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BACKGROUND: Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose, infection and inflammation. It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors, and has great application prospect in bone tissue engineering. OBJECTIVE: To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine, especially its osteogenic potential under high glucose, infection and inflammation conditions, and its biological safety, so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS: PubMed, WanFang, and CNKI were searched for relevant literature using the keywords of “berberine, bone defects, bone repair, bone regeneration, osteoinductive, osteoporosis, osteoblast, osteoclast, bone tissue engineering, bone, high glucose, diabetes, inflam*, infect*” in English and Chinese, respectively. A total of 105 literatures were selected for review. RESULTS AND CONCLUSION: Berberine can be used to treat multiple diseases including bone diseases, and it has the ability to promote bone regeneration. This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies. Studies have shown that it can play a role in bone repair by promoting osteogenesis, inhibiting osteoclast formation and activity, and preventing osteoporosis. It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin, PI3K/AKT, EGFR/MEK/p38MAPK, cAMP/PKA/CREB, ERK and other signaling pathways. Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose, infection and inflammation, which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site. Berberine also has the advantages of low toxicity, low price, easy access (currently it can be synthesized), which is a relatively ideal bone induction potential drug. In recent years, the application of berberine in the treatment of bone defect tends to be localized, mainly through the combination with bone tissue engineering technology to improve bioavailability, and has shown good bone repair effect and excellent biological safety in animal experiments. In addition, preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes, local infection and inflammation. In the future, more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine, and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength, efficacy and biological safety. [ABSTRACT FROM AUTHOR]

Cementum plays a crucial role in linking periodontal and dental tissues and maintaining tooth root stability. Regenerating cementum is essential for functional periodontal tissue regeneration. It is a significant focus in tissue engineering. Periodontal disease, prevalent among the middle-aged and elderly, can severely impact overall health. Effective periodontal tissue regeneration is vital for enhancing the elderly's health and quality of life. Despite the progress, the lack of ideal scaffold materials and methods makes cementum regeneration a persistent challenge. This review discusses the current state of cementum tissue engineering materials and addresses existing challenges, providing a foundation for future scaffold material development.

BACKGROUND: Three-dimensional (3D) printing is an emerging technology in the field of dentistry. It utilizes a layer-by-layer manufacturing technique to create scaffolds suitable for periodontal tissue engineering applications. Tissue scaffolds produced through 3D printing can possess controlled characteristics, including internal structure, porosity, and interconnectivity, making it an ideal strategy for periodontal tissue engineering. OBJECTIVE: To review the applications of 3D printed scaffolds in periodontal regeneration. METHODS: English search terms were “3D printing, periodontal tissue engineering, additive manufacturing, regenerative medicine, bioengineering, scaffold, bioprinting, periodontitis”. Chinese search terms were “3D printing, additive manufacturing, periodontal tissue engineering, scaffolds, bio-inks, bioprinting, tissue engineering”. Relevant literature published from 2000 to 2023 in PubMed and CNKI databases was retrieved and included in the review. RESULTS AND CONCLUSION: Over the past few decades, 3D printing technology has made significant progress and breakthroughs in tissue engineering and biomedical fields. 3D printing technology can provide highly personalized treatment programs, improve the suitability and therapeutic effect of therapeutic stents, and has broad application prospects in periodontal tissue engineering. In periodontal tissue engineering, 3D printing applications can better mimic the complex structures of biological tissues and manufacture biocompatible scaffold materials with suitable mechanical and rheological properties. The layer-bylayer construction of tissue engineering scaffolds through 3D printing not only enables the creation of precise and intricate scaffold models for personalized treatment of periodontal disease but also facilitates the incorporation of complex microstructures and channels within the scaffolds to promote cell growth and tissue regeneration. [ABSTRACT FROM AUTHOR]

Graphene family nanomaterials (GFNs) are highly popular in the field of bone tissue engineering because of their excellent mechanical properties, biocompatibility, and ability to promote the osteogenic differentiation of stem cells. GFNs play a multifaceted role in promoting the bone regeneration microenvironment. First, GFNs activate the adhesion kinase/extracellularly regulated protein kinase (FAK/ERK) signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes. Second, GFNs adapt to the mechanical strength of bone tissue, which helps to maintain osseointegration; by adjusting the stiffness of the extracellular matrix, they transmit the mechanical signals of the matrix to the intracellular space with the help of focal adhesions (FAs), thus creating a favorable physiochemical microenvironment. Moreover, they regulate the immune microenvironment at the site of bone defects, thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines. GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities, thus accelerating the repair process of bone defects. Multiple types of GFNs regulate the bone regeneration microenvironment, including scaffold materials, hydrogels, biofilms, and implantable coatings. Although GFNs have attracted much attention in the field of bone tissue engineering, their application in bone tissue regeneration is still in the basic experimental stage. To promote the clinical application of GFNs, there is a need to provide more sufficient evidence of their biocompatibility, elucidate the mechanism by which they induce the osteogenic differentiation of stem cells, and develop more effective form of applications.

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BACKGROUND: With the proven ability of traditional Chinese medicine such as icariin and berberine to promote bone regeneration by regulating various mechanisms and targets, researchers have combined active ingredients of traditional Chinese medicine with bone tissue engineering and found that they have unique advantages in treating bone defects. OBJECTIVE: Starting from the active ingredients of traditional Chinese medicines that promote bone formation, to screen cases of their effective combination with different drug-carrying scaffold materials, and summarize the active ingredients of traditional Chinese medicines that have the potential to be applied to bone tissue engineering. METHODS: CNKI, WanFang, PubMed, and Web of Science were searched for relevant literature published from 2000 to 2023, using the keywords of “bone tissue engineering, bone tissue-engineered scaffold materials, bone defect, bone repair, bone regeneration, traditional Chinese medicine” in Chinese and English. According to the inclusion and exclusion criteria, 87 papers were finally included for review. RESULTS AND CONCLUSION: There are various kinds of active ingredients of traditional Chinese medicine to promote bone regeneration, mainly including flavonoids, non-flavonoid polyphenols, alkaloids, glycosides. These active ingredients have anti-inflammatory and analgesic effects, promote osteoblasts, inhibit osteoclasts and promote early angiogenesis. The combination of active ingredients of traditional Chinese medicine with bone tissue engineering is effective in anti-inflammation, accelerating collagen and bone formation, and promoting the expression of osteogenic genes, which provides a theoretical basis for the application of traditional Chinese medicine in bone tissue regeneration, and at the same time provides a new idea for the repair of bone defects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Graphene is the thinnest, strongest, and toughest type of two-dimensional new crystal material, demonstrating significant advantages in biomedical applications. Angiogenesis and vascularization of bone are key factors in tissue repair and regeneration, and are effective ways to address vascular and osteogenic issues. OBJECTIVE: To review the characteristics and mechanisms of graphene and its derivatives in promoting angiogenesis activity and vascularizing bone, in order to provide a reference for their clinical application in vascular tissue repair and regeneration. METHODS: Using a computer to search for relevant literature included in PubMed, ScienceDirect, CNKI, and Wanfang databases, the Chinese search terms were “grapheme”, “angiogenesis, vascularization”, “vascularized bone”, and “endothelial cells”, while the English search terms were “graphene” “angiogenesis OR vascularization” “vascularized bone” “endothelial cells”. After excluding literature unrelated to the topic of the article, according to the inclusion and exclusion criteria, 62 articles were ultimately included for result analysis. RESULTS AND CONCLUSION: (1) At present, graphene oxide has been studied more and is the most widely used in graphene and its derivatives. (2) Graphene and its derivatives are suitable for heart, bone, nerve, and wound healing related diseases. (3) Graphene and its derivatives have excellent physical and chemical properties and biological properties, but they have potential cytotoxicity. We should pay attention to its biological safety in application. (4) The application of graphene and its derivatives requires further research to demonstrate the optimal size and concentration and measures to reduce toxicity. (5) On the cellular level, graphene and its derivatives can promote angiogenic activity by tip endothelial cell phenotype, mesenchymal stem cell adhesion and proliferation, and vascular smooth muscle cell growth. (6) On the molecular level, graphene and its derivatives can increase the expression of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and activate reactive oxygen species/nitric oxide synthase/nitric oxide signaling pathway, lysophosphatilate R6/Hippo-YAP pathway, stromal cell-derived factor-1/vascular endothelial growth factor and ZEB 1/Notch1 pathway. (7) Grapheme oxide and graphene oxide-copper phosphorylated extracellular regulatory protein kinase and activated hypoxia-inducible factor-1, thereby promoting the up-regulation of vascular endothelial growth factor and bone morphogenetic protein-2 expression, and promoting angiogenesis and vascularized bone. (8) In summary, graphene and its derivatives, especially graphene oxide, have great application prospects in the repair and regeneration of vascularized tissues due to their excellent biological properties, good angiogenesis and vascularized bone ability. [ABSTRACT FROM AUTHOR]

Abstract Hepatic osteodystrophy (HOD) is a metabolically associated bone disease mainly manifested as osteoporosis with the characteristic of bone loss induced by chronic liver disease (CLD). Due to its high incidence in CLD patients and increased risk of fracture, the research on HOD has received considerable interest. The specific pathogenesis of HOD has not been fully revealed. While it is widely believed that disturbance of hormone level, abnormal secretion of cytokines and damage of intestinal barrier caused by CLD might jointly affect the bone metabolic balance of bone formation and bone absorption. At present, the treatment of HOD is mainly to alleviate the bone loss by drug treatment, but the efficacy and safety are not satisfactory. Mesenchymal stromal cells (MSCs) are cells with multidirectional differentiation potential, cell transplantation therapy based on MSCs is an emerging therapeutic approach. This review mainly summarized the pathogenesis and treatment of HOD, reviewed the research progress of MSCs therapy and the combination of MSCs and scaffolds in the application of osteoporotic bone defects, and discussed the potential and limitations of MSCs therapy, providing theoretical basis for subsequent studies.

Hepatic osteodystrophy (HOD) is a metabolically associated bone disease mainly manifested as osteoporosis with the characteristic of bone loss induced by chronic liver disease (CLD). Due to its high incidence in CLD patients and increased risk of fracture, the research on HOD has received considerable interest. The specific pathogenesis of HOD has not been fully revealed. While it is widely believed that disturbance of hormone level, abnormal secretion of cytokines and damage of intestinal barrier caused by CLD might jointly affect the bone metabolic balance of bone formation and bone absorption. At present, the treatment of HOD is mainly to alleviate the bone loss by drug treatment, but the efficacy and safety are not satisfactory. Mesenchymal stromal cells (MSCs) are cells with multidirectional differentiation potential, cell transplantation therapy based on MSCs is an emerging therapeutic approach. This review mainly summarized the pathogenesis and treatment of HOD, reviewed the research progress of MSCs therapy and the combination of MSCs and scaffolds in the application of osteoporotic bone defects, and discussed the potential and limitations of MSCs therapy, providing theoretical basis for subsequent studies. [ABSTRACT FROM AUTHOR]

To prove that calcium alginate beads can be used as scaffolds during in vitro culture.

In this study, sodium alginate (SA)/Antarctic krill protein(AKP)/Genipin (GP) scaffold was obtained by freeze-drying, in which Antarctic krill protein was used as enhanced the cell adsorption activity of the materials; GP and Ca2+, which have very low cytotoxicity, were selected to cross-link AKP and SA in steps, the interpenetrating network structure of "covalent cross-linking-ion complex-hydrogen bonding" was finally constructed. By changing the content of GP, the structure, surface morphology, mechanical properties, water absorption, water retention, and cytotoxicity of the scaffold were studied using FTIR, SEM, and other test methods. The results showed that the pore area of the prepared SA/AKP/GP scaffolds exhibited an increase and then a decrease with the increase of GP content; the fracture strength and elongation at break exhibited an increase and then a decrease with the increase of GP content. The breaking strength and elongation at break achieved their maximum values of 32.9 MPa and 4.43% when the content of GP hit 0.8%; The scaffold had good water absorption and water retention; The cytotoxicity grade of the scaffold was grade 0, and the addition of AKP made the fibroblasts have good growth and proliferation ability on the scaffold. [ABSTRACT FROM AUTHOR]

The receptor activator of NF-κB ligand (RANKL)-binding peptide is known to accelerate bone morphogenetic protein (BMP)-2-induced bone formation. Cholesterol-bearing pullulan (CHP)-OA nanogel-crosslinked PEG gel (CHP-OA nanogel-hydrogel) was shown to release the RANKL-binding peptide sustainably; however, an appropriate scaffold for peptide-accelerated bone formation is not determined yet. This study compares the osteoconductivity of CHP-OA hydrogel and another CHP nanogel, CHP-A nanogel-crosslinked PEG gel (CHP-A nanogel–hydrogel), in the bone formation induced by BMP-2 and the peptide. A calvarial defect model was performed in 5-week-old male mice, and scaffolds were placed in the defect. In vivo μCT was performed every week. Radiological and histological analyses after 4 weeks of scaffold placement revealed that the calcified bone area and the bone formation activity at the defect site in the CHP-OA hydrogel were significantly lower than those in the CHP-A hydrogel when the scaffolds were impregnated with both BMP-2 and the RANKL-binding peptide. The amount of induced bone was similar in both CHP-A and CHP-OA hydrogels when impregnated with BMP-2 alone. In conclusion, CHP-A hydrogel could be an appropriate scaffold compared to the CHP-OA hydrogel when the local bone formation was induced by the combination of RANKL-binding peptide and BMP-2, but not by BMP-2 alone. [ABSTRACT FROM AUTHOR]

Cartilage is a kind of translucent tissue whose main function is to transmit and absorb stress as well as reduce friction. Due to the complexity of structure and function, damaged cartilage is difficult to repair and regenerate. The treatment of cartilage defect is still a major clinical problem. With the vigorous development of regenerative medicine, tissue engineering artificial cartilage technology is expected to play an important role in the field of cartilage repair and treatment. In this review, the anatomical structure and functional characteristics of different layers of natural articular cartilage have been firstly introduced. Then, the latest progress of artificial cartilage tissue engineering technology has been summarized from the aspects of artificial cartilage scaffold construction materials, structural design and preparation technology. Finally, the main problems and future development directions of artificial cartilage scaffolds have been discussed. This review may provide reference for relevant research in the future. [ABSTRACT FROM AUTHOR]

Endometrial damage is an important factor leading to infertility and traditional conventional treatments have limited efficacy. As an emerging technology in recent years, stem cell therapy has provided new hope for the treatment of this disease. By comparing the advantages of stem cells from different sources, it is believed that menstrual blood endometrial stem cells have a good application prospect as a new source of stem cells. However, the clinical utility of stem cells is still limited by issues such as colonization rates, long-term efficacy, tumor formation, and storage and transportation. This paper summarizes the mechanism by which stem cells repair endometrial damage and clarifies the material basis of their effects from four aspects: replacement of damaged sites, paracrine effects, interaction with growth factors, and other new targets. According to the pathological characteristics and treatment requirements of intrauterine adhesion (IUA), the research work to solve the above problems from the aspects of functional bioscaffold preparation and multi-functional platform construction is also summarized. From the perspective of scaffold materials and component functions, this review will provide a reference for comprehensively optimizing the clinical application of stem cells.

Hydrogel, a functional polymer material, has emerged as a promising technology for therapies for periodontal diseases. It has the potential to mimic the extracellular matrix and provide suitable attachment sites and growth environments for periodontal cells, with high biocompatibility, water retention, and slow release. In this paper, we have summarized the main components of hydrogel in periodontal tissue regeneration and have discussed the primary construction strategies of hydrogels as a reference for future work. Hydrogels provide an ideal microenvironment for cells and play a significant role in periodontal tissue engineering. The development of intelligent and multifunctional hydrogels for periodontal tissue regeneration is essential for future research. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, the construction of engineered adipose tissue through seed cells, scaffold materials and extracellular microenvironment is one of the most potential directions for use in soft-tissue defect reconstructions. However, graft resorption attributed to lack of effective vascular network and blood supply is a major limitation for wider application of adipose tissue engineering. OBJECTIVE: To review the related research on how to establish a blood vessel network and effective engineered adipose tissue vascularization based on hydrogel scaffold. METHODS: The computer was used to search for articles on CNKI, Wanfang, and PubMed databases from January 2010 to June 2020. The search terms were “tissue engineering, adipose tissue, adipose-derived stem cell, hydrogel, vascularization” in Chinese and English. Relevant articles were summarized and finally 88 articles were included to analyze the results. RESULTS AND CONCLUSION: There are four main vascularization strategies for tissue engineered fat constructed with hydrogel materials: Tissue engineering chamber model; adipose-derived stem cells co-cultured with vascular endothelial cells; hydrogel scaffolds loaded with cytokines; application of suitable hydrogel scaffold with angiogenic properties. Therefore, the application of hydrogel materials to establish highly biomimetic adipose tissue units, combined with effective vascularization techniques, will further improve the efficiency of soft tissues repair and reconstruction. [ABSTRACT FROM AUTHOR]

Demineralized dentin matrix (DDM) is used as a tissue regeneration scaffold. Effective preservation of DDM benefits clinical applications. Cryopreservation and freeze-drying may be effective methods to retain DDM mechanical properties and biological activity. Human periodontal ligament stem cells (hPDLSCs) isolated using enzymatic dissociation were identified by multidirectional differentiation and flow cytometry. DDM was prepared with EDTA and divided into four groups: fresh DDM (fDDM), room temperature-preserved DDM (rtDDM), cryopreserved DDM (cDDM) and freeze-dried DDM (fdDDM). The DDM surface morphology was observed, and microhardness was detected. Transforming growth factor-β1 (TGF-β1), fibroblast growth factor (FGF) and collagen-Ⅰ (COL-Ⅰ) concentrations in DDM liquid extracts were detected by enzyme-linked immunosorbent assay (ELISA). The hPDLSCs were cultured with DDM liquid extracts. The effect of DDM on cells proliferation was examined by CCK-8 assay. The effect of DDM on hPDLSC secreted phosphoprotein-1 (SPP1), periostin (POSTN) and COL-Ⅰ gene expression was examined by real-time qPCR. cDDM dentinal tubules were larger than those of the other groups. The three storage conditions had no significant effect on DDM microhardness and COL-Ⅰ concentration. However, TGF-β1 and FGF concentrations decreased after storage, with the greatest change in rtDDM, followed by fdDDM and cDDM. The liquid extracts of fDDM, cDDM and fdDDM slightly inhibited hPDLSCs proliferation, but those of rtDDM had no significant effect. The hPDLSCs cultured with fDDM, cDDM and fdDDM liquid extracts showed increased SPP1, POSTN and COL-Ⅰ gene expression. Cryopreservation and freeze-drying better maintain the mechanical properties and biological activity of DDM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Self-healing hydrogels are scaffold materials with superior self-healing capability and biocompatibility, and are widely used in bone tissue engineering. OBJECTIVE: To introduce the gelatin mechanism and composition of self-healing hydrogels and summarize their applications in bone tissue engineering. METHODS: The first author searched both Chinese and English articles with key words "self-healing hydrogels; bone tissue engineering; bone regeneration" on CNKl, Wanfang, VIP, PubMed, Embase and Web of Science databases published from 2000 to 2020. Totally 69 eligible articles were selected for review. RESULTS AND CONCLUSION: The gelation mechanisms of self-healing hydrogels include dynamic covalent bonds, supramolecular bonds and multi-mechanism cross-links. Self-healing hydrogels can be composed of natural polymers, synthetic polymers and nanocomposites. Self-healing hydrogels have been found to be applied in bone tissue engineering through scaffold modification as stem cells delivery vehicle. The application of self-healing hydrogels in bone tissue engineering can be broaden by enhancing the mechanical properties of the hydrogel while maintaining its self-healing capability. Additionally, the specific mechanism for better superiority of self-repairing hydrogels over traditional hydrogels in bone tissue engineering is still unclear. [ABSTRACT FROM AUTHOR]

Currently, cell transplantation in combination with scaffold materials are one of the main strategies in periodontal bone tissue engineering. In periodontal bone tissues, the stiffness and spatial structure of tissues such as alveolar bone and cementum differ, and the difference in mechanical properties of scaffolds also has disparate effects on the proliferation and differentiation of stem cells. Accumulating evidence shows that mechanical stimulating factors such as matrix stiffness and scaffold topography modulate biological behaviors of various seeding cells, including adipose-derived stem cells and periodontal ligament stem cells. A hard matrix can promote cytoskeletal stretching of stem cells, leading to nuclear translocation of Yes-associated protein (YAP) and promoting osteogenic differentiation by upregulating alkaline phosphatase (ALP) and osteocalcin (OCN) via the Wnt/β-catenin pathway. The topologic structure of scaffolds can affect cell adhesion and cytoskeletal remodeling, increase the hardness of cells and promote the osteogenic differentiation of stem cells. In this paper, the effects of mechanical stimulation on the differentiation of stem cells in periodontal bone tissue engineering are reviewed.

Biomaterials have a vital role in the field of tissue engineering. In this study, we have developed a collagen hybrid scaffold comprising Annona reticulata fruit polysaccharide with a synergistic combination of Tetrahydrocurcumin (THC)-loaded ethyl cellulose (EC) microspheres with cinnamon bark extract as a cross-linking agent. Response Surface Methodology (RSM) was used to optimize the parameters for microwave-assisted extraction of polysaccharides from Annona reticulata. Further, the structural features of extracted polysaccharides were characterized by 13C CP/MAS NMR, LC-MS-MS, XRD, and TGA. The polysaccharide showed strong antioxidant activity analyzed by the DPPH method. The hybrid scaffold exhibits porous and interconnected morphology and shows better thermal stability due to strong interaction. The antimicrobial activity and sustained release of THC suggest that the hybrid scaffold could be an excellent biomaterial for antibacterial wound dressing applications.

BACKGROUND: Cell sheet technology has broad application prospects in tissue regeneration and repair. What is more, it also has an important role and application value in the field of bone tissue engineering. OBJECTIVE: To review the application and existing problems of cell sheet technology in bone tissue engineering. METHODS: CNKI, PubMed, and Elsevier were searched for relevant articles regarding the application of cell sheet technology in bone tissue engineering published from January 2000 to July 2021. The key words were “cell sheet technology, cell sheet, bone, bone defect, bone repair, tissue engineering, bone tissue engineering” in Chinese and English, respectively. The article types were review, basic and clinical studies.RESULTS AND CONCLUSION: Cell sheet technology is a new technology for obtaining seed cells, which not only acquires the desired seed cells, but also retains the abundant extracellular matrices and cell-cell connections. Therefore, it has broad application prospects in tissue regeneration and repair. The current technologies for cell sheet preparation mainly include: temperature response systems, mechanical systems, magnetic response systems, light response systems, and pH systems. Various technologies have their own advantages and disadvantages in the preparation of cell sheets. Among them, temperature response systems and magnetic response systems are currently widely used. There are many types of cell sheets, which can be divided into different types of cell sheets according to different cell sources. It can also be divided into single-layer cell sheet, double-layer cell sheet, and multi-layer cell sheet according to the number of sheet layers. In terms of bone tissue engineering, the cell sheet technology can be used alone or combined with various other scaffolds to enhance its mechanical strength in the repair of bone defects. In addition, adding growth factors or small molecular substances into cell sheets provides new ideas for the application of cell sheets. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polycaprolactone based scaffolds have potential in dental pulp regeneration since its good thermal stability, excellent biocompatibility and tunable degradation rate. However, its hydrophilicity and bioactivity are poor. OBJECTIVE: To prepare microspheres with polycaprolactone-polydopamine-nano-hydroxyapatite (PCL-PDA-nHA), and explore its physical properties and the effects on the proliferation and mineralization of dental pulp cells. METHODS: The PCL microspheres were prepared by double emulsification method. The hydrophilicity and crystallinity were improved by the surface modification of dopamine and the PCL-PDA particles were obtained. Nano-hydroxyapatite coating was formed in situ on the surface of PCL-PDA microspheres by simulating body fluids (reaction 7-day group and reaction 14-day group) to obtain PCL-PDA-nHA microspheres. The physical and chemical properties of each group of microspheres were detected by scanning electron microscopy, X-ray photoelectron spectroscopy and protein adsorption experiment. Hemolysis test, coagulation factor activation test and platelet agglutination test were used to test the hemocompatibility of each group of microspheres. Four groups of microspheres were co-cultured with human dental pulp cells. Cell proliferation was detected by CCK-8 assay. The mineralization induction ability of the microspheres was analyzed using alkaline phosphatase, alizarin red and sirius red staining. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the four groups of microspheres were uniform and porous structure, and there was no significant difference in the diameter of microspheres; the porosity was 87.4% with pore diameter ranging from 20 μm to 50 μm. X-ray photoelectron spectroscopy showed that polydopamine and hydroxyapatite particles were successfully decorated on the microsphere surface. Protein adsorption experiment showed that the functional microspheres could enhance the adsorption of serum albumin. (2) Hemolysis experiment showed that the hemolysis rate of microspheres was below 1%, without obvious hemolysis. The coagulation factor activation experiment showed that each group of modified polycaprolactone microspheres had little effect on blood coagulation. Scanning electron microscopy showed that there was no obvious platelet aggregation on the surface of each group of microspheres. (3) CCK-8 assay demonstrated that cell proliferation on the surface of each group of modified microspheres was faster than that of PCL microspheres. (4) Alkaline phosphatase, alizarin red and sirius red staining exhibited that the mineralization induction ability of each group of modified microspheres was stronger than that of PCL microspheres, and the mineralization induction ability of PCL-PDA-nHA-14 day microspheres and PCL-PDA-nHA-7 day microspheres was stronger than that of PCL-PDA microspheres. (5) The results suggested that PCL-PDA-nHA nanospheres had good hemocompatibility, and could promote the proliferation and mineralization of human dental pulp cells. [ABSTRACT FROM AUTHOR]

Endothelial regeneration is a research hotspot in the field of dental pulp. The regeneration of endodontic blood flow is the bottleneck of dental pulp regeneration, and the applied scaffold material is the key to revascularization. Stent materials were reviewed. The literature review Results show that, depending on the source of the stent material used for endodontic revascularization, there are mainly natural, synthetic and composite materials. The natural scaffold materials used for vascular regeneration include chitosan, hyaluronic acid, bacterial cellulose, and proanthocyanidin; artificial scaffold materials include hydrogel, cryogel, and electrospinning. The bionic composite scaffold system with a double-layer tubular structure is low immunogenicity and good biocompatibility. Studies on the scaffold materials of bionic extracellular matrix, such as injectable hydrogels/microspheres, have promoted the development of dental pulp regeneration, that is, uniformly distributed scaffold materials in the root canal promote the generation of pulp-like tissue; Whether dental pulp tissue can establish effective blood circulation through the apical foramen remains a great challenge.

BACKGROUND: Polyetherketoneketone has excellent biocompatibility and is widely used in biomedical fields such as spine, joint and oral and maxillofacial surgery. OBJECTIVE: To summarize the synthesis of polyetherketoneketone and its research progress in medical applications. METHODS: PubMed, Web of Science and CNKI databases were searched for the articles concerning about the synthesis and development of polyetherketoneketone and their applications in the field of biomedicine with the search terms of “polyetherketoneketone, synthesis, scaffold material, implant, tissue engineering, biocompatibility” in English and Chinese, respectively. After initial screening of all articles according to inclusion and exclusion criteria, articles with higher relevance were included for review. RESULTS AND CONCLUSION: In recent years, with the rise of the combination of medical and engineering, polyetherketoneketone and its composites have been gradually applied to the fields of orthopedics, oral and maxillofacial surgery. In orthopedics, polyetherketoneketone and its compounds modified with different physical and chemical properties can not only maintain the elastic modulus similar to human bones, increase the hardness, but also improve its biocompatibility, increase its antibacterial properties, and promote osseointegration. In oral and maxillofacial surgery, it can be used as a dental implant matrix, frame, and snap ring for removable partial dentures. Polyetherketoneketone can not only maintain good aesthetic advantages, but also has good fatigue resistance and retention, which is comparable to the oral cavity. The bonding system can ensure sufficient bonding ability, so polyetherketoneketone has great potential as a dental restoration material. In-depth research on the modification of polyetherketoneketone and its compound is still a hot topic. Through continuous improvement of the performance of the material, more in vivo and in vitro experiments have been carried out to confirm the superiority of polyetherketoneketone as an implant material for orthopedics and oral and maxillofacial surgery to make clinical transformation and it will have very good application prospects. [ABSTRACT FROM AUTHOR]

Different fabrication techniques of 3D Scaffolds for bone tissue regeneration. [Display omitted] Meeting the escalating demands in biomedical applications has spurred the creation of diverse scaffolds, where the selection of materials and manufacturing techniques stands as a linchpin in fostering bone tissue formation. These scaffolds provide a fundamental structural framework that supports cell growth and differentiation. It is vital for tissue repair, addressing various biological requisites such as biocompatibility, biodegradability, and mechanical properties becomes imperative. This comprehensive review discusses recent advancements in the techniques for manufacturing 3D scaffolds tailored specifically for bone tissue engineering applications. Stereolithography, fused deposition modelling, selective laser sintering, binder jetting, electron beam melting, and bioprinting (including laser-based, inkjet and extrusion 3D bioprinting) are meticulously explored. Focusing on their respective applications, limitations, as well as advantages and disadvantages within the context of bone tissue regeneration. Furthermore, the article underscores the pivotal role of material selection as a potential solution to address challenges associated with bone grafts. It emphasizes the need for a nuanced understanding of the significant considerations regardless of the tissue type when designing or evaluating the suitability of scaffolds for integration into the expansive realm of tissue engineering. [ABSTRACT FROM AUTHOR]

Hydrogel, a functional polymer material, has emerged as a promising technology for therapies for periodontal diseases. It has the potential to mimic the extracellular matrix and provide suitable attachment sites and growth environments for periodontal cells, with high biocompatibility, water retention, and slow release. In this paper, we have summarized the main components of hydrogel in periodontal tissue regeneration and have discussed the primary construction strategies of hydrogels as a reference for future work. Hydrogels provide an ideal microenvironment for cells and play a significant role in periodontal tissue engineering. The development of intelligent and multifunctional hydrogels for periodontal tissue regeneration is essential for future research.

As an emerging functional polymer material, hydrogel has great potential for development, and is widely used in bioengineering. Because of its good biocompatibility, it has also gradually received attention in the medical field. Some studies have shown that hydrogel sustained-release system can promote the proliferation and adhesion of human periodontal ligament fibroblasts and effectively promote their differentiation into osteoblasts and cementoblasts. This paper briefly reviews the application of hydrogel to periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been confirmed that some biomedical magnesium alloy products have antibacterial properties, but the specific antibacterial mechanism is still unclear. OBJECTIVE: To investigate the antibacterial properties of biomedical Jiao Da Bio-Magnesium scaffold in vitro and explore possible mechanism. METHODS: Jiao Da Bio-Magnesium porous scaffold material extract was prepared. As the most common bacteria causing orthopedic implants infection, Escherichia coli and Staphylococcus aureus were selected for testing. The bacteriostasis rate was quantitatively evaluated by contact culture of the extraction solution. The bacteriostasis performance of the material was qualitatively evaluated by observing the bacterial morphology through scanning electron microscope. The alkaline phosphatase, conductivity, potassium ion, nucleic acid and protein content in bacterial extracellular liquid environment were detected. The possible antibacterial mechanism of Jiao Da Bio-Magnesium porous scaffold material extract was preliminarily explored. RESULTS AND CONCLUSION: (1) The bacteriostasis rate of Jiao Da Bio-Magnesium porous scaffold extract cultured with Escherichia coli for 12 hours ranged from 56.23% to 79.72%, while the Staphylococcus aureus group ranged from 62.34% to 76.07%. (2) Under scanning electron microscope, wizened form, smaller volume and scarcer distribution were observed. (3) The material extract had no effect on the content of alkaline phosphatase in the extracellular environment of the two bacteria, but increased the electrical conductivity and potassium ion content in the extracellular environment of the two bacteria. (4) The material extract had no effect on the content of nucleic acid and protein in the extracellular environment of Escherichia coli, and increased the content of nucleic acid and protein in the extracellular environment of Staphylococcus aureus. (5) The material extract could inhibit the nucleic acid content of the two bacteria, but had no effect on the soluble protein content of Escherichia coli cells, and inhibited the synthesis of soluble protein in Staphylococcus aureus cells. (6) Results suggested that Jiao Da Bio-Magnesium porous scaffold material has certain antibacterial properties in vitro, and the inhibitory effect on Staphylococcus aureus is stronger than that on Escherichia coli. The possible antibacterial mechanism is speculated that it can change the permeability of bacterial cell membrane and affect the synthesis of bacterial nucleic acids and proteins. [ABSTRACT FROM AUTHOR]

Bone defect repair has always been a difficult point in clinical treatment. With the development of bone tissue engineering technology and regenerative medicine, scaffolds loaded with active ingredients of traditional Chinese medicine and seed cells and cytokines have become a important issues. In recent years, significant progress has been made in repairing bone defects with bone repair materials containing icariin. It provides a new method for clinical treatment of bone defects. In this paper, the related researches on scaffold materials for bone defect repair with icariin in recent years are summarized. This provides a reference for future research. [ABSTRACT FROM AUTHOR]

Periodontal disease is one of the most common diseases of oral cavity affecting the masses. Conventional therapies of scaling and root planing, GTR, bone grafts were used to restore the lost periodontal tissue. This review article focuses on the application of tissue engineering and scaffold designing in periodontal regeneration and also its development with time. It also talks about the future challenges which need to be addressed by the scientist for the development of innovative biomaterial design. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries (PNIs) are usually caused by trauma, immune diseases, and genetic factors. Peripheral nerve injury (PNI) may lead to limb numbness, muscle atrophy, and loss of neurological function. Although an abundance of theories have been proposed, very few treatments can effectively lead to complete recovery of neurological function. Autologous nerve transplantation is currently the gold standard. Nevertheless, only 50% of all patients were successfully cured using this method. In addition, it causes inevitable damage to the donor site, and available donor sites in humans are very limited. Tissue engineering has become a research hotspot aimed at achieving a better therapeutic effect from peripheral nerve regeneration. Nerve guide conduits (NGCs) show great potential in the treatment of PNI. An increasing number of scaffold materials, including natural and synthetic polymers, have been applied to fabricate NGCs for peripheral nerve regeneration. This review focuses on recent nerve guide conduit (NGC) composite scaffold materials that are applied for nerve tissue engineering. Furthermore, the development tendency of NGCs and future areas of interest are comprehensively discussed.

Prosthetic heart valve replacement is the main treatment for valvular heart disease, but the existing artificial valves (mechanical or biological valve) have inherent disadvantages. Patients with mechanical valves require lifelong anticoagulation because of the high risk of thromboembolism, while the durability of biological valve is poor, which easily leads to calcification or lobular degeneration. Besides, they all lack the abilities of self‐repair and growth which are very important for adolescent patients with valvular heart disease. To overcome these shortcomings, the researchers developed tissue engineered heart valves (TEHV) with self‐repairing and remodeling capabilities, low immunogenicity, and great durability. The preparation of three‐dimensional porous scaffolds is the key step in the success of TEHV. Because of their easy processing, active chemical properties, great mechanical properties and controllable degradation rate, synthetic biodegradable polymers are widely used in the preparation of TEHV scaffolds. This review summarizes the types, properties and process techniques of biodegradable synthetic polymers, such as polycaprolactone, polyglycolic acid, polylactic acid, and polyhydroxyalkanoates currently used to prepare the TEHV scaffolds. This review also focuses on the composite methods and performance of synthetic polymer‐based composite scaffolds. The prospects and challenges of the clinical application for minimally invasive implantation of TEHV are also discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rapid development in tissue engineering research and technology makes dental pulp regeneration and revascularization possible. The interactions of stem cells, scaffolds and signaling factors in tissue engineering are particularly important. Whether stem cells can proliferate, differentiate and develop dental pulp-like tissue greatly depends on the choice of scaffolds OBJECTIVE: To review the widely studied and effective scaffold materials and two methods of scaffold preparation and analyze their applications in dental pulp reconstruction and their revascularization ability. METHODS: The first author searched PubMed, Wanfang and CNKI databases using a computer for relevant articles published between January 1, 2019 and September 30, 2019 with the search terms "pulp regeneration, pulp revascularization, scaffold" in English, and "pulp regeneration, pulp revascularization, revascularization, scaffold" in Chinese. A total of 421 English articles and 181 Chinese articles were retrieved. Finally, 61 articles were reviewed. RESULTS AND CONCLUSION: Platelet-derived scaffolds, extracellular-matrix-derived scaffolds, and self-assembling peptide take effect in pulp regeneration and revascularization. Composite materials combining natural and synthetic materials prepared by hydrogel and nanomaterial techniques exhibited advantages in cell proliferation, differentiation, migration, adherence, anti-inflammation, and factor delivery. The modified composite materials have a strong ability to promote vascularization. With the development of scaffold design and preparation technology based on hydrogels and nanomaterials, problems regarding insufficient scaffold source and unstable clinical effect will be solved in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: The common clinical treatment methods of cardiovascular disease are vascular reconstruction, including stent interventional therapy, coronary artery bypass grafting and angioplasty. OBJECTIVE: To summarize the latest research progress of tissue-engineered vascular stent materials, such as natural derivative stent materials, synthetic macromolecule materials and composite materials, so as to lay a theoretical foundation tor small-caliber vascular transplantation. METHODS: PubMed, WanFang, and CNI databases were retrieved for the articles published from January 2008 to July 2019. The key words were "tissue engineering, biological material, scaffold materiaI, blood vessel" in Chinese and English, respectively. The documents with old content and repasted conclusions were excluded, and 52 eligible articles were enrolled. RESULTS AND CONCLUSION: Autologous vascular grafts, such as saphenous vein and internal thoracic artery, are the best alternatives to small-caliber vessels. However, restenosis of vascular Iumen may be induced after transplantation, and the incidence of thrombosis, infection and transplantation failure increases, which seriously hinders the clinical application. Considering these limitations, researchers have ernbedded tissue-engineered vascular grafts into cells to produce a living material with physiological remodeling activity. This potential solution may bring hope for the future of vascular grafts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Photocross linked alginate hydrogel has been a popular bone tissue engineering material because of its excellent biocompatibility and minimally invasive injection, but there are still problems such as insufficient strength and poor cell adhesion. OBJECTIVE: To construct the negatively charged hydrogels by introducing sodium methacrylate into photocrosslinked alginate hydrogels, and to explore the changes in its physical performance and cell adhesion. METHODS: After preparation of methacrylated alginate by reacting sodium alginate with 2-aminoethyl melhacrylate, methacrylated alginate, photoinitiator and sodium methacrylate (0, 20, 40, 60 mmol/L) were homogeneously mixed. The negatively charged photocrosslinked alginate hydrogels were prepared under ultraviolet light. The functional groups of the hydrogels were analyzed by fourier transform infrared spectroscopy. The surface morphology of the hydrogels was observed by scanning electron microscopy and the swelling ratio was measured. MC3T3-E1 cells were cultured with each group of hydrogels for 48 hours, and the cytotoxicity of the hydrogels was investigated by cell counting kit-8assay. MC3T3-E1 cells were seeded on the surface of each group of hydrogels. The early adhesion of the cells was observed by live/dead staining at the 4th hour, and cell spreading was observed on the 3thday. RESULTS AND CONCLUSION: (1) Fourier transfom infrared spectroscopy demonstrated that the introduction of sodium methacrylate could lead to a new peak at wavenumber of about 1600 cm-1 in the hydrogel infrared wave, which was from the sodium methacrylate. (2) Scanning electron microscope observed that the density of the negatively charged photocrosslinked alginate hydrogels increased and the pore size of the gels decreased with augment of concentrations of sodium methacrylate. (3) The swelling ratio of the hydrogel decreased with the increase of the concentration of sodium methacrylate. (4) The live/dead staining revealed that the cells grew well on the surface of each hydrogel, and the cell viability reached above 95%. The cell counting kit-8 assay results showed that the negatively charged photocrosslinked alginate hydrogels had no cytotoxicity. (5) The early cell adhesion rate increased gradually and the cell extension became better with the increase of concentration of sodium methacrylate. (6) In summary, the introduction of sodium methacryl into pholocrosslinked alginate hydrogels can adjust its physical properties and significantly improve its cell adhesion. [ABSTRACT FROM AUTHOR]

Decellularization involves removal of cellular material from tissue which results in a scaffold material consisting of only the extra cellular matrix (ECM). The effect of each individual decellularizing detergent on the final ECM scaffold and how that may differ from the combined use of these detergents is currently a gap in decellularization methodologies. This study evaluates the hypothesis that a synergistic effect exists when commonly used decellularization detergents are combined. This was evaluated with regard to decellularization efficiency, tissue strength, and collagen structure. Bovine pericardium was decellularized using a combination of 0.5% sodium dodecyl sulfate (SDS), 1% sodium deoxycholate (SDC) and 1% TritonX‐100, and compared to the use of each detergent individually. The combined detergent decellularization protocol showed effective decellularization (p =.004), with minimal effects on tissue strength (p =.21) and structure (p =.21). Use of detergents individually, resulted in detrimental effects on tissue structure and integrity or ineffective decellularization. This study shows a synergistic relationship between SDS, SDC and TritonX‐100 when combined at specific concentrations. The use of detergents in combination instead of individually appears to be superior, as it results in less ECM damage and improved decellularization effectivity. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, there are many types of bone defect repair scaffolds, but a single type of material is difficult to meet the requirements of bone tissue engineering scaffold materials. Several suitable materials can be combined into a composite material by appropriate methods, taking into account the advantages and disadvantages of various materials. It is the focus of scholars in recent years. OBJECTIVE: To construct nano-hydroxyapatite/chitosan/polycaprolactone composite scaffolds and analyze characterization of composite scaffolds. METHODS: Nano-hydroxyapatite/chitosan/polycaprolactone porous ternary composite scaffold material was prepared by 3D printing and molding technology. The characterization of scaffold material was studied from X-ray diffraction analysis, stent water absorption rate, stent compressive strength, stent degradation performance in vitro, stent aperture analysis, scanning electron microscope analysis and other dimensions. RESULTS AND CONCLUSION: (1) X-ray diffraction analysis showed that the crystal-shaped peak map of nano-hydroxyapatite/chitosan/polycaprolactone scaffold materials was similar to the hydroxyapatite powder diffraction standard card, suggesting that the scaffold materials ware integrated with each other through physical interaction, and did not affect the biological function of hydroxyapatite. (2) The average water absorption rate of the scaffold was 18.28%, and the hydrophilicity was good. The maximum pressure that the scaffold could withstand was 1 415 N, and the degradation rate was similar to the osteogenic rate. (3) Under a microscope, a ternary scaffold material with an aperture of 250 μm was successfully produced. The pore size was uniform and distributed regularly. (4) Scanning electron microscope demonstrated that the fibers composed of chitosan and polycaprolactone ware arranged orderly and grid like, hydroxyapatita was distributed uniformly on the fiber surface in granular form, and the ternary composite material presented uniform and loose microporous structure. (5) Nano-hydroxyapatite/chitosan/polycaprolactone ternary composite scaffold material can be successfully prepared through 3D printing and molding technology, which has moderate compressive strength, certain porosity, appropriate degradation rate and water absorption rate, and can lay a foundation for repairing bone defects. [ABSTRACT FROM AUTHOR]

The jawbone is an important component because it functions as a supporting structure of the teeth, regulates mineral homeostasis and protects various organs in the oral cavity.The number of tooth extraction cases in the Oral and Maxillofacial Surgery Clinic of Dental and Oral Hospital, Faculty of Dental Medicine, UniversitasAirlangga average in 2019 every month is 800 teeth. This shows that there is potential to use wasted crowns, such as HA, which will be used as scaffold candidates. Cytotoxicity of HA dental crowns as scaffold candidates will be investigated.Using hidroxyapatite (HA) Powder Preparation and Cytotoxicity Test. The absorbance results for all concentration groups are above 50%, which means HA of dental crowns is not toxic according to CD50, which states the material is said to be toxic if the number of living cells is below 50%. Tooth extraction waste that can be used as HA material is not toxic. [ABSTRACT FROM AUTHOR]

Abstract Over the past years, vascular diseases have continued to threaten human health and increase financial burdens worldwide. Transplantation of allogeneic and autologous blood vessels is the most convenient treatment. However, it could not be applied generally due to the scarcity of donors and the patient’s condition. Developments in tissue engineering are contributing greatly with regard to this urgent need for blood vessels. Tissue engineering-derived blood vessels are promising alternatives for patients with aortic dissection/aneurysm. The aim of this review is to show the importance of advances in biomaterials development for the treatment of vascular disease. We also provide a comprehensive overview of the current status of tissue reconstruction from stem cells and transplantable cellular scaffold constructs, focusing on the combination of stem cells and tissue engineering for blood vessel regeneration and vascular disease treatment.

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BACKGROUND: Bone defect is a common problem encountered in clinical practice. To this end, bone marrow mesenchymal stem cells combined with scaffolds is a hot topic in the treatment of bone defects. OBJECTIVE: To summarize the latest research progress in bone marrow mesenchymal stem cells combined with scaffolds in the treatment of bone defects, which provides a theoretical basis for clinical application. METHODS: The first author searched CNKI, WanFang, VIP, PubMed, Embase and Web of Science databases from January 2009 to December 2018. Search terms were “bone marrow mesenchymal stem cells, isolation, scaffolds, bone defects, bone tissue engineering, osteogenesis, angiogenesis, periosteum, extracellular matrix” in Chinese and English. Totals of 95 articles that met the inclusion criteria were selected. RESULTS AND CONCLUSION: Numerous studies have shown that bone marrow mesenchymal stem cells are ideal seed cells for the treatment of bone defects, and cell-scaffold composites can promote the repair and healing of bone defects. To date, bone marrow mesenchymal stem cells combined with scaffolds as a promising treatment for bone defects have been in the new development era. Great progress has been achieved in terms of isolation, culture and directed differentiation of bone marrow mesenchymal stem cells as well as scaffold materials. These findings further indicate the important roles of new vessels, periosteum and extracellular matrix in bone tissue engineering, which are of great significance for the future clinical treatment of bone defects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preliminary study has shown that inorganic osteogenesis-inducing scaffold material exhibits good biocompatibility and bone-inducing effects in posterior lumbar interbody fusion, with encouraging short-term outcomes. OBJECTIVE: To investigate the safety and long-term effects of inorganic osteogenesis-inducing scaffold materials versus autologous ilium in lumbar interbody fusion. METHODS: This prospective, single-center, non-randomized, controlled trial will include 120 patients who receive treatment for lumbar degenerative diseases at the Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, China. These patients will receive lumbar repair surgery with inorganic osteogenesis-inducing scaffold materials (test group, n=60, 50%) or autologous ilium (control group, n=60, 50%). All patients will be followed up at 1 week, and 1 and 2 years postoperatively. This study was approved by the Medical Ethics Committee, Beijing Tongren Hospital, Capital Medical University, China (approval No. TRECKY2017-158) on September 28, 2017. Study protocol version: 1.0. All participants or their family members must provide written informed consent after fully understanding the study protocol. The study was registered with Chinese Clinical Trial Registry on February 15, 2019 (registration number: ChiCTR1900021333). Study protocol version: 1.0. Patient recruitment bengun and the results will be disseminated through presentations at scientific meetings. RESULTS AND CONCLUSION: The primary outcome measure of this study is the Oswestry Disability Index at 2 years postoperatively. The secondary outcome measures are the Oswestry Disability Index preoperatively and at 1 week and 1 year postoperatively, the Visual Analog Scale score, Japanese Orthopedic Association score, and lumbosacral angle preoperatively and at 1 week, and 1 and 2 years postoperatively, and the incidence of adverse reactions at 1 week, and 1 and 2 years postoperatively. This study will provide evidence to validate whether inorganic osteogenesis-inducing scaffold material results in similar long-term outcomes to autologous ilium in lumbar interbody fusion. [ABSTRACT FROM AUTHOR]

Objective: To construct polyhydroxyalkanoate (PHA) microspheres loaded with bone morphogenetic protein 2 (BMP-2) and human β-defensin 3 (HBD3), and evaluate the antibacterial activity of microspheres and the effect of promoting osteogenic differentiation, aiming to provide a new option of material for bone tissue engineering., Methods: The soybean lecithin (SL)-BMP-2 and SL-HBD3 were prepared by SL-mediated introduction of growth factors into polyesters technology, and the functional microsphere (f-PMS) containing BMP-2 and HBD3 were prepared by microfluidic technology, while pure microsphere (p-PMS) was prepared by the same method as the control. The morphology of microspheres was observed by scanning electron microscopy and the water absorption was detected; the release curves of BMP-2 and HBD3 in f-PMS were detected by ELISA kit. The antibacterial effect of microspheres in Staphylococcus aureus and Escherichia coli was tested with the LIVE/DEAD TM BacLight TM bacterial staining kit; the biocompatibility of microspheres was tested using Transwell and cell counting kit 8 (CCK-8). The effect of microspheres on osteogenic differentiation was determined by collagen type Ⅰ (COL-1) immunofluorescence staining and alkaline phosphatase (ALP) concentration., Results: In this experiment, the f-PMS and p-PMS were successfully constructed. Morphological characteristics showed that p-PMS surface was rough and distributed with micropores of 1-3 μm, while f-PMS surface was smooth and existed white granular material. There was no significant difference in water absorption between the two groups ( P >0.05). The release curves of BMP-2 and HBD3 in the f-PMS and p-PMS were basically the same, showing both early sudden release and late slow release. The antibacterial activity of f-PMS was significantly higher than that of p-PMS in the test that against Staphylococcus aureus and Escherichia coli ( P <0.05), but there was no significant difference in biocompatibility between the two groups ( P >0.05). The results of osteogenic differentiation of human BMSCs showed that the fluorescence intensity of osteogenic specific protein COL-1 of f-PMS was significantly higher than that in p-PMS, and the activity of ALP in f-PMS was also significantly higher than that in p-PMS ( P <0.05)., Conclusion: The p-PHA have good antibacterial activity and biocompatibility, and can effectively promote the osteogenic differentiation of human BMSCs, which is expected to be applied to bone tissue engineering in the future.