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BACKGROUND: How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research. The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE: To investigate the effect of polylactic acid-glycolic acid copolymer (PLGA) composite scaffold modified by lysine-grafted graphene oxide nanoparticles (LGA-g-GO) on osteogenic differentiation and new bone formation. METHODS: PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method. PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution. LGA-g-GO nanoparticles were prepared by chemical grafting method, and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios (1%, 2%, and 3%) with PLGA. The micromorphology, hydrophilicity, and protein adsorption capacity of scaffolds of five groups were characterized. MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION: (1) The surface of PLGA scaffolds was smooth and flat under scanning electron microscope, while the surface of the other four scaffolds was rough. The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles. The water contact angle of PLGA/LGA-g-GO (3%) composite scaffolds was lower than that of the other four groups (P < 0.05). The protein adsorption capacity of PLGA/ LGA-g-GO (1%, 2%, and 3%) composite scaffolds was stronger than PLGA and PLGA/GO scaffolds (P < 0.05). (2) CCK-8 assay showed that PLGA/LGA-g-GO (2%, 3%) composite scaffold could promote the proliferation of MC3T3 cells. Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO (2%, 3%) group was higher than that in the other three groups (P < 0.05). The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO (1%, 2%, and 3%) groups was higher than that in the PLGA group (P < 0.05). (3) In summary, PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts, and is conducive to bone regeneration and bone reconstruction after bone injury. [ABSTRACT FROM AUTHOR]

AbstractLoss of alveolar bone due to periodontitis is prevalent among a wide range of population and is a major concern for oral health. Treatment of alveolar bone loss is aimed based on the repair of the periodontium as well as type of defect that has been formed. Nanocomposite based hydrogel and scaffolds for alveolar bone regeneration has gained significant attention due to their favourable properties such as stability, biocompatibility and enhanced regeneration. Chitin has been used for decades in biomedical applications owing to its good biological activity, biocompatibility and biodegradability. The addition of synthetic polymer such as polydiaxanone into chitin alters the degradation properties and also enhances the biological properties such as osteogenesis. The addition of bioceramic, whitlockite nanoparticles induces mineralization and osteogenesis. Thus, we developed a composite scaffold (Ch-PDO-nWH) using chitin, polydioxanone and whitlockite nanoparticles, a magnesium based bioceramic. The prepared Ch-PDO-nWH composite scaffold is porous in nature, with swelling property and controlled degradation. The scaffold was tested for its biocompatibility using dental follicle stem cells (DFSCs) which showed improved biocompatibility, biomineralization and also stimulated the expression of osteogenic markers such as RUNX2 and OPN thus ultimately aiding in bone regeneration. [ABSTRACT FROM AUTHOR]

Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches are challenging due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a micro-continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60 wt% hydroxyapatite resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite in situ to fit the defect, which is expected to enhance surface contact with surrounding tissue and facilitate biointegration. The antioxidative properties of citrate polymers prevent long-term inflammatory responses. The CSS stimulates osteogenesis in vitro and in vivo. Within 4 weeks in a calvarial critical-sized bone defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Through spatial transcriptomics, we demonstrated the comprehensive biological processes of CSS for prompt osseointegration. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

The development of tissue engineering and regeneration research has created new platforms for bone transplantation. However, the preparation of scaffolds with good fiber integrity is challenging, because scaffolds prepared by traditional printing methods are prone to fiber cracking during solvent evaporation. Human skin has an excellent natural heat-management system, which helps to maintain a constant body temperature through perspiration or blood-vessel constriction. In this work, an electrohydrodynamic-jet 3D-printing method inspired by the thermal-management system of skin was developed. In this system, the evaporation of solvent in the printed fibers can be adjusted using the temperature-change rate of the substrate to prepare 3D structures with good structural integrity. To investigate the solvent evaporation and the interlayer bonding of the fibers, finite-element analysis simulations of a three-layer microscale structure were carried out. The results show that the solvent-evaporation path is from bottom to top, and the strain in the printed structure becomes smaller with a smaller temperature-change rate. Experimental results verified the accuracy of these simulation results, and a variety of complex 3D structures with high aspect ratios were printed. Microscale cracks were reduced to the nanoscale by adjusting the temperature-change rate from 2.5 to 0.5 °C s−1. Optimized process parameters were selected to prepare a tissue engineering scaffold with high integrity. It was confirmed that this printed scaffold had good biocompatibility and could be used for bone-tissue regeneration. This simple and flexible 3D-printing method can also help with the preparation of a wide range of micro- and nanostructured sensors and actuators. ARTICLE HIGHLIGHTS: • A controllable and cost-effective high-resolution E-jet 3d-printing fabrication technology inspired by skin thermal management was developed. • The solvent-evaporation path in the printed structure and its stress–strain development under the influence of temperature were obtained. • High-aspect-ratio 3D structures with good structural integrity were prepared by adjusting the evaporation of the solvent using the temperature-change rate. • A PCL/PVP scaffold with fiber diameters close to the size of living cells was printed, which exhibited high biocompatibility for bone-tissue regeneration. [ABSTRACT FROM AUTHOR]

The challenge of precisely regulating temperature during the photo-thermal bone promotion remains unresolved. Phase change material (PCM), capable of undergoing a phase transition at a specific temperature, offers a solution by photothermal temperature regulation through the storage and release of heat. This study incorporated biocompatible polyethylene glycol (PEG) with specific phase transition points as PCM. A phase change hydrogel scaffold was then synthesized through semi-crosslinking PEG with calcium-ion-chelated sodium alginate (SA) acting as the structural framework. Additionally, the newly developed graphene oxide (GO) modified composite scaffolds (GO-PHSC), featuring 0.5 wt% GO, not only demonstrated outstanding photothermal conversion efficiency and an optimal phase change temperature (42.2 °C) but also exhibited desirable values for latent enthalpy (100 J/g) and latent heat recovered (LHR) (93.3%). Moreover, the form-stability test demonstrated the PCM scaffolds' exceptional resistance to leakage and maintenance of shape stability even at elevated temperatures (70 °C). Beyond achieving passive temperature control in photothermal therapy, experimental findings highlighted that the phase change hydrogel, incorporating calcium ions and GO, met various requirements such as physicochemical properties, microstructure, mechanics, mineralization, biocompatibility, and cell affinity. These collective attributes suggest that GO-PHSC emerges as a promising scaffold composite candidate for temperature-controlled photothermal therapy in bone regeneration.

Scaffold materials, seed cells and growth factors are referred to as the three elements of bone tissue engineering (BTE). However, the physical properties and biocompatibility of these scaffolds and the safety and cost of their growth factors limit their clinical application. Therefore, it is critical to develop a novel scaffold modified with efficient growth factors that meets the requirements of BTE. Herein, 3D-printed poly (lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) composite scaffolds modified with new fusion peptides, which can effectively promote the regeneration and repair of bone defects, were developed. 3D-printed PLGA/HA composite scaffolds with appropriate HA contents were prepared and had appropriate mechanical properties. In addition, the surface of the 3D-printed PLGA/HA composite scaffold was modified with new fusion peptides to provide osteogenic, antimicrobial, and angiogenesis-promoting effects. In vitro experiments showed that the fusion peptide-modified scaffolds had good biocompatibility and a certain degree of antibacterial activity. Moreover, the fusion peptide-modified scaffolds significantly improved the migration ability of BMSCs and Ea.hy926 cells, promoted the expression of osteogenesis-related factors (BMP2, RUNX2, ALP, OPN) in BMSCs, and promoted the expression of angiogenesis-related factors (VEGF and HIF-1α) in Ea.hy926 cells. In vivo experiments showed that the fusion peptide-modified scaffolds had good osteogenic ability. This study reveals considerable application potential for bone defect repair and provides a new option of scaffold material for BTE.

BACKGROUND: The study of the physical properties of scaffolds has always been a hot topic in the field of tissue engineering research. However, for vascular stimulating scaffolds, in addition to meeting the basic performance of the scaffold, other methods are also needed to promote the regeneration of blood vessels within the scaffold, in order to achieve the ultimate goal of repairing bone tissue. OBJECTIVE: A visualization analysis was carried out on the literature published in and outside China on scaffold stimulation for bone tissue engineering, to explore the research hotspots and research status in this field, and to provide a reference for subsequent studies. METHODS: Using the CNKI database and Web of Science core database as retrieval databases, the relevant literature on vascular scaffolds for bone tissue engineering was retrieved. The literature that did not conform to the research object was removed. The obtained data were imported into CiteSpace 6.1.R2 software. Visualization analysis was performed on authors, national institutions, and keywords in the research field. RESULTS AND CONCLUSION: (1) China, the United States, and Germany were the top three countries with the most articles on scaffold stimulation for bone tissue engineering. (2) The top 3 institutions in the CNKI database were Southern Medical University, Huazhong University of Science and Technology, and Donghua University. In the core database of Web of Science, Shanghai Jiao Tong University, Sichuan University and Chinese Academy of Sciences ranked the top 3 in terms of the number of institutional publications. (3) The top 3 keywords in the CNKI database were “tissue engineering, vascularization, angiogenesis”. The top 3 keywords in the Web of Science core database were “mesenchymal stem cell, scaffold, vascularization”. (4) Through the analysis of co-citation and highly cited references, the main concerns were as follows: vascularization strategies: scaffold design, angiogenic factor delivery, in vitro co-culture, and in vivo prevascularization. Technology: 3D printing, electrospinning, vascular transplantation, vascular fusion. Mechanisms: immune regulation and macrophages, drug/ growth factor delivery, the relationship between endothelial cells and osteoblasts, the paracrine relationship between bone cells and endothelial cells, signaling molecular pathways, angiogenesis, and anti-angiogenesis molecules. (5) The researches concerning vascular stimulating scaffolds in bone tissue engineering in and outside China attach great importance to the application of stem cells and 3D printing technology. Current research focuses on biological 3D printing technology, scaffold modification methods, and the development and application of intelligent biomaterials based on bone repair mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: The repair of large-scale bone defects is still facing serious challenges. It is of great significance to develop personalized, low-cost, and osteogenic-inducing tissue engineering scaffolds for bone repair. OBJECTIVE: To explore the process of 3D printing bone tissue engineering scaffold containing pearl composite material by low-temperature condensation deposition method, and further test the physicochemical properties and in vitro biological functions of the composite scaffold. METHODS: Pearl powder was prepared by grinding and sieving. The pearl powder of different qualities was added into the poly-L-lactic acid ink, so that the mass ratio of pearl powder to poly-L-lactic acid was 0, 0.1, 0.2, 0.3, and 0.5, respectively. The 3D-printed poly-L-lactic acid/pearl powder scaffolds were prepared using the low-temperature condensation deposition method. The microstructure, compressive properties, water contact angle, cytocompatibility, and in vitro bone differentiation ability of the printed poly-L-lactic acid/pearl powder composite scaffolds were detected. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the five groups of scaffolds all had micropores with a diameter of 2 μm or even smaller, irregular shapes and interconnectivity. (2) All the five groups had good compressive properties. The compressive strength of the pearl powder 0.5 group was higher than that of the other four groups (P < 0.05). The water contact angle of the pearl powder 0.2 group and the pearl powder 0.5 group was smaller than that of the pearl powder 0 group (P < 0.01, P < 0.001). (3) Bone marrow mesenchymal stem cells were co-cultured with five groups of scaffolds for 1, 3, and 5 days, respectively. The cell proliferation in pearl powder 0.1, 0.2, 0.3, and 0.5 groups cultured for 3 and 5 days was faster than that in pearl powder 0 group (P < 0.05). After 1 day of culture, live-dead staining exhibited that the number of cells on the scaffold was small, but all of them were living cells. (4) Bone marrow mesenchymal stem cells were inoculated on the scaffold surface of the pearl powder 0 group and pearl powder 0.1 group respectively for osteogenic differentiation. The alkaline phosphatase activity induced for 4 and 6 days in the pearl powder 0.1 group was higher than that in the pearl powder 0 group (P < 0.05). (5) The results showed that the poly-L-lactic acid/pearl powder composite scaffold had good compressive strength, hydrophilicity, cytocompatibility, and osteogenic properties. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oral and maxillofacial bone tissue defects can seriously affect the physical and mental health of patients. When bone defects occur in diabetic patients, bone metabolism disorders caused by abnormal blood sugar make it more difficult to repair and treat. OBJECTIVE: To attempt to apply AOPDM1, a polypeptide with potential bioactivity to the osteogenic treatment of diabetic patients. METHODS: In normal or high-glucose environment, different concentrations of AOPDM1 were used to interfere with mouse bone marrow mesenchymal stem cells, and cell proliferation, alkaline phosphatase activity, mineralization nodules formation and osteogenic differentiation gene expression were detected. The polycaprolactone scaffold was prepared by electrospinning technology, and the scaffold was modified by polydopamine to prepare the polycaprolactonepolydopamine composite scaffold. Finally, the scaffolds were placed in AOPDM1 solution to prepare polycaprolactone-polydopamine-AOPDM1 scaffolds. The water contact angle and mechanical properties of the scaffolds were tested in the three groups. In normal or high-glucose environment, the three groups of scaffolds were co-cultured with mouse bone marrow mesenchymal stem cells, respectively, and cell adhesion, alkaline phosphatase activity and osteopontin expression were detected. RESULTS AND CONCLUSION: (1) Compared with normal environment, high-glucose environment inhibited the proliferation of bone marrow mesenchymal stem cells. In the same environment, AOPDM1 could promote the proliferation of mouse bone marrow mesenchymal stem cells. When AOPDM1 concentration was the same, alkaline phosphatase activity, mineralization ability and mRNA expression of type I collagen, osteopontin, alkaline phosphatase, and Runx2 of bone marrow mesenchymal stem cells were decreased in high-glucose environment compared with normal environment. Under the same environment, AOPDM1 could improve the alkaline phosphatase activity, mineralization ability, and mRNA expression of type I collagen, osteopontin, alkaline phosphatase and Runx2 of bone marrow mesenchymal stem cells. (2) The hydrophilicity of polycaprolactone-polydopamine scaffold and polycaprolactone-polydopamineAOPDM1 scaffold was higher than that of polycaprolactone scaffold (P < 0.001), and there was no significant difference in tensile strength and elastic modulus among the three groups (P > 0.05). Compared with the other two groups of scaffolds, the cells on the polycaprolactone-polydopamine-AOPDM1 scaffold had better adhesion morphology. When the scaffolds were identical, compared with normal environment, high-glucose environment inhibited alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells. When the environment was the same, the alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells on the polycaprolactone-polydopamine-AOPDM1 scaffold were higher than those on the other two scaffolds. (3) The above results prove that polycaprolactone-polydopamine-AOPDM composite scaffold can promote the osteogenic properties of bone marrow mesenchymal stem cells in high-glucose environment. [ABSTRACT FROM AUTHOR]

Additive manufacturing has been widely used for producing porous titanium orthopedic implants. However, the higher surface area inherent to porous structures increases the risk of bacterial colonization. In this work, composite scaffolds with dual functions of the antibacterial and osteogenesis promotion properties are developed. The porous titanium is fabricated using a selective laser melting process to provide mechanical support. Silk fibrin (SF) sponge‐loading gentamicin and extracellular vesicles (EVs) are prepared in the pores of the porous titanium. The developed composite scaffolds are investigated for their antibacterial and osteogenesis effects. The samples exhibit well antibacterial activity against Escherichia coli. The samples also show good cytocompatibility, effectively promoting the adhesion and proliferation of the bone marrow mesenchymal stem cells (rBMSCs). EVs significantly promote the expression of osteogenesis‐related genes in rBMCSs and the superior extracellular matrix mineralization reveals that EVs have a remarkable role in enhancing osteogenic differentiation. Therefore, the composite scaffolds with dual functions of antibacterial and osteogenesis promotion properties have excellent potential for orthopedic implant applications. [ABSTRACT FROM AUTHOR]

Natural articular cartilage is a typical self‐healing and superlubrication system capable of maintaining extremely low friction under physiological loadings. Cartilage wear and accidental trauma can cause irreversible defects to cartilage and subchondral bone with a significant decrease in intra‐articular lubrication, leading to the development of severe osteoarthritis and osteochondral defect. To address the important clinical problem of osteochondral defect, a bioinspired hard–soft (PEEK‐lubrication hydrogel) composite scaffold is designed and developed. The polymerization of polyethylene glycol diacrylamide (PEGDAA) and 2‐methacryloyloxyethyl phosphorylcholine (MPC) on polyetheretherketone (PEEK) substrate is achieved by UV initiation to form a strong interfacial bonding, and nano‐hydroxyapatite is deposited on porous PEEK substrate via polydopamine coating to improve osteogenic capability. Accordingly, the composite scaffold is successfully developed with lubrication and osteogenic activity. The tribological tests show that the lubrication performance of the composite scaffold is based on the hydration lubrication mechanism of the upper hydrogel layer, and the in vitro and in vivo experiments demonstrate that the composite scaffold is endowed with excellent biocompatibility and bioactivity. In conclusion, the bioinspired strategy for preparing a hard–soft composite scaffold shows a promising way in the treatment of osteochondral defect and provided a guideline for designing functional PEEK‐based biomaterials in tissue engineering scaffolds. [ABSTRACT FROM AUTHOR]

With the rapid development of materials science and tissue engineering, a variety of biomaterials have been used to construct tissue engineering scaffolds. Due to the performance limitations of single materials, functional composite biomaterials have attracted great attention as tools to improve the effectiveness of biological scaffolds for tissue repair. In recent years, metal-organic frameworks (MOFs) have shown great promise for application in tissue engineering because of their high specific surface area, high porosity, high biocompatibility, appropriate environmental sensitivities and other advantages. This review introduces methods for the construction of MOFs-based functional composite scaffolds and describes the specific functions and mechanisms of MOFs in repairing damaged tissue. The latest MOFs-based functional composites and their applications in different tissues are discussed. Finally, the challenges and future prospects of using MOFs-based composites in tissue engineering are summarized. The aim of this review is to show the great potential of MOFs-based functional composite materials in the field of tissue engineering and to stimulate further innovation in this promising area. [ABSTRACT FROM AUTHOR]

Abstract Natural articular cartilage is a typical self‐healing and superlubrication system capable of maintaining extremely low friction under physiological loadings. Cartilage wear and accidental trauma can cause irreversible defects to cartilage and subchondral bone with a significant decrease in intra‐articular lubrication, leading to the development of severe osteoarthritis and osteochondral defect. To address the important clinical problem of osteochondral defect, a bioinspired hard–soft (PEEK‐lubrication hydrogel) composite scaffold is designed and developed. The polymerization of polyethylene glycol diacrylamide (PEGDAA) and 2‐methacryloyloxyethyl phosphorylcholine (MPC) on polyetheretherketone (PEEK) substrate is achieved by UV initiation to form a strong interfacial bonding, and nano‐hydroxyapatite is deposited on porous PEEK substrate via polydopamine coating to improve osteogenic capability. Accordingly, the composite scaffold is successfully developed with lubrication and osteogenic activity. The tribological tests show that the lubrication performance of the composite scaffold is based on the hydration lubrication mechanism of the upper hydrogel layer, and the in vitro and in vivo experiments demonstrate that the composite scaffold is endowed with excellent biocompatibility and bioactivity. In conclusion, the bioinspired strategy for preparing a hard–soft composite scaffold shows a promising way in the treatment of osteochondral defect and provided a guideline for designing functional PEEK‐based biomaterials in tissue engineering scaffolds.

Covering surgical wounds with biomaterials, biologic scaffolds, and mesenchymal stem cells (MSCs) improves the healing process and reduces postoperative complications. This study was designed to evaluate and compare the effect of MSC-free/MSC-seeded new collagen/poly(3-hydroxybutyrate) (COL/P3HB) composite scaffold and human amniotic membrane (HAM) on the colon anastomosis healing process. COL/P3HB scaffold was prepared using freeze-drying method. MSCs were isolated and characterized from rat adipose tissue. After biocompatibility evaluation by MTT assay, MSCs were seeded on the scaffold and HAM by micro-mass seeding technique. In total, 35 male rats were randomly divided into five groups. After the surgical procedure, cecum incisions were covered by the MSC-free/MSC-seeded scaffold or HAM. Incisions in the control group were only sutured. One month later, the healing process was determined by stereological analysis. The Kruskal-Wallis followed by Dunn's tests were utilized for statistical outcome analysis (SPSS software version 21). COL/10% P3HB scaffold showed the best mechanical and structural properties (7.86 MPa strength, porosity more than 75%). MTT assay indicated that scaffold and especially HAM have suitable biocompatibility. Collagenization and neovascularization were significantly higher, and necrosis was considerably lower in all treated groups in comparison with the controls. MSC-seeded scaffold and HAM significantly decrease inflammation and increase gland volume compared with other groups. The MSC-seeded HAM was significantly successful in decreasing edema compared with other groups. Newly synthesized COL/P3HB scaffold improves the colon anastomosis healing; however, the major positive effect belonged to HAM. MSCs remarkably increase their healing process. Further investigations may contribute to confirming these results in other wound healing. • The novel COL/P3HB composite scaffold has a suitable biocompatibility. • COL/P3HB scaffold and HAM significantly improve the healing of colon anastomosis. • MSCs significantly improve the healing effect of both COL/P3HB scaffold and HAM. • The maintenance condition of COL/P3HB scaffold is simpler (4 °C) than HAM (−80 °C). [ABSTRACT FROM AUTHOR]

The regeneration of bone defects is a major challenge for clinical orthopaedics. Herein, we designed and prepared a new type of bioactive material, using stingray skin collagen and oyster shell powder (OSP) as raw materials. A stingray skin collagen/oyster osteoinductive composite scaffold (Col-OSP) was prepared for the first time by genipin cross-linking, pore-forming and freeze-drying methods. These scaffolds were characterized by ATR-FTIR, SEM, compression, swelling, cell proliferation, cell adhesion, alkaline phosphatase activity, alizarin red staining and RT-PCR etc. The Col-OSP scaffold had an interconnected three-dimensional porous structure, and the mechanical properties of the Col-OSP composite scaffold were enhanced compared with Col, combining with the appropriate swelling rate and degradation rate, the scaffold was more in line with the requirements of bone tissue engineering scaffolds. The Col-OSP scaffold was non-toxic, promoted the proliferation, adhesion, and differentiation of MC3T3-E1 cells, and stimulated the osteogenesis-related genes expressions of osteocalcin (OCN), collagen type I (COL-I) and RUNX2 of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

The healing of bone defects after a fracture remains a key issue to be addressed. Globally, more than 20 million patients experience bone defects annually. Among all artificial bone repair materials that can aid healing, implantable scaffolds made from a mineralized collagen (MC) base have the strongest bionic properties. The MC/PLGA scaffold, created by adding Poly (lactic-co-glycolic acid) copolymer (PLGA) and magnesium metal to the MC substrate, plays a powerful role in promoting fracture healing because, on the one hand, it has good biocompatibility similar to that of MC; on the other hand, the addition of PLGA provides the scaffold with an interconnected porous structure, and the addition of magnesium allows the scaffold to perform anti-inflammatory, osteogenic, and angiogenic activities. Using the latest 3D printing technology for scaffold fabrication, it is possible to model the scaffold in advance according to the requirement and produce a therapeutic scaffold suitable for various bone-defect shapes with less time and effort, which can promote bone tissue healing and regeneration to the maximum extent. This study reviews the material selection and technical preparation of MC/PLGA scaffolds, and the progress of their research on bone defect treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Uneven secretion of matrix and insufficient mechanical strength are important factors affecting the formation effect of tissue engineering constructs in vivo. Mechanical stimulation is an effective means to promote the secretion of extracellular matrix. OBJECTIVE: To explore the biological performance of 3D bioprinted composite scaffolds under mechanical stimulation. METHODS: The chondrocyte-gelatin methacryloyl composite scaffold was prepared and printed by 3D bioprinting technology. Cell survival was observed by live/dead cell staining. The composite scaffolds were placed in a mechanical pressurized bioreactor for pressurized culture. The composite scaffolds cultured in a 6-well plate without pressurization were used as the control. Live/dead cell staining was used to observe the cell survival. Histological staining was used to observe the in vitro cartilage of the composite scaffolds. The relative expression levels of cartilage-related genes were detected by real-time quantitative PCR. The composite scaffolds were implanted into nude mice for 5 weeks in vitro with or without mechanical stimulation, and the cartilage formation was observed by histological staining. RESULTS AND CONCLUSION: (1) The appearance of the composite scaffolds showed a clear grid-like structure. When cultured for 1, 4, and 7 days in vitro, the scaffolds had stable morphology and clear structure, and the cell viability was above 90%. (2) After 2 weeks of culture, the cell survival rate in the composite scaffold in the pressurized group was lower than that in the unpressurized group (P < 0.05). Hematoxylin-eosin staining exhibited that composite scaffolds of the two groups had obvious cartilage lacuna structure, and the cells were distributed evenly in the materials. In the pressurized group, more new cartilage tissue was formed in the gap of the composite scaffold. Safranin O staining showed that red cartilage matrix was formed in both groups; the stained pericellular matrix was deeper in the pressurized group. Type I collagen immunohistochemical staining showed that the coloration in the pressurized group was more obvious; the mRNA expression levels of elastin and type II collagen in the pressurized group were higher than those in the unpressurized group (P < 0.05). (3) After 5 weeks of subcutaneous implantation in nude mice, hematoxylin-eosin staining showed that the formation of cartilage tissue in the pressurized group was more uniform; the size of chondrocytes was uniform; the lacuna structure was obvious. (4) The results show that although in vitro stimulation can trigger cell death in the 3D bioprinted chondrocyte-gelatin methacryloyl composite scaffold, it also promotes the ingrowth of surviving cells into the space of the scaffold and increases the expression of their cartilage matrix-related genes, to promote cartilage formation. [ABSTRACT FROM AUTHOR]

In this research, the Sr‐HA/poly(ɛ‐caprolactone) (PCL) composite scaffold was fabricated using a solvent‐based extrusion method. First, the coprecipitation method was used to synthesize the Sr‐HA powders. For this purpose, strontium was doped into hydroxyapatite (HA) with molar ratios of 0%, 2%, 4%, and 6%. Then, the solvent‐based extrusion method was used to manufacture the 3D printed Sr‐HA/PCL scaffolds. X‐ray diffraction analysis, Fourier transform infrared spectrum, and field emission scanning electron microscope of all samples calcined at 900°C for 1 h indicated the formation of a single‐phase HA structure. The composition of the synthesized powders was confirmed using an inductively coupled plasma test and energy‐dispersive X‐ray spectroscopy. The compressive strength of Sr‐HA/PCL scaffolds compared with pure HA increased from 3.8 to 5.9 MPa. Results of the MTT test showed that Sr‐HA/PCL scaffolds were biocompatible and the growth and proliferation of MG63 cells on the surface of scaffolds increased with the presence of strontium. [ABSTRACT FROM AUTHOR]

Dexiong Li,1,&ast; Jing Xie,1,&ast; Yubei Qiu,1,2 Sihui Zhang,1,3 Jiang Chen1,&ast; 1School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Fujian College and University, Fujian Medical University, Fuzhou, People’s Republic of China; 3Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiang Chen, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China, Tel +86 591 83735488, Fax +86 591 83700838, Email jiangchen@fjmu.edu.cnBackground: Existing implant materials cannot meet the essential multifunctional requirements of repairing infected bone defects, such as antibacterial and osteogenesis abilities. A promising strategy to develop a versatile biomimicry composite of the natural bone structure may be accomplished by combining a multifunctional nanoparticle with an organic scaffold.Methods: In this study, a quaternary ammonium silane-modified mesoporous silica containing nano silver (Ag@QHMS) was successfully synthesized and further combined with silk fibroin (SF) to fabricate the multifunctional nano-reinforced scaffold (SF-Ag@QHMS) using the freeze-drying method. Furthermore, the antibacterial and osteogenic effects of this composite were evaluated in vitro and in vivo.Results: SF-Ag@QHMS inherited a three-dimensional porous structure (porosity rate: 91.90 ± 0.62%) and better mechanical characteristics (2.11 ± 0.06 kPa) than that of the SF scaffold (porosity rate: 91.62 ± 1.65%; mechanic strength: 2.02 ± 0.01 kPa). Simultaneously, the introduction of versatile nanoparticles has provided the composite with additional antibacterial ability against Porphyromonas gingivalis, which can be maintained for 15 days. Furthermore, the expression of osteogenic-associated factors was up-regulated due to the silver ions eluting from the composite scaffold. The in vivo micro-CT and histological results indicated that the new bone formation was not only localized around the border of the defect but also arose more in the center with the support of the composite.Conclusion: The multifunctional silver-loaded mesoporous silica enhanced the mechanical strength of the composite while also ensuring greater and sustained antibacterial and osteogenic properties, allowing the SF-Ag@QHMS composite to be used to repair infected bone defects.Keywords: silk fibroin, quaternary ammonium silane, multifunctional, nano-reinforce, composite scaffold

In this study, we aimed to improve the hydrophilicity, cellular activities and osteogenesis of polycaprolactone (PCL) scaffolds by adding gelatin (Gel) and nano-hydroxyapatite (n-HA). We fabricated biocomposite scaffolds using the extrusion deposition 3 D printing method. The physical and biological properties of the composite scaffold were evaluated. Scanning electron microscopy (SEM) of the fabricated composite scaffolds revealed that the Gel and n-HA particles were uniformly embedded in the internal PCL. The composite scaffold (PCL + Gel + n-HA) showed dramatically improved mechanical properties. The porosity, hydrophilicity and hydrophobicity and ability to promote the attachment and proliferation of osteoblasts were then compared between the pure PCL and composite scaffolds. The PCL + Gel + n-HA scaffold was implanted in the rabbits for 5 weeks, and the results of H&E and Masson staining analyses demonstrated that the scaffold had good biocompatibility and good osteogenesis. The strategy developed in this study has promising prospects for future clinical applications of enhancing bone defect repair. [ABSTRACT FROM AUTHOR]

Biopolymers that mimic the extracellular matrix are favourable in tissue engineering. However, the rapid degradation and the lack of mechanical and enzymatic stabilities of these biopolymers prompt researchers to composite different biopolymers. In this study, we aim to develop an acellular gelatin-chitosan-cellulose nanocrystal (GCCNC) scaffold as a potential wound dressing. The GCCNC mixture was homogenised via ultrasonication and the genipin crosslinking was performed by magnetic stirring. The mixture was then frozen at − 80 °C for 6 h and freeze-dried. The effects of different ratios of gelatin and chitosan with cellulose nanocrystals on the physiochemical properties, mechanical properties, and cellular biocompatibility were studied. Our results herein showed that G3C7CNC demonstrated a homogenous interconnected porous structure with a good porosity (67.37 ± 9.09%) and pore size (148.46 ± 48.68 µm), acceptable swelling ratio (1071.11 ± 140.26%), adequate water vapour transmission rate (315.59 ± 25.27 g/m2/day), low contact angle (70.21 ± 6.79°), and sufficient mechanical strength (modulus of 64.67 ± 12.42 MPa). The lower biodegradation rate in the G3C7CNC (0.06 ± 0.01 mg/hr) compared to G10CNC (0.48 ± 0.07 mg/hr) together with the absence of glass transition phenomenon indicated an increase in both enzymatic and thermal stabilities. Furthermore, G3C7CNC was non-cytotoxic and biocompatible with human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). The presence of collagen type I and α-smooth muscle actin expression in HDFs, together with the expression of cytokeratin-14 in HEKs, demonstrated our scaffold's ability to maintain normal skin physiological functions. Therefore, this study proposes that the fabricated GCCNC scaffold could serve as a potential acellular skin substitute in managing chronic wounds. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, platelet-rich plasma, concentrated growth factors, and 3D-printed nanoscale hydroxyapatite scaffolds have become popular research materials for bone transplantation. At present, the research directions of these materials are scattered, and there are few existing studies targeting large segments of bone and lack of comparison of different types of materials. Because the main component of long diaphysis is cortical bone, its healing is challenging. OBJECTIVE: To evaluate and compare the effects of platelet-rich plasma, concentrated growth factor, and 3D micro-nanostructure composite scaffold on bone defect healing. METHODS: Thirty-two New Zealand white rabbits were enrolled to prepare radial bone defect model of 15 mm. According to the graft, they were divided into four groups (n=8): blank group (no treatment), platelet-rich plasma group (platelet-rich plasma), concentrated growth factor group (concentrated growth factor) and 3D composite scaffold group (3D micro-nanostructure composite scaffold). X-ray examination was performed at 1 day, 6 and 12 weeks postoperatively. Behavioral observation was performed at 12 weeks postoperatively. The rabbit ulnar and radial bone specimens were taken for Micro CT scanning to compare bone mineral density and bone volume fraction. Finally, the bone specimens were sliced and observed under a microscope. RESULTS AND CONCLUSION: (1) The platelet-rich plasma, concentrated growth factor, and 3D composite scaffold groups had different volumes of new bone with little behavioral difference, while the blank group had almost no new bone formation and obvious claudication occurred at 12 weeks after operation. (2) X-ray imaging was better in each intervention group than that in the blank group at 6 and 12 weeks after surgery. The difference in gray values was obvious between the intervention groups, but there was no significant difference between platelet-rich plasma and concentrated growth factor groups at 12 weeks. (3) At 12 weeks after surgery, there was no statistically significant difference in bone mineral density and bone mass between the platelet-rich plasma and concentrated growth factor groups, but all parameters were better than those in the 3D composite scaffold group. (4) It is concluded that undoubtedly plateletrich plasma and concentrated growth factor can promote the early formation of new bone, but there is no significant difference in the long-term effects of platelet-rich plasma and concentrated growth factor. The inorganic scaffold made of hydroxyapatite is difficult to promote the healing of bone defects completely, and other organic components must be added to improve its performance to maximize the osteogenic effect. [ABSTRACT FROM AUTHOR]

The aim of this study was to fabricate and evaluate magnesium-zinc-graphene oxide nanocomposite scaffolds for bone tissue engineering. For this reason, Mg-6Zn, Mg-6Zn-1GO, and Mg-6Zn-2GO scaffolds were fabricated by the powder metallurgy method. The porosity level and also the pore size of the scaffolds were evaluated by SEM which varied from 40 to 46% and 200 to 500 μm, respectively. The chemical composition and microstructure of the scaffolds were characterized by XRD and SEM equipped with EDS; the presence of Mg, Zn, C, and O elements in the structure of the scaffolds was shown. Also, the elemental map confirmed the existence of magnesium, zinc, carbon, and oxygen in the structure of the scaffold. The mechanical properties of the scaffolds were investigated by the compression test; the results showed that by the addition of graphene oxide to the structure, the compressive strength of the samples increased from 5 to 8 MPa. Electrochemical corrosion polarization tests were conducted to evaluate the corrosion resistance of the samples immersed in simulated body fluid (SBF). Furthermore, the biodegradability of the scaffolds was determined by immersion of the samples in phosphate-buffered saline (PBS). The results demonstrated that the polarization resistance value and the corrosion rate for different formulations including Mg-6Zn, Mg-6Zn-1GO, and Mg-6Zn-2GO were 41.58, 35.48, and 55.40 Ω.cm2 followed by 10.60, 14.83, and 9.06 mm.year−1, respectively. Based on the results, the Mg-6Zn-2GO formulation presented the best corrosion resistance among the samples were investigated, which confirmed the results of the immersion test. Moreover, the MTT assay proved that the extract of Mg-6Zn-2GO scaffolds was not cytotoxic in contact with L-929 cells which validated the studied scaffolds for bone tissue applications.

In the current study, we successfully prepared chitosan/gelatin composite scaffolds reinforced by centrifugally spun polylactic acid (PLA) chopped nano/microfibers (PLA-CFs). Herein, different amounts of PLA-CFs (0 %, 1 %, 2 %, 3 %, and 4 % w / v) dispersed in chitosan/gelatin solution were used. Morphological characterization of prepared scaffolds revealed that at the initial stage of adding PLA-CFs, the chopped fibers were localized at the wall of the pores; however, as the fiber load increased, aggregations of chopped-fibers could be seen. Also, mechanical evaluation of scaffolds in terms of compression and tensile mode showed that samples reinforced with 2 % PLA-CFs had enhanced mechanical properties. Indeed, its tensile strength increased from 123.8 to 247.2 kPa for dry and 18.9 to 48.6 kPa for wet conditions. Furthermore, the tensile modulus associated with both conditions increased from 2.99 MPa and 44.5 kPa to 6.43 MPa and 158.4 kPa, respectively. The results of cell culture studies also confirmed that the prepared composite scaffold exhibited appropriate biocompatibility, cell proliferation and migration. The cell infiltration study of the samples revealed that scaffolds reinforced with 2 % PLA-CFs had significantly better cell penetration and distribution compared with the control ones on both days (7 and 14). [Display omitted] • Short PLA nano/micro fibers were obtained using centrifugal spinning/milling method. • Chopped PLA nano/micro fibers were dispersed inside the chitosan/Gelatin hydrogel. • Adding centrifugal-spun nano/micro fibers, enhanced mechanical properties of composite scaffolds specially at wet condition. • Prepared composite scaffolds revealed improved HDF-GFP+ cells bioactivity and infiltration. [ABSTRACT FROM AUTHOR]

The increased number of mastectomies, combined with rising patient expectations for cosmetic and psychosocial outcomes, has necessitated the use of adipose tissue restoration techniques. However, the therapeutic effect of current clinical strategies is not satisfying due to the high demand of personalized customization and the timely vascularization in the process of adipose regeneration. Here, a composite hydrogel scaffold was prepared by three-dimensional (3D) printing technology, applying gelatin methacrylate anhydride (GelMA) as printing ink and calcium silicate (CS) bioceramic as an active ingredient for breast adipose tissue regeneration. The in vitro experiments showed that the composite hydrogel scaffolds could not only be customized with controllable architectures, but also significantly stimulated both 3T3-L1 preadipocytes and human umbilical vein endothelial cells in multiple cell behaviors, including cell adhesion, proliferation, migration and differentiation. Moreover, the composite scaffold promoted vascularized adipose tissue restoration under the skin of nude mice in vivo. These findings suggest that 3D-printed GelMA/CS composite scaffolds might be a good candidate for adipose tissue engineering. [ABSTRACT FROM AUTHOR]

Due to the extreme difficulty of cartilage, we endeavored to fabricate a novel biodegradable scaffold using natural polysaccharide cellulose and poly(lactic-co-glycolic acid) (PLGA) microspheres incorporating controllably released the cartilage inducer kartogenin (KGN) for enhancing regenerative healing in cartilage tissue. Initially, to facilitate the loading of KGN, PLGA/KGN microspheres were fabricated using the solvent volatilization method. These microspheres exhibited high sphericity, with particle sizes diminishing from 12.11 to 3.27 μm as the emulsification rate increased. Demonstrating adequate encapsulation efficiency, the microspheres enabled controlled drug release, positively influencing cell migration and recruitment. Subsequently, a biodegradable cellulose composite scaffold loaded with PLGA/KGN microspheres was prepared using the freeze-drying method. Compared with pure MCC scaffolds, composite scaffolds had a lower degradation rate, and the incorporation of microspheres promoted cell proliferation and significantly elevated expression of cartilage-related specific genes. In a rat cartilage defect model, it was further demonstrated that the composite scaffold combined with stem cell implantation achieved an optimal repair effect, characterized by vigorous extracellular matrix secretion and increased maturity of the regenerated cartilage tissues, suggesting potential clinical application value as a novel articular cartilage repair product in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by joint inflammation and progressive degeneration of articular cartilage. Currently a definitive cure for OA remains to be a challenge due to the very low self-repair capacity of cartilage, thus development of more effective therapies is needed for cartilage repair. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown great potential as therapeutic agents for stimulating regeneration of articular cartilage. However, a standardized protocol is still lacking for manufacturing of highly active EVs for clinical applications. This study aimed to investigate the efficient production of highly active EVs by 3-dimensional (3D) MSC culture, verify the reparative efficacy of EVs on cartilage defect and elucidate the repair mechanisms. Umbilical cord MSCs were embedded in alginate to form MSC spheroids for 3D culture in human platelet lysate (hPL)-containing medium, which produced 3D culture-derived EVs (3D-EVs) with a significantly improved yield. The 3D-EVs expressed higher level of VEGF, and appeared superior to two-dimensional (2D) monolayer MSC culture-derived EVs (2D-EVs) to improve migration and proliferation in MSCs and inflammatory chondrocytes, and to suppress expression of cartilage-degrading factors. Importantly, the 3D-EVs and sodium alginate (SA)-hyaluronic acid (HA) composite hydrogel (3D-EVs/SA-HA) demonstrated significantly improved therapeutic efficacy than 2D-EVs/SA-HA hydrogel for repair of cartilage defect in vivo . The underlying mechanisms are associated with the concomitant upregulation of type II collagen and cartilage synthesis and downregulation of MMP13 in cartilage tissues. Collectively, these data showed that highly active MSC EVs could be efficiently manufactured by 3D cell culture with hPL-containing medium, and these EVs were superior to 2D-EVs for the repair of articular cartilage defect., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Pyrophosphate-stabilized amorphous calcium carbonates (PyACC) are promising compounds for bone repair due to their ability to release calcium, carbonate, and phosphate ions following pyrophosphate hydrolysis. However, shaping these metastable and brittle materials using conventional methods remains a challenge, especially in the form of macroporous scaffolds, yet essential to promote cell colonization. To overcome these limitations, this article describes for the first time the design and multiscale characterization of freeze-cast alginate (Alg)-PyACC nanocomposite scaffolds. The study initially focused on the synthesis of Alg-PyACC powder through in situ coprecipitation. The presence of alginate chains in the vicinity of the PyACC was shown to affect both the powder reactivity and the release of calcium ions when placed in water (XRD, chemical titrations). In vitro cellular assays confirmed the biocompatibility of Alg-PyACC powder, supporting its use as a filler in scaffolds for bone substitutes. In a second step, the freeze-casting process was carried out using these precursor powders with varying rates of inorganic fillers. The resulting scaffolds were compared in terms of pore size and gradient (via SEM, X-ray microtomography, and mercury intrusion porosimetry). All scaffolds exhibited a pore size gradient oriented along the solidification axis, featuring unidirectional, lamellar, and interconnected pores. Interestingly, we found that the pore size and wall thickness could be controlled by the filler rate. This effect was attributed to the in situ cross-linking of alginate chains by released Ca 2+ ions from the fillers, which increased viscosity, affecting temperature-driven segregation during the freezing step. Different multiscale organizations of the porosity and spatial distribution of fillers (FEG-SEM) were correlated with changes in the scaffold mechanical properties (tested via uniaxial compression). With such tunable porous and mechanical properties, Alg-PyACC composite scaffolds present attractive opportunities for specific bone substitute applications.

Although with the good biological properties, silk fibroin (SF) is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties. It is necessary to construct a multifunctional composite scaffold based on SF. In this study, a novel magnetic SF scaffold (MSFCs) was prepared by an improved infiltration method. Compared with SF scaffold (SFC), MSFCs were found to have better crystallinity, magnetocaloric properties, and mechanical strength, which was ascribed to the rational introduction of iron-based magnetic nanoparticles (MNPs). Moreover, in vivo and in vitro experiments demonstrated that the degradation of MSFCs was significantly extended. The mechanism of delayed degradation was correlated with the dual effect that was the newly formed hydrogen bonds between SFC and MNPs and the complexing to tyrosine (Try) to inhibit hydrolase by internal iron atoms. Besides, the β-crystallization of protein in MSFCs was increased with the rise of iron concentration, proving the beneficial effect after MNPS doped. Furthermore, although macrophages could phagocytose the released MNPs, it did not affect their function, and even a reasonable level might cause some cytokines to be upregulated. Finally, in vitro and in vivo studies demonstrated that MSFCs showed excellent biocompatibility and the growth promotion effect on CD34-labeled vascular endothelial cells (VECs). In conclusion, we confirm that the doping of MNPs can significantly reduce the degradation of SFC and thus provide an innovative perspective of multifunctional biocomposites for tissue engineering.

BACKGROUND: Naringin, the active ingredient of Rhizoma Drynariae, has the traditional effect of strengthening the liver and kidney and strengthening the bones and muscles, increasing the thickness of the callus and improving the quality of fracture healing. OBJECTIVE: To explore the bone conduction and bone induction properties of naringin-chitosan/hydroxyapatite composite scaffolds. METHODS: The hydroxyapatite precursor solution with a certain calcium to phosphorus ratio and the chitosan solution containing naringin were crystallized in situ under alkaline conditions and freeze-dried to obtain a naringin-chitosan/hydroxyapatite porous scaffold. A total of 15 SD rats were randomly divided into blank group (n=5), control group (n=5) and experimental group (n=5). The 5 mm-diameter skull bone defect models were established by drilling holes. Biomaterials were not filled in the blank group. Chitosan/hydroxyapatite scaffolds were filled in the control group; and naringin-chitosan/hydroxyapatite scaffolds were filled in the experimental group. At 4 weeks after surgery, CT scans were performed to observe the skull repair. Hematoxylin-eosin staining was used to observe morphological differences. Immunohistochemical staining of bone morphogenetic protein 2 and vascular endothelial growth factor was performed to observe the expression of local osteogenic active factors in the defect areas. RESULTS AND CONCLUSION: (1) CT scan showed that no obvious osteogenesis was seen in the skull of rats in the blank group; only a small amount of new bone was seen at the edge of the defect. In the control group, new bone formation could be seen in the defect pores, and there was less new bone. In the experimental group, the bone defect was well repaired; the density of new bone tissue and the skull around the defect pores were similar, and a large area of new bone widely filled the defect pores. (2) Hematoxylin-eosin staining showed that the defect area in the blank group was filled with thin loose reticular fibrous tissue, and a large number of inflammatory response lesions were seen, and only a small amount of new bone was formed at the edge of the defect. In the control group and the experimental group, residual scaffold material, new bone trabecula and osteoblasts were seen in the defect area; osteoblasts were distributed in clusters in the pores of the scaffold and the edges of the defect area, surrounded by a large number of capillaries. Among them, the experimental group showed a stronger ability of new bone growth. (3) Immuno-histochemical staining showed that the expression levels of local osteogenic activity factors bone morphogenetic protein 2 and vascular endothelial growth factor in the experimental group were higher than those in the control and blank groups (P < 0.05). (4) The results conclude that naringin-chitosan/hydroxyapatite composite scaffolds can provide necessary carrier for bone defect repair. Naringin can create local osteogenic microenvironment, accelerate the growth and mineralization of new bone tissue, and have good bone repair performance. [ABSTRACT FROM AUTHOR]

In the field of bone repair, the inorganic–organic composite scaffold is a promising strategy for mimicking the compositions of the natural bone. In addition, as implants for repairing load-bearing sites, an inert permanent bone substitute composites with bioactive degradable ingredients may make full use of the composite scaffold. Herein, the porous zirconia (ZrO2) matrix was prepared via the template replication method, and the partial degradable ZrO2–chitosan particles–GelMA composite scaffolds with different chitosan/GelMA volume ratios were prepared through the vacuum infiltration method. Dynamic light scattering (DLS) and the scanning electron microscope (SEM) were adopted to observe the size of the chitosan particles and the morphologies of the composites scaffold. The mechanical properties, swelling properties, and degradation properties of the composite scaffolds were also characterized by the mechanical properties testing machine and immersion tests. The CCK-8 assay was adopted to test the biocompatibility of the composite scaffold preliminarily. The results show that chitosan particles as small as 60 nm were obtained. In addition, the ratio of chitosan/GelMA can influence the mechanical properties and the swelling and degradation behaviors of the composites scaffold. Furthermore, improved cell proliferation performance was obtained for the composite scaffolds. [ABSTRACT FROM AUTHOR]

Perfusion culture of mesenchymal stem cells (MSCs) seeded in biomaterial scaffolds provides nutrients for cell survival, enhances extracellular matrix deposition, and increases osteogenic cell differentiation. However, there is no consensus on the appropriate perfusion duration of cellular constructs in vitro to boost their bone forming capacity in vivo. We investigated this phenomenon by culturing human MSCs in macroporous composite scaffolds in a direct perfusion bioreactor and compared their response to scaffolds in continuous dynamic culture conditions on an XYZ shaker. Cell seeding in continuous perfusion bioreactors resulted in more uniform MSC distribution than static seeding. We observed similar calcium deposition in all composite scaffolds over 21 days of bioreactor culture, regardless of pore size. Compared to scaffolds in dynamic culture, perfused scaffolds exhibited increased DNA content and expression of osteogenic markers up to 14 days in culture that plateaued thereafter. We then evaluated the effect of perfusion culture duration on bone formation when MSC-seeded scaffolds were implanted in a murine ectopic site. Human MSCs persisted in all scaffolds at 2 weeks in vivo, and we observed increased neovascularization in constructs cultured under perfusion for 7 days relative to those cultured for 1 day within each gender. At 8 weeks post-implantation, we observed greater bone volume fraction, bone mineral density, tissue ingrowth, collagen density, and osteoblastic markers in bioreactor constructs cultured for 14 days compared to those cultured for 1 or 7 days, and acellular constructs. Taken together, these data demonstrate that culturing MSCs under perfusion culture for at least 14 days in vitro improves the quantity and quality of bone formation in vivo. This study highlights the need for optimizing in vitro bioreactor culture duration of engineered constructs to achieve the desired level of bone formation.

The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro. Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo. The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation (p < 0.05) compared to pure titanium alloy scaffolds in vitro. Furthermore, the composite scaffold can exhibit significant osteogenic differentiation (p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds (p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups (p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration.

The healing of bone defects after a fracture remains a key issue to be addressed. Globally, more than 20 million patients experience bone defects annually. Among all artificial bone repair materials that can aid healing, implantable scaffolds made from a mineralized collagen (MC) base have the strongest bionic properties. The MC/PLGA scaffold, created by adding Poly (lactic-co-glycolic acid) copolymer (PLGA) and magnesium metal to the MC substrate, plays a powerful role in promoting fracture healing because, on the one hand, it has good biocompatibility similar to that of MC; on the other hand, the addition of PLGA provides the scaffold with an interconnected porous structure, and the addition of magnesium allows the scaffold to perform anti-inflammatory, osteogenic, and angiogenic activities. Using the latest 3D printing technology for scaffold fabrication, it is possible to model the scaffold in advance according to the requirement and produce a therapeutic scaffold suitable for various bone-defect shapes with less time and effort, which can promote bone tissue healing and regeneration to the maximum extent. This study reviews the material selection and technical preparation of MC/PLGA scaffolds, and the progress of their research on bone defect treatment.

[Display omitted] • Biocomposite scaffold materials are potential candidates for tissue regeneration. • In this study, the fabricated scaffold was nanostructured utilizing pectin-mediated cerium oxide and egg shell mediated Nano-hydroxyapatite. • The scaffold materials were characterized by using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). • The incorporation of pCeO 2 nanoparticles in the biocomposite scaffold reduce inflammation, thereby promoting tissue healing due to its antioxidant property. • Comprehensive characterization and cytotoxicity studies affirm the biocompatibility of the fabricated scaffold (CS/eHAP/pCeO 2) for tissue engineering applications. In this investigation, composite scaffolds based on chitosan (CS) were created by incorporating egg shell derived hydroxyapatite (eHAP) and pectin-mediated cerium oxide nanoparticles (pCeO 2) as reinforcement. Pectin, a natural polysaccharide facilitates the uniform distribution and stability of CeO₂ nanoparticles within the scaffold. Chitosan (CS), a biopolymer with notable biodegradability and biocompatibility was chosen to provide a supportive matrix for cell growth and differentiation. The CS/eHAP/pCeO₂ scaffolds were fabricated using a freeze-drying technique, resulting in a highly porous structure ideal for cell infiltration and nutrient transport. When pCeO 2 nanoparticles incorporated to bio composite, it reduces inflammation thereby promoting tissue healing due to its antioxidant property. The FT-IR analysis identified the functional groups present in the composite scaffold, while XRD was employed to examine its crystalline nature. Further assessments including SEM imaging for morphology, TGA for thermal stability, DLS and Zeta potential for hydrodynamic radius and surface stability were performed. Notably an increase in pCeO 2 nanoparticles concentration leads to alterations in the crystalline characteristics that is reflected in XRD. The hemolysis assay confirmed the hemocompatibility of the biocomposite scaffold. It was noticed that as the concentration of pCeO 2 nanoparticles increased, there was a remarkable increase in its mechanical properties of the scaffold, conversely this reduced its porosity. In-vitro cell proliferation studies and cytotoxicity of the biocomposite scaffold were done using an NIH/3T3 cell line. The developed CS/eHAP/pCeO₂ scaffold shows a synergistic effect conducive to effective tissue regeneration by the combination of hydroxyapatite's osteo conductivity, cerium oxide's antioxidant properties and chitosan's biocompatibility. These results demonstrate that the concentration of the pCeO 2 nanoparticles additive clearly influences the properties of the biocomposite scaffolds. [ABSTRACT FROM AUTHOR]

BACKGROUND: Composite scaffold has been proven to be effective in treating large segmental bone defects. However, slow bone repair and poor osteogenesis remain to be the main problem. Total flavones of Rhizoma Drynariae can promote osteogenesis and accelerate bone healing, but the route of administration is still confined to intragastric administration and the research about local drug delivery into bone defects is still relatively insufficient. OBJECTIVE: To observe the difference between the local and intragastric administration of total flavones of Rhizoma Drynariae for large segmental bone defects by constructing the scaffold composed of total flavones of Rhizoma Drynariae controlled release microsphere-β-tricalcium phosphate. METHODS: Three-dimensional printing technology was utilized to construct porous β-tricalcium phosphate scaffold. The ultrasonic emulsification solvent dialysis method was used to prepare total flavones of Rhizoma Drynariae sustained-release microspheres. The total flavones of Rhizoma Drynariae sustainedrelease microsphere/β-tricalcium phosphate scaffold was prepared by freeze-drying method. A total of forty SD rats were randomly divided into four groups, and a 3 mm long bone defect model of the tibia was constructed using the circular external fixation. No material was implanted in the bone defect of the blank group, and a simple β-tricalcium phosphate scaffold was placed in the blank scaffold group. A β-tricalcium phosphate scaffold was implanted in the gavage group that was combined with intragastric administration of total flavones of Rhizoma Drynariae, whereas the scaffold composed of total flavones of Rhizoma Drynariae controlled release microsphere-β-tricalcium phosphate was implanted in the drug loaded group. At 8 weeks after operation, imaging test, histological staining, and immunohistochemical staining were conducted. RESULTS AND CONCLUSION: (1) X-ray films and Micro-CT examination showed that there was almost no callus formation in the defect area of the blank group. The callus generated in the blank scaffold group was connected to the osteotomy end, and the osteotomy line was faintly visible. The osteotomy line in the gavage group basically disappeared, and more new bones could be seen connecting both ends of the osteotomy site. In the drug loaded group, a large amount of callus formation was seen; the osteotomy line disappeared completely; the cortex was reconstructed well; and the medullary cavity was recanned. (2) Hematoxylin-eosin, Masson and Safranin Fast Green staining showed that a small amount of blood vessels and a large amount of connective tissue were seen in the defect area of the blank group. More bone matrix formation was seen in the blank scaffold group, but the maturity was not high. In the gavage group, a large amount of bone matrix was formed and mature. In the drug loaded group, a large amount of bone-like tissue was generated in the gap of the osteotomy defect; the cartilage tissue was highly mature, and the medullary cavity was recanalized. (3) Immunohistochemical staining results showed that compared with the blank scaffold group and blank group, transforming growth factor-β and bone morphogenetic protein 2 expression levels were higher in the gavage group and the drug loaded group (P < 0.05). Furthermore, above expression levels were higher in the drug loaded group than those in the gavage group (P < 0.05). (4) The above results indicated that both local administration and intragastric administration of total flavones of Rhizoma Drynariae could promote the repair of bone defects, but a significant difference was observed between the two methods, of which the local administration of controlled release microspheres of total flavones of Rhizoma Drynariae showed better effects. [ABSTRACT FROM AUTHOR]

In this work, physical cross-linking was used to create nanocomposite hydrogels composed of unmodified gum arabic (GA), chitosan (Ch), and natural nanohydroxyapatite (nHA), using an acrylic acid (AA) solvent. Different GA/chitosan contents (15%, 25%, and 35% of the used AA) as well as different nHA contents (2, 5, and 10 wt.%), were used and studied. The natural nHA and the fabricated GA/Ch/nHA nanocomposite hydrogels were characterized using different analysis techniques. Using acrylic acid solvent produced novel hydrogels with compressive strength of 15.43–22.20 MPa which is similar to that of natural cortical bone. The addition of natural nHA to the hydrogels resulted in a significant improvement in the compressive strength of the fabricated hydrogels. In vitro studies of water absorption and degradation—and in vivo studies—confirmed that the nanocomposite hydrogels described here are biodegradable, biocompatible, and facilitate apatite formation while immersed in the simulated body fluid (SBF). In light of these findings, the GA/Ch/nHA nanocomposite hydrogels are recommended for preparing bioactive nanoscaffolds for testing in bone regeneration applications. [ABSTRACT FROM AUTHOR]

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

BACKGROUND: As a common disease of the motor system, bone defect is of great significance to be treated by effective means. However, there is still a lack of literature review on the treatment of bone defect by bibliometrics in China. OBJECTIVE: To analyze the literature on the treatment of bone defect published in recent 10 years and to explore the research status, hotspots, and trends in this field, and to provide opinions and suggestions for its future development. METHODS: Using Web of Science Core Collection database as the data source and the application of bibliometrics, CiteSpace V software was used to draw the knowledge map and conduct cluster analysis of the annual trends, the distribution of nations, the distribution of research institution, the distribution of authors and the key words in the field of bone defect treatment from 2011 to 2020. RESULTS AND CONCLUSION: A total of 1 743 valid articles were selected. (1) The volume of publications shows a steady rise from 2011 to 2020 in general. In terms of scientific research funds, the National Natural Science Foundation of China funded the most projects (23.81%). (2) China and Shanghai Jiao Tong University are the country and research institution with the most publications in this field respectively. USA and Chinese Academy of Sciences play the role of academic hub with the strongest centrality. (3) A total of 476 authors were included. Lei Zhang, Changsheng Liu, and Ana Claudia Muniz Renno were the most prolific researchers, but the core authors did not form a close cooperative relationship. (4) Biomaterials is the journal with the largest number of articles, and has an authoritative position in the field of biological materials. (5) Repair, regeneration, in vitro, scaffold, and mesenchymal stem cell are the research hotspots in this field. (6) Time zone analysis showed that the previous research strategies were mainly for inducing differentiation and promoting regeneration of bone defects. Since 2015, nanoparticles, hydrogels and other materials are gradually widely used in the treatment of bone defects with the help of 3D printing technology. In recent years, researchers hope to explore the mechanism of bone defect treatment at the level of signaling pathway, and hope to use new composite scaffolds combined with drug/growth factor controlled release technology to achieve better therapeutic effect. (7) The future development directions of bone defect treatment are as follows: Continue to prepare new nano-composite scaffolds with good mechanical properties by using 3D printing and other technologies; preparation of double/multiple controlled release drug and/or growth factor stents; repair large bone defects, especially those caused by cancer, while inhibiting inflammation, oxidative stress and other reactions; to explore the mechanism of various growth factors in bone defect repair at the signaling pathway level; basic and clinical research on osteoporosis treatment drugs. It is concluded that bone defect treatment has been paid more and more attention in recent ten years. China has played an important role in this field. The results of this study provide a new perspective for the future research in this field, and play an enlightening role for domestic researchers. [ABSTRACT FROM AUTHOR]

With the development of peripheral nerve tissue engineering, study of biodegradable materials have extensive applied prospect. Chitosan (Cs) is a promising candidate for neural tissue engineering due to its similar chemical structure to glycosaminoglycan. However, due to its lack of elasticity and flexibility, Cs often needs to be used in combination with other materials. In this study, three composite scaffolds were prepared by freeze-drying method: Cs/hyaluronic acid (HA)/gelatin (Gel), Cs/collagen (Col), and Cs/polyethylene glycol (PEG). Mechanical properties, swelling behavior, porosity, and conductivity of these materials have been characterized. Compared with pure Cs, the addition of other materials reduced the average pore size, while improved the mechanical properties of the composite scaffold. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), live/dead staining, cell morphology, and immunofluorescence staining were performed to evaluate the cytotoxicity, biocompatibility, and differentiation of rat pheochromocytoma (PC12) cells on Cs/HA/Gel, Cs/Col, and Cs/PEG composite scaffolds. Our results indicated that all these Cs-based composite scaffolds had good biocompatibility without cytotoxicity, while Cs/PEG scaffolds possessed higher cell survival rate and could promote the adhesion, proliferation, and differentiation of PC12 cells. The Cs-based composite scaffolds developed in this study can serve as promising substitutes for neural tissue regeneration. [ABSTRACT FROM AUTHOR]

The reconstruction of bone defects remains challenging. The utilization of bone autografts, although quite promising, is limited by several drawbacks, especially substantial donor site complications. Recently, strontium (Sr), a bioactive trace element with excellent osteoinductive, osteoconductive, and pro-angiogenic properties, has emerged as a potential therapeutic agent for bone repair. Herein, a strontium peroxide (SrO2)-loaded poly(lactic-co-glycolic acid) (PLGA)-gelatin scaffold system was developed as an implantable bone substitute. Gelatin sponges serve as porous osteoconductive scaffolds, while PLGA not only reinforces the mechanical strength of the gelatin but also controls the rate of water infiltration. The encapsulated SrO2 can release Sr2+ in a sustained manner upon exposure to water, thus effectively stimulating the proliferation of osteoblasts and suppressing the formation of osteoclasts. Moreover, SrO2 can generate hydrogen peroxide and subsequent oxygen molecules to increase local oxygen tension, an essential niche factor for osteogenesis. Collectively, the developed SrO2-loaded composite scaffold shows promise as a multifunctional bioactive bone graft for bone tissue engineering. [ABSTRACT FROM AUTHOR]

In tracheal tissue engineering, the construction of tracheal scaffolds with adequate biodegradable mechanical capacity and biological functions that mimic the structure of a natural trachea is challenging. To explore the feasibility of preparing biomimetic degradable scaffolds with C‐type cartilage rings and an inner tracheal wall of polycaprolactone and silk fibroin. A mold was made according to the diameter of a rabbit trachea, and a silk fibroin tube and polycaprolactone ring attached to the tube were obtained by solution casting. The ring was fixed to the tube at a specific spacing using electrostatic spinning technology to construct a biomimetic tracheal scaffold; its porous structure was observed by scanning electron microscopy, its degradation properties were determined by in vitro enzymatic hydrolysis and its mechanical properties were obtained by pressure testing. The composite scaffold was transplanted subcutaneously into a rabbit model, and the scaffold was taken at 1, 2, and 4 weeks after surgery for sectioning to observe pre‐vascularization. The Medical Ethics Committee of Guangdong Provincial People's Hospital approved the study. The general view of the biomimetic scaffold: the polycaprolactone ring was fixed firmly on the outer wall of the silk fibroin tube; the two corresponded in size, and they fitted closely. The surface of the polycaprolactone ring was smooth and dense, while the surface of the silk fibroin tube could be seen as a uniform porous structure. Scanning electron microscopy showed that the surface and profile of the fibroin tube had a uniform pore size and distribution. The pores were connected to form a network. In vitro, enzymatic hydrolysis experiments confirmed that the fibroin was degraded easily, with most being degraded at the end of week 1. The degradation slowed at 2, 3, and 4 weeks, while the degradation of polycaprolactone was extremely slow. A compression test showed that the compressive resistance of the silk fibroin–polycaprolactone biomimetic scaffolds was much better than that of the rabbit trachea at close thickness. In the tissue staining experiments, as the material degraded, fibrous tissues and blood vessels grew to replace the material, allowing the scaffold to obtain a blood supply and better mechanical properties. A quantitative analysis of CD31 showed that the results for the vascularization of the scaffold were better at 4 weeks than at 2 weeks following subcutaneous grafting (P <.05). The results confirmed that it is feasible to prepare porous, degradable silk fibroin–polycaprolactone biomimetic scaffolds with good mechanical properties and epithelial biological functions by mold casting. [ABSTRACT FROM AUTHOR]

In this study, diopside coated Poly-L-lactic acid-based (PLLA/Diopside) and Poly-L-lactic acid along with pluronic acid (PLLA-P123/Diopside) scaffolds were fabricated by electrospinning to improve the drawbacks with pure polymer and pure bioceramic scaffolds in bone tissue engineering application. The surface morphology, hydrophilicity, and mechanical strength were evaluated. The cell proliferation, differentiation, and expression of osteo related genes were evaluated by measuring the basic osteogenic markers and real time polymerase chain reaction, respectively. Diopside coated Poly-L-lactic acid-based nanofibrous scaffolds have improved surface and biological properties making them a good promising candidate for proliferation and osteogenic differentiation in bone repair and regeneration compared to nanofibrous scaffolds without diopside. Especially, post plasma treated diopside coated PLLA demonstrated better osteogenesis and expression of osteo related genes than the other groups. Although, diopside coated PLLA-P123 composite in comparison with PLLA-Plasma/diopside scaffolds were showed less osteogenesis and expression of osteo related genes, but the results were comparable. Therefore, diopside coated (PLLA-plasma and PLLA/P123 composite) scaffolds could be ideal cost effective grafts in bone repair and replacement therapy. [ABSTRACT FROM AUTHOR]

Delivery of therapeutic peptides via sublingual administration is extremely desired and 3D printed scaffolds are potential candidates as carriers to enhance insulin delivery. 3D printed sublingual sodium alginate (SA)/polyethylene glycol (PEG) composite scaffolds were produced for enhancing insulin delivery by examining the chemical, morphological, mechanical, thermal, cytotoxic, and pharmacokinetic features. The tensile strength and flexibility of scaffolds increased after loading insulin due to the crystalline structure of insulin. Furthermore, insulin-loaded 9SA/3PEG scaffolds showed ultrafast wetting (<1 s), disintegration (<6 s), and also dissolution (<30 s) according to Hixson-Crowell kinetic model. The cell viability of L929 cells on 3D printed scaffolds was examined and these scaffolds could be safely applied on animals. Pharmacokinetic parameters and blood glucose level were evaluated following sublingual administration of scaffolds to type-1 diabetic rats. A single dose of scaffold presented a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min and it lasted for 12 h by increasing the bioavailability of insulin. Scaffolds indicated a sustained profile for serum insulin levels, which continued to increase slightly after 3 h during the study. The polymeric scaffold with a high safety and efficacy holds a new promising delivery strategy for administering injectable insulin through the sublingual route. [Display omitted] • Sodium alginate/polyethylene glycol scaffolds were produced by 3D printing. • Scaffolds were used as carriers to enhance insulin delivery via sublingual route. • Ultrafast wetting, disintegration (<6 s), and dissolution (<30s) were presented. • Scaffolds show a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min. • Scaffolds indicated a sustained profile for serum insulin levels lasted for 12 h. [ABSTRACT FROM AUTHOR]

Mussel-derived nacre and pearl, which are natural composites composed CaCO3 platelets and interplatelet organic matrix, have recently gained interest due to their osteogenic potential. The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls. So far, little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl. In the current work, aragonite or vaterite pearl powders were incorporated into poly-l-lactic acid (PLLA) scaffold as bio-functional fillers for enhanced osteogenesis. In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation, evidenced by the enhanced cell viability, alkaline phosphatase activity, collagen synthesis and gene expressions of osteogenic markers including osteocalcin, osteopotin and bone sialoprotein. The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model. The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds, while less bone formation and non-bridging were found for pure PLLA group. Histological evaluation using Masson's trichrome and hematoxylin/eosin (H&E) staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds. Through three-point bending test, the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups. Together, it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.

Qinghui Zhao1 12 23 3,* Hongming Tang1 12 23 3,* Lishu Ren4 4, Jie Wei4 4 1School of Life Sciences and Technology, Tongji University, Shanghai 200092, People’s Republic of China; 2Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, People’s Republic of China; 3Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200123, People’s Republic of China; 4Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinghui Zhao Tel +86-21-38804518Email qinghui_zhao@126.comPurpose: A bioactive and degradable scaffold of ternary composite with good biocompatibility and osteogenesis was developed for bone tissue repair.Materials and Methods: Polybutylene succinate (PS:50 wt%), magnesium phosphate (MP:40 wt%) and wheat protein (WP:10 wt%) composite (PMWC) scaffold was fabricated, and the biological performances of PMWC were evaluated both in vitro and vivo in this study.Results: PMWC scaffold possessed not only interconnected macropores (400 μm to 600 μm) but also micropores (10 μm ∼ 20 μm) on the walls of macropores. Incorporation of MP into composite improved the apatite mineralization (bioactivity) of PMWC scaffold in simulated body fluid (SBF), and addition of WP into composite further enhanced the degradability of PMWC in PBS compared with the scaffold of PS (50 wt%)/MP (50 wt%) composite (PMC) and PS alone. In addition, the PMWC scaffold containing MP and WP significantly promoted the proliferation and differentiation of mouse pre-osteoblastic cell line (MC3T3-E1) cells. Moreover, the images from synchrotron radiation microcomputed tomography (SRmCT) and histological sections of the in vivo implantation suggested that the PMWC scaffold containing MP and WP prominently improved the new bone formation and ingrowth compared with PMC and PS. Furthermore, the immunohistochemical analysis further confirmed that the PMWC scaffold obviously promoted osteogenesis and vascularization in vivo compared with PMC and PS.Conclusion: This study demonstrated that the biocompatible PMWC scaffold with improved bioactivity and degradability significantly promoted the osteogenesis and vascularization in vivo, which would have a great potential to be applied for bone tissue repair.Keywords: polybutylene succinate, composite scaffold, cytocompatibility, osteogenesis, vascularization