial role in cell migration, blood vessel, and tissue regrowth. In the present study, three types of porous hydroxyapatite scaffolds (HAS) with the same pore sizes but different interconnecting window diameters were fabricated by sugar spheres-leaching and heat treatment technique and were used to investigate the effect of interconnecting window diameter on ectopic angiogenesis and osteogenesis. In vitro cell culture experiments showed that the interconnectivity did not influence the performance of cells, whil e in vivo animal experiments revealed that the interconnecting window diameter of HAS impacted not only angiogenesis but also osteogenesis. The mean diameter of blood vessels was increased with the increase of interconnecting window diameter after 4 weeks of implantation, and the sample of mHAS (with about 0.25 w/m ratio of interconnecting window diameter to macro-pore diameter) exhibited the best osteogenesis after 12 weeks of implantation. This study provides a new reference for designing the porous structure of HAS effectively to enhance the new bone formation of bone tissue engineering scaffolds via vascularization in clinic application. [ABSTRACT FROM AUTHOR]

Scaffold materials used for bone defect repair are often limited by osteogenic efficacy. Moreover, microRNAs (miRNAs) are involved in regulating the expression of osteogenic-related genes. In previous studies, we verified the enhancement of osteogenesis using a grooved porous hydroxyapatite scaffold (HAG). In the present study, we analyzed the contribution of HAG to the osteogenic differentiation of human placenta-derived mesenchymal stem cells (hPMSCs) from the perspective of miRNA differential expression. Furthermore, results showed that miRNAs were differentially expressed in the osteogenic differentiation of hPMSCs cocultured with HAG. In detail, 16 miRNAs were significantly upregulated and 29 miRNAs were downregulated with HAG. In addition, bioinformatics analyses showed that the differentially expressed miRNAs were enriched in a variety of biological processes, including signal transduction, cell metabolism, cell junctions, cell development and differentiation, and that they were associated with osteogenic differentiation through axon guidance, mitogen-activated protein kinase, and the transforming growth factor beta signaling pathway. Furthermore, multiple potential target genes of these miRNAs were closely related to osteogenic differentiation. Importantly, overexpression of miR-146a-5p (an upregulated miRNA) promoted the osteogenic differentiation of hPMSCs, and miR-145-5p overexpression (a downregulated miRNA) inhibited the osteogenic differentiation of hPMSCs. [ABSTRACT FROM AUTHOR]

Gelatin and starch are considered as promising sustainable materials for their abundant production and good biodegradability. Efforts have been made to explore their medical application. Herein, scaffolds based on gelatin and starch with a preferred microstructure and antibacterial antioxidant property were fabricated by the emulsion template method. The dialdehyde starch was firstly combined with silver nanoparticles and curcumin to carry out the efficient hybrid antibacterial agent. Then, the gelatin microsphere of appropriate size was prepared by emulsification and gathered by the above agent to obtain gelatin-based scaffolds. The prepared scaffolds showed porous microstructures with high porosity of over 74 % and the preferred pore sizes of ∼65 μm, which is conducive to skin regeneration. Moreover, the scaffolds possessed a good swelling ability of over 640 %, good degradability of over 18 days, excellent blood compatibility, and cell compatibility. The promising antibacterial and antioxidant properties came from the hybrid antibacterial agent were affirmed. As expected, the gelatin-based scaffolds fabricated by the emulsion template method with a preferred microstructure can facilitate more adhered fibroblasts. In summary, gelatin-based scaffolds functionalized by starch-based complex expanded the application of abundant sustainable materials in the biomedical field, especially as antibacterial antioxidant wound dressings. [Display omitted] • Dialdehyde starch was applied to synthesize AgNPs and encapsulate curcumin. • Scaffolds with preferred microstructure were prepared by emulsion template method. • Antibacterial antioxidant gelatin-based scaffolds were yielded with starch complex. • The prepared gelatin-based scaffolds facilitated more adhered fibroblasts. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial peptides are promising alternative antimicrobial agents to combat MDR. DP7, an antimicrobial peptide designed in silico, possesses broad-spectrum antimicrobial activities and immunomodulatory effects. However, the effects of DP7 against Pseudomonas aeruginosa and biofilm infection remain largely unexplored.Objectives: To assess (i) the antimicrobial activity of DP7 against MDR P. aeruginosa; and (ii) the antibiofilm activity against biofilm infection. Also, to preliminarily investigate the possible antimicrobial mode of action.Methods: The MICs of DP7 for 104 clinical P. aeruginosa strains (including 57 MDR strains) and the antibiofilm activity were determined. RNA-Seq, genome sequencing and cell morphology were conducted. Both acute and chronic biofilm infection mouse models were established. Two mutants, resulting from point mutations associated with LPS and biofilms, were constructed to investigate the potential mode of action.Results: DP7, at 8-32 mg/L, inhibited the growth of clinical P. aeruginosa strains and, at 64 mg/L, reduced biofilm formation by 43% to 68% in vitro. In acute lung infection, 0.5 mg/kg DP7 exhibited a 70% protection rate and reduced bacterial colonization by 50% in chronic infection. DP7 mainly suppressed gene expression involving LPS and outer membrane proteins and disrupted cell wall structure. Genome sequencing of the DP7-resistant strain DP7R revealed four SNPs controlling LPS and biofilm production. gshA44 and wbpJ139 mutants displayed LPS reduction and motility deficiency, conferring the reduction of LPS and biofilm biomass of strain DP7R and indicating that LPS was a potential target of DP7.Conclusions: These results demonstrate that DP7 may hold potential as an effective antimicrobial agent against MDR P. aeruginosa and related infections. [ABSTRACT FROM AUTHOR]

Researches have revealed the vital roles of the generated immune environment via the response of immune cells growing on biomaterial surfaces in the bone healing process. HAS and novel constructed microgrooved patterns of HAS (HAS-G) are widely used as biocompatible ceramic, especially as a mimic of the natural bone matrix. However, it is unclear whether osteoimmune response induced by HAS and HAS-G affects the osteogenic differentiation of bone marrow stromal cells (BMSCs). RAW264.7 cells were seeded on different surface of materials and cytokines released by macrophages were detected by enzyme-linked immunosorbent assay. The cell viability and mitochondrial function of macrophages seeded on different surface of materials were detected. Then, the effects of modified inflammatory microenvironment by macrophages on osteogenesis of BMSCs were measured by performing ALP staining, Alizarin Red S staining, and western blot. We confirmed that HAS-G is more favorable for RAW cell attaching and subsequently regulated the expression and release of cytokines/chemokines. Decrease in interleukin-6 (IL-6) release was further confirmed for contributing significantly to improve mitochondrial function in RAW cells. HAS-G-conditioned medium promoted osteogenic differentiation in BMSCs and was reversed by IL-6 addition. Decrease in IL-6 contributes to downregulation of miR-214 and subsequently upregulated p38/JNK pathway, which is potentially contributes to osteogenic promotion by HAS-G. This study is the first report to reveal the effects of HAS-G on osteogenesis via immune response, which could lead to a new insight into novel material for the advantage of biomaterials for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Abstract The repair of large maxillofacial bony defects using regular scaffolds is restricted by the osteogenic effect. It was postulated that a novel porous hydroxyapatite (HA) scaffolds with a 25–30 µm groove structure (HAG) may counter this limitation. In this study we evaluated the biocompatibility of HAG scaffolds both in vitro and in vivo in beagle dogs by investigating the enhancement of scaffolds bioactivity and osteogenesis. Compared with a regular HA scaffolds, the HAG scaffolds significantly promoted human placenta-derived mesenchymal stem cell (hPMSC) osteogenic differentiation and the maturation of osteoblasts. This is achieved by increasing protein adsorption, as well as promoting directed growth and expression of osteogenic genes in vitro. The compressive strength of HAG scaffolds was significantly greater than HA in both dorsal muscle and the mandibular distraction area after in vivo implantation, with hematoxylin and eosin staining demonstrating new bone formation and vasculogenesis. Immunochemical staining and micro-CT scanning demonstrated increased expression of osteogenic factors (BMP2, OCN and COL-1) and bone density in the HAG scaffolds compared with HA. Based on the above results, we conclude that HAG scaffolds that have a groove structure induce greater osteogenesis and possess improved ostoegenesis which could be utilized in the clinical treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydrophobically associative polymers. • Cross-linked fracturing fluid has excellent performance. • The residue content is low, and the damage to the reservoir is small. A cyclic quaternary ammonium salt type hydrophobic monomer VIM-16 was synthesized by 1-vinylimidazole and 1-bromohexadecane, and the hydrophobically associative polymer PAAV was prepared with AM and AMPS. It was cross-linked with 0.3% zirconium acetylacetonate to form a viscoelastic fracturing fluid. The rheological properties of it were found to have good thickening and shear resistance properties. Using 0.2% gel breaker, the gel was completely broken. No residue, it was a low damage fracturing fluid. Scanning electron microscopy was used to observe the microscopic morphology, and the morphology after cross-linking to form the jelly showed a uniform, regular and ordered network structure. [ABSTRACT FROM AUTHOR]

Surface topography is known to regulate cellular behaviour including adhesion, proliferation and differentiation on 2d surfaces. It is remaining a challenge to integrate controlled surface topographies into pore surfaces of three-dimensional (3d) porous scaffolds for bone tissue engineering so as to direct the cell behaviour and inducing tissue growth. A novel and highly efficient method for integration stripe patterns into pore walls of 3-D porous hydroxyapatite (HA) scaffolds was developed using sugar spheres as porogens. The sugar spheres were accumulated as templates for HA scaffolds which were pre-heat-treated and placed in a humidity condition. The quantity of moisture on the surface of templates controlled the gelation of HA slurry prepared by dissolving powder into dilute chitin solution, so that the stripe pattern was formed on the pore wall after the HA slurry was solidified and the sugar sphere template was leached. Finally, the interconnected HA scaffold with tripe patterns on pore walls was fabricated after the sintering process. The advantage of the present process is that the interconnectivity of HA scaffold was maintained meanwhile the surface stripe pattern on pore wall was harvested. The resulted HA scaffold with surface stripe pattern is proposed to benefit cell attachment and tissue ingrowth. [ABSTRACT FROM AUTHOR]

Previous preliminary studies have suggested that hydroxyapatite with a grooved structure (HAG) scaffold has good osteogenic potential. This type of scaffold may aid osteogenesis during the repair of large maxillofacial bony defects. The ectopic osteogenic effect and underlying mechanism were further studied using porous HAG scaffold-based delivery of human placenta-derived mesenchymal stem cells (hPMSCs). A total of 18 dogs were randomly allocated into a HAG scaffold group and a HAG scaffold-based hPMSC (HAG/hPMSC) group, and three scaffolds were implanted into the dorsal muscle of each dog. Samples were taken for subsequent analysis and tested 4, 8 and 12 weeks following heterotopic implantation. H&E staining was used to study the osteogenic effect in dog dorsal muscles, and RNA sequencing (RNA-seq) was used for exploring the underlying osteogenic mechanism. The osteogenic ability and effector of the HAG/hPMSC group were significantly greater than those of the HAG scaffold group at 4 weeks after implantation. After 12 weeks, a mature bone plate structure was seen in the HAG/hPMSC group. RNA-seq demonstrated that various osteogenesis-related pathways participated at different stages of metabolism, and that the expression of collagen-1 and runt-related transcription factor 2 increased with implantation time. The present study preliminarily focused on the ectopic osteogenic effect of the porous HAG scaffold-based delivery of hPMSCs in vivo, which may be helpful for the improved application of HAG scaffolds in the future. [ABSTRACT FROM AUTHOR]

Angiogenesis is of great importance to bone regeneration, but it remains a significant challenge to induce sufficient angiogenesis and osteogenesis within bone grafts for large bone defect healing. The aim of this study is to investigate the effects of hydroxyapatite (HA) scaffold via a novel graded pore distribution approach on vascularization and osteoinduction. Two types of graded porous scaffolds were fabricated by sugar templates-leaching techniques: (1) one with large pores of 1100–1250 μm in the center and small pores of 500–650 μm at the periphery (HALS); (2) the other with small pores of 500–650 μm in the center and large pores of 1100–1250 μm at the periphery (HASL). In vivo data showed different pore size distribution had a remarkable impact on blood vessel formation during bone formation, which led to distinct localization of new bone within the defects. After one month of implantation, the diameters of the blood vessels infiltrated on the periphery of HASL were substantially larger than those in the center though the host blood vessels were successful in infiltrating throughout the whole scaffold. In contrast, vascularization within HALS appeared to be poor with very few blood vessels formed in the center, indicating heterogeneous vascularization in the scaffolds. After 3 months of implantation, we found that HASL induced more homogeneous bone formation in the whole bone graft but new bone was only found at the periphery of HALS. This study suggests that the pores size distribution in graded scaffolds cannot only affected early stage vascularization, but also influence late stage bone formation and remodeling. The architecture of larger pores at the periphery of graded scaffold may be capable of enhancing angiogenesis and osteogenesis during large size bone defect healing. Unlabelled Image • The pores size distribution not only affected the size and number of the developed blood vessels but also impacted the distribution of new bone formed in scaffolds. • Osteogenesis and angiogenesis both started at the periphery and advanced toward the center. • The architecture of HASL causing the uniform formation of new bone tissue in the whole scaffold. [ABSTRACT FROM AUTHOR]