Scaffolds For Bone Tissue Engineering Research Articles

Fabrication and characterizations of simvastatin-containing mesoporous bioactive glass and molybdenum disulfide scaffold for bone tissue engineering.

Due to the limitations of the current treatment approaches of allograft and autograft techniques, treating bone disorders is a significant challenge. To address these shortcomings, a novel biomaterial composite is required. This study presents the preparation and fabrication of a novel biomaterial composite scaffold that combines poly (D, L-lactide-co-glycolide) (PLGA), mesoporous bioactive glass (MBG), molybdenum disulfide (MoS2), and simvastatin (Sim) to address the limitations of current bone grafting techniques of autograft and allograft. The fabricated scaffold of PLGA-MBG-MoS2-Sim composites was developed using a low-cost hydraulic press and salt leaching method, and scanning electron microscopy (SEM) analysis confirmed the scaffolds have a pore size between 143 and 240 μm. The protein adsorption for fabricated scaffolds was increased at 24 h. The water adsorption and retention studies showed significant results on the PLGA-MBG-MoS2-Sim composite scaffold. The biodegradation studies of the PLGA-MBG-MoS2-Sim composite scaffold have shown 54% after 28 days. In vitro, bioactivity evaluation utilizing simulated body fluid studies confirmed the development of bone mineral hydroxyapatite on the scaffolds, which was characterized using x-ray diffraction, Fourier transform infrared, and SEM analysis. Furthermore, the PLGA-MBG-MoS2-Sim composite scaffold is biocompatible with C3H10T1/2 cells and expresses more alkaline phosphatase and mineralization activity. Additionally, in vivo research showed that PLGA-MBG-MoS2-Sim stimulates a higher rate of bone regeneration. These findings highlight the fabricated PLGA-MBG-MoS2-Sim composite scaffold presents a promising solution for the limitations of current bone grafting techniques.

Macroporous Nanostructured Calcium Phosphate/Chitosan-Gelatin Composite Bone Tissue Engineering Scaffold

Background: Tissue engineering is an emerging technology developed for the therapeutic reconstruction of damaged tissue. Objective: In this study, a ceramic/polymer nanocomposite bone tissue engineering scaffold was prepared by coating a tetracalcium phosphate/dicalcium phosphate mixture slurry on a porous 3D chitosan-gelatin construction. Methods: The phase composition, structural groups, and morphological aspects of the samples were characterized. Furthermore, the 3D composite scaffold was immersed in simulated body fluid (SBF) solution at 37ºC for various periods to track its compositional and structural changes. Results: Based on the results, the coated layer is composed of needle-like carbonated apatite nanosized crystals with some tetracalcium phosphate/dicalcium phosphate initial materials. The nanocomposite was porous with an average macropore size of about 410 μm. The in vitro tests revealed that the composition of the coated layer tends to be apatite crystals, which are similar to natural bone in terms of chemistry and morphology. Conclusion: The results suggest that a simple coating of chitosan-gelatin scaffolds using reactive calcium phosphate particles may introduce a novel nanocomposite scaffold with improved mechanical strength, bioactivity, and osteoconductivity.

Controlled drug release from policaprolactone-piperine electrospun scaffold for bone tissue engineering

Polymeric drug scaffolds have been intensively studied in orthopedic surgery due to their capacity for the regimented and site-specific liberation of the therapeutic agent at the intended locus. In this context, electrospinning is a promising technique for producing scaffolds using biodegradable and biocompatible polymers. In the present study, scaffolds of Polycaprolactone (PCL) with Piperine (PIP) incorporated at different concentrations (1, 3, and 5 %) were obtained by electrospinning. The electrospun PCL, PCL/PIP 1 %, PCL/PIP 3 %, and PCL/PIP 5 % groups were analyzed by FTIR spectroscopy to identify the incorporated drug and through UV-VIS spectroscopy to evaluate its controlled release. In addition, the bone repair was verified by Raman spectroscopy using ᶹ1PO43- vibration data obtained by in vivo analysis. The morphology and diameter of the nanofibers were obtained by scanning electron microscopy (SEM). The PCL, PCL/PIP 1 %, PCL/PIP 3 %, PCL/PIP 5 % scaffolds had diameters of 0.0015 ± 0.002 μm, 1.08 ± 0.007 μm, 1.09 ± 0.02 μm, 0.59 ± 0.016 μm, respectively. Piperine release was pronounced after 15 days. Therefore, at 30 days, the PCL/PIP 1 % scaffold released 64 % ± 0.00062, while the PCL/PIP 3 % and PCL/PIP 5 % scaffolds released only 16.06 ± 0.00012 and 9.08 % ± 0.00031, respectively. This study provided evidence that PCL/Piperine can be used to significantly increase bone regeneration. Results from Raman spectroscopy and histological analysis demonstrated that the PCL/PIP 1 %, 3 %, and 5 % groups had better bone regeneration than the negative control group after 15 days and 30 days of treatment. The prolonged release of piperine promoted by PCL, a hydrophobic drug carrier, caused the neoformation of the bones to be restricted to the inner part of the bone defect, creating an immature bone with evident cellular differentiation.

Advances in the Application of Photothermal Composite Scaffolds for Osteosarcoma Ablation and Bone Regeneration.

Photothermal therapy is a promising approach to cancer treatment. The energy generated by the photothermal effect can effectively inhibit the growth of cancer cells without harming normal tissues, while the right amount of heat can also promote cell proliferation and accelerate tissue regeneration. Various nanomaterials have recently been used as photothermal agents (PTAs). The photothermal composite scaffolds can be obtained by introducing PTAs into bone tissue engineering (BTE) scaffolds, which produces a photothermal effect that can be used to ablate bone cancer with subsequent further use of the scaffold as a support to repair the bone defects created by ablation of osteosarcoma. Osteosarcoma is the most common among primary bone malignancies. However, a review of the efficacy of different types of photothermal composite scaffolds in osteosarcoma is lacking. This article first introduces the common PTAs, BTE materials, and preparation methods and then systematically summarizes the development of photothermal composite scaffolds. It would provide a useful reference for the combination of tumor therapy and tissue engineering in bone tumor-related diseases and complex diseases. It will also be valuable for advancing the clinical applications of photothermal composite scaffolds.

Integrating Fluorescence and Magnetic Resonance Imaging in Biocompatible Scaffold for Real-Time Bone Repair Monitoring and Assessment.

In situ monitoring of bone tissue regeneration progression is critical for the development of bone tissue engineering scaffold. However, engineered scaffolds that can stimulate osteogenic progress and allow for non-invasive monitoring of in vivo bone regeneration simultaneously are rarely reported. Based on a hard-and-soft integration strategy, a multifunctional scaffold composed of 3D printed microfilaments and a hydrogel network containing simvastatin (SV), indocyanine green-loaded superamphiphiles, and aminated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NH2 ) is fabricated. Both in vitro and in vivo results demonstrate that the as-prepared scaffold significantly promotes osteogenesis through controlled SV release. The biocomposite scaffold exhibits alkaline phosphatase-responsive near-infrared II fluorescence imaging. Meanwhile, USPIO-NH2 within the co-crosslinked nanocomposite network enables the visualization of scaffold degradation by magnetic resonance imaging. Therefore, the biocomposite scaffold enables or facilitates non-invasive in situ monitoring of neo-bone formation and scaffold degradation processes following osteogenic stimulation, offering a promising strategy to develop theranostic scaffolds for tissue engineering.

Bone-like apatite formation in biocompatible phosphate-crosslinked bacterial cellulose-based hydrogels for bone tissue engineering applications

Addressing major bone injuries is a challenge in bone regeneration, necessitating innovative 3D hydrogel-based therapeutic approaches to enhance scaffold properties for better bioactivity. Bacterial cellulose (BC) is an excellent scaffold for bone tissue engineering due to its biocompatibility, high porosity, substantial surface area, and remarkable mechanical strength. However, its practical application is limited due to a lack of inherent osteogenic activity and biomineralization ability. In this study, we synthesized bone-like apatite in biocompatible BC hydrogel by introducing phosphate groups. Hydrogels were prepared using fibrous BC, acrylamide (AM), and bis [2-methacryloyloxy] ethyl phosphate (BMEP) as a crosslinker through free radical polymerization (P-BC-PAM). P-BC-PAM hydrogels exhibited outstanding compressive mechanical properties, highly interconnected porous structures, good swelling, and biodegradable properties. BMEP content significantly influenced the physicochemical and biological properties of the hydrogels. Increasing BMEP content enhanced the fibrous structure, porosity from 85.1 % to 89.5 %, and compressive mechanical strength. The optimized hydrogel (2.0P-BC-PAM) displayed maximum compressive stress, toughness, and elastic modulus at 75 % strain: 221 ± 0.08 kPa, 24,674.2 ± 978 kPa, and 11 ± 0.47 kPa, respectively. P-BC-PAM hydrogels underwent biomineralization in simulated body fluid (SBF) for 14 days, forming bone-like apatite with a Ca/P ratio of 1.75, similar to hydroxyapatite. Confirmed by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and field-emission scanning electron microscopy (FE-SEM), this suggests their potential as scaffolds for bone tissue engineering. MC3T3-E1 osteoblast cells effectively attached and proliferated on P-BC-PAM. In summary, this study contributes insights into developing phosphate-functionalized BC-based hydrogels with potential applications in bone tissue engineering.

Recent advances of responsive scaffolds in bone tissue engineering.

The investigation of bone defect repair has been a significant focus in clinical research. The gradual progress and utilization of different scaffolds for bone repair have been facilitated by advancements in material science and tissue engineering. In recent times, the attainment of precise regulation and targeted drug release has emerged as a crucial concern in bone tissue engineering. As a result, we present a comprehensive review of recent developments in responsive scaffolds pertaining to the field of bone defect repair. The objective of this review is to provide a comprehensive summary and forecast of prospects, thereby contributing novel insights to the field of bone defect repair.

Elastic 3D-Printed Nanofibers Composite Scaffold for Bone Tissue Engineering.

Loading nanoparticles into hydrogels has been a conventional approach to augment the printability of ink and the physicochemical characteristics of scaffolds in three-dimensional (3D) printing. However, the efficacy of this enhancement has often proven to be limited. We amalgamate electrospun nanofibers with 3D printing techniques to fabricate a composite scaffold reminiscent of a "reinforced concrete" structure, aimed at addressing bone defects. These supple silica nanofibers are synthesized through a dual-step process involving high-speed homogenization and low-temperature ball milling technology. The nanofibers are homogeneously blended with sodium alginate to create the printing ink. The resultant ink was extruded seamlessly, displaying commendable molding properties, thereby yielding scaffolds with favorable macroscopic morphology. In contrast to nanoparticle-reinforced scaffolds, composite scaffolds containing nanofibers exhibit superior mechanical attributes and bioactivity. These nanofiber composite scaffolds demonstrate enhanced osteoinductive properties in both in vitro and in vivo evaluations. To conclude, this research introduces a novel 3D printing approach where the fabricated nanofiber-infused 3D-printed scaffolds hold the potential to revolutionize the realm of 3D printing in the domain of bone tissue engineering.

Effects of cerium-doped bioactive glass incorporation on an alginate/gelatin scaffold for bone tissue engineering: In vitro characterizations

Bioactive glasses (BGs) have been extensively employed in treating bone defects due to their capacity to bond and integrate with hard and soft tissues. To promote their characteristics, BGs are doped with therapeutic inorganic ions; Among these, Cerium (Ce) is of special attention because of its material and biological properties. This study aimed to investigate the effects of the addition of Ce to BG on the physicochemical and biological properties of the alginate/gelatin (Alg-Gel) scaffold compared with a similar scaffold that only contains BG45S5. The scaffolds were characterized for their biocompatibility using human bone marrow-derived mesenchymal stem cells (hBM-MSCs) by MTT analysis. The osteogenic differentiation of hBM-MSCs cultured on the scaffolds was assessed by evaluating the alkaline phosphatase (ALP) activity and the expression of osteogenic-related genes. Scanning electron microscopy of the prepared scaffolds showed an interconnected porous structure with an average diameter of 212–272 μm. The Young's modulus of the scaffolds significantly increased from 13 ± 0.82 MPa for Alg-Gel to 91 ± 1.76 MPa for Alg-Gel-BG/Ce. Ce doping improved the osteogenic differentiation of hBM-MSCs and ALP secretion compared to the other samples, even without adding an osteogenic differentiation medium. The obtained results demonstrated the biocompatibility and osteo-inductive potentials of the Alg-Gel-BG/Ce scaffold for bone tissue engineering.

Effects of Gamma Irradiation on the Properties of Hydroxyapatite-Collagen-Chitosan-Mg-ZnO Scaffolds for Bone Tissue Engineering

Bone tissue engineering aims to repair diseased or damaged bone that cannot be regenerated naturally. This study is designed to develop biodegradable porous scaffolds as bone substitutes and evaluate the effect of gamma irradiation on these scaffolds for the restoration of defected bone. Here, composite scaffolds (HA-COL-CS-Mg-ZnO) were prepared by the thermally induced phase separation (TIPS) technique using collagen (COL) and chitosan (CS), hydroxyapatite (HA), magnesium (Mg), and zinc oxide (ZnO) at different mass ratios. Thereafter, the scaffolds were subjected to 10 KGy γ-radiation for physical cross-linking and sterilization. The physicochemical and biological properties of the scaffolds were evaluated by Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), field emission scanning electron microscopy (FESEM), physical stability (biodegradability, swelling rate, porosity, and density), mechanical properties, biocompatibility, cytotoxicity, and antimicrobial activity against Escherichia coli (ATCC-25922) and Staphylococcus aureus (ATCC-25923). We found that the irradiated scaffold showed enhanced tensile strength and antimicrobial activities which are desirable characteristics of bone-mimicking scaffolds. FESEM revealed that the average pore size decreased from 192.3 to 104.5 μm due to radiation. FTIR-ATR spectra showed that γ-radiation triggered cross-linking in the polymer matrix which improved mechanical strength (0.82 N/mm2 to 1.86 N/mm2) by increasing pore wall thickness. Moreover, the irradiated and nonirradiated scaffolds were biocompatible and noncytotoxic toward the Vero cell line which ensured their suitability for use in vivo. These results demonstrate that sterilization of HA-COL-CS-Mg-ZnO scaffolds with gamma-irradiation substantially improves the physicochemical and morphological features which aid bone tissue regeneration and could be supportive for new bone formation.

Preparation and Characterization of Freeze-Dried β-Tricalcium Phosphate/Barium Titanate/Collagen Composite Scaffolds for Bone Tissue Engineering in Orthopedic Applications

The freeze-drying method creates a scaffold with a composite mesoporous structure with many advantages. However, everyday materials such as β-tricalcium phosphate (β-TCP) have been used as an orthopedic implant for canine tribal bone defects for decades, for instance, for grafting material of even shapes to form an implant for our teeth. However, this material is still not entirely expected to be the best implant due to its high biodegradability. Besides that, using the piezoelectric effect on the bone can lead to more efficiency in cell growth and a faster healing time for patients. Based on this phenomenon, a scaffold composite with a piezoelectric material such as barium titanate (BaTiO3/BT) has been tested. Based on the BT/β-TCP ratio, the scaffold composite of BT and β-TCP produces a porous structure with porosity ranging from 30.25 ± 11.28 to 15.25 ± 11.28 μm. The BT/β-TCP ratio influences the samples’ pore type, which affects each sample’s mechanical properties. In our result, the scaffold of 45.0 wt% BT/45.0 wt% β-TCP/10.0 wt% collagen has achieved a significant value of 0.5 MPa for maximum stress with a sufficient pore size of 25.32 ± 8.05 μm. Finally, we performed a viability test to see the sample’s piezoelectric effect, which showed that the piezoelectric effect does increase bone healing time when tested by growing MC3T3-E1 cells on the samples.

Curcumin and resveratrol delivery from multi-functionalized calcium phosphate scaffold enhances biological properties

Natural medicinal compounds (NMCs) can assist effectively in treating bone disorders. NMC release kinetics from a ceramic bone tissue engineering scaffold can be tailored. However, inferior physicochemical properties halt their therapeutic applications and need a carrier system for delivery. We developed a multi-functionalized scaffold to understand the effect of curcumin (Cur) and resveratrol (Rsv) on in vitro biological properties. Polycaprolactone (PCL) nanoparticles encapsulated resveratrol in the polymeric matrix. Nanoparticles showed a hydrodynamic diameter of about 180 nm, −16 mV zeta potential, and up to ∼65 % encapsulation efficiency. Scaffolds made of zinc-doped tricalcium phosphate (Zn-TCP) were coated with curcumin followed by either resveratrol (Cur-Rsv) or resveratrol nanoparticles (Cur-Rsv-NP). NMC-loaded scaffolds exhibited a biphasic release pattern over 60 days. Solubility and hydrophobic-hydrophilic interactions affected the NMC release profile. Resveratrol showed rapid release as compared to curcumin. The treated scaffold increased the cell viability of human fetal osteoblast (hFOB) by 1.8-fold as compared to the control. It exhibited a 6-fold increase in cytotoxicity toward osteosarcoma (MG-63) cells as compared to the untreated scaffold. NMCs loaded scaffold effectively inhibited Staphylococcus aureus from colonizing over the scaffold. Zinc doping enhanced osteoblast growth and prevented bacterial colony formation. Such design principle provided a direction for developing multi-functionalized calcium phosphate (CaP) scaffolds against bone diseases for orthopedic applications.

Towards Polycaprolactone-Based Scaffolds for Alveolar Bone Tissue Engineering: A Biomimetic Approach in a 3D Printing Technique.

The alveolar bone is a unique type of bone, and the goal of bone tissue engineering (BTE) is to develop methods to facilitate its regeneration. Currently, an emerging trend involves the fabrication of polycaprolactone (PCL)-based scaffolds using a three-dimensional (3D) printing technique to enhance an osteoconductive architecture. These scaffolds are further modified with hydroxyapatite (HA), type I collagen (CGI), or chitosan (CS) to impart high osteoinductive potential. In conjunction with cell therapy, these scaffolds may serve as an appealing alternative to bone autografts. This review discusses research gaps in the designing of 3D-printed PCL-based scaffolds from a biomimetic perspective. The article begins with a systematic analysis of biological mineralisation (biomineralisation) and ossification to optimise the scaffold's structural, mechanical, degradation, and surface properties. This scaffold-designing strategy lays the groundwork for developing a research pathway that spans fundamental principles such as molecular dynamics (MD) simulations and fabrication techniques. Ultimately, this paves the way for systematic in vitro and in vivo studies, leading to potential clinical applications.

Silver-doped hydroxyapatite laden chitosan–gelatin nanocomposite scaffolds for bone tissue engineering: an in-vitro and in-ovo evaluation

Despite the advancements in bone tissue engineering, the majority of implant failures are caused due to microbial contamination. So, efforts are being made to develop biomaterial with antimicrobial property enhancing the regeneration of damaged bone tissue. In the present study, chitosan–gelatin (CG) scaffolds containing silver-doped hydroxyapatite (AgHAP) nanoparticles at 0.5%, 1.0% and 1.5% (w/v) were fabricated by lyophilization technique. The results confirmed the synthesis of AgHAP nanoparticles and showed interconnected porous structure of the nanocomposite scaffolds with 89%–75% porosity. Similarly, the swelling percentage, degradation behavior and compressive modulus of CG-AgHAP nanocomposite scaffolds were 1666%, 40% and 0.7 MPa, respectively. The developed nanocomposite scaffolds revealed better antimicrobial properties and bioactivity. The cell culture studies showed favorable viability of Wharton’s jelly stem cells on CG-AgHAP nanocomposite scaffolds. CAM (chorioallantoic membrane) assay determined the angiogenic potential with better visualization of blood vessels in the CAM area. Hence, the obtained results confirmed that CG-AgHAP3 nanocomposite scaffold was the most suitable for bone tissue engineering applications among all scaffolds.

Resorbable GBR Scaffolds in Oral and Maxillofacial Tissue Engineering: Design, Fabrication, and Applications.

Guided bone regeneration (GBR) is a promising technique in bone tissue engineering that aims to replace lost or injured bone using resorbable scaffolds. The promotion of osteoblast adhesion, migration, and proliferation is greatly aided by GBR materials, and surface changes are critical in imitating the natural bone structure to improve cellular responses. Moreover, the interactions between bioresponsive scaffolds, growth factors (GFs), immune cells, and stromal progenitor cells are essential in promoting bone regeneration. This literature review comprehensively discusses various aspects of resorbable scaffolds in bone tissue engineering, encompassing scaffold design, materials, fabrication techniques, and advanced manufacturing methods, including three-dimensional printing. In addition, this review explores surface modifications to replicate native bone structures and their impact on cellular responses. Moreover, the mechanisms of bone regeneration are described, providing information on how immune cells, GFs, and bioresponsive scaffolds orchestrate tissue healing. Practical applications in clinical settings are presented to underscore the importance of these principles in promoting tissue integration, healing, and regeneration. Furthermore, this literature review delves into emerging areas of metamaterials and artificial intelligence applications in tissue engineering and regenerative medicine. These interdisciplinary approaches hold immense promise for furthering bone tissue engineering and improving therapeutic outcomes, leading to enhanced patient well-being. The potential of combining material science, advanced manufacturing, and cellular biology is showcased as a pathway to advance bone tissue engineering, addressing a variety of clinical needs and challenges. By providing this comprehensive narrative, a detailed, up-to-date account of resorbable scaffolds' role in bone tissue engineering and their transformative potential is offered.

GelMA-catechol coated FeHAp nanorods functionalized nanofibrous reinforced bio-instructive and mechanically robust composite hydrogel scaffold for bone tissue engineering

Critical bone defects complicate tissue graft-based surgeries, raising healthcare expenditures and underscoring scaffold-based tissue-engineering strategies to support bone reconstruction. Our study highlighted that the phase-compatible combination of inorganic nanorods, nanofibers, and hydrogels is promising for developing biomimetic and cell-instructive scaffolds since the bone matrix is a porous organic/inorganic composite. In brief, methacrylated gelatin (GelMA) was reacted with dopamine to form catechol-modified GeLMA (GelMA-C). The GelMA-C was nanocoated onto an iron-doped hydroxyapatite (FeHAp) nanorod via metal-catechol network coordination. The modified nanorod (FeHAp@GelMA-C) was loaded onto GelMA-based nanofibers. The nanorods loaded pre-fibers were electrospun onto GelMA solution and photochemically crosslinked to fabricate a fiber-reinforced hydrogel. The structural, mechanical, physicochemical, biocompatibility, swelling properties, osteogenic potential, and bone remodelling potential (using rat femoral defect model) of modified nanorods, simple hydrogel, and nanorod-loaded fiber-reinforced hydrogel were studied. The results supported that the interface interaction between GelMA-C/nanorods, nanorods/nanofibers, nanorods/hydrogels, and nanofiber/hydrogels significantly improved the microstructural and mechanical properties of the scaffold. Compared to pristine hydrogel, the nanorod-loaded fiber-reinforced scaffold better supported cellular responses, osteogenic differentiation, matrix mineralization, and accelerated bone regeneration. The nanorod-loaded fiber-reinforced hydrogel proved more biomimetic and cell-instructive for guided bone reconstruction.

Poly (Lactic Acid) Applications in Biomedical Engineering

Medical devices like implants are playing a pivotal role in medicine. As a polyester, Polylactic acid (PLA) and its copolymers are widely used in the medical area. They are used in several sections including cardiovascular and orthopedic devices, as well as advanced technologies of tissue engineering and drug delivery. In this paper, cardiovascular devices including applications of PLLA coating as drug delivery system and BVS material are introduced. Specifically, PLA can be used to foster scaffolds for bone tissue and cardiovascular tissue engineering. Then this paper introduces PLA applied in the form of nanoparticles and micelles in drug delivery. The special degrading process makes PLA an active drug delivery carrier. And it could also be used to produce biodegradable orthopaedic operation devices and offer the advantage of being free from taking out of the human body. Processing techniques are pivotal prerequisites of applications of medical usage, like electrospun fibers are used in cardiovascular and drug delivery applications. The paper summarizes the use of PLA material in those areas, and foresees the future for a prediction of the attractive prospect. Although the applications are faced with limitations like mechanical properties now, they still have a promising future in biomedicine.

Vancomycin-loaded methylcellulose aerogel scaffolds for advanced bone tissue engineering

Scaffolds grafting combined with local delivery of antibiotics at the injury site may promote bone regeneration along with prevention of infections. In this work, a processing strategy combining the 3D-printing of polysaccharide-based inks with supercritical (sc)CO2 technology was employed to manufacture drug-loaded, nanostructured, and personalized-to-patient aerogels for the first time. Methylcellulose (MC) was employed as graft matrix endowed with nanohydroxyapatite (nHA) to confer bioactivity as required in bone tissue engineering (BTE). MC-nHA aerogels were obtained through the 3D-printing of hydrogel-based scaffolds followed by scCO2 drying. Aerogels were loaded with vancomycin (VAN), an antibiotic employed in the management of bone infections. Textural properties and printing fidelity of scaffolds were studied as well as VAN release, long-term bioactivity, and pre-osteoblasts mineralization. In vitro cell studies and in vivo Artemia salina tests were carried out to evaluate the potential toxicity of the antibiotic-loaded aerogels. Aerogels efficacy in inhibiting bacterial growth was assessed by antimicrobial tests with Staphylococcus aureus. Textural stability of the aerogels after 7 months of storage was also evaluated. Obtained results showed that the scaffolds promoted the intended two-in-one effect (bone repair and infection management simultaneously) in a personalized way, regulating formulation design, drug dose, and porosity.

Synthesis of scale-like nano-hydroxyapatite and preparation of biodegradable woven scaffolds for bone tissue engineering

Bone tissue engineering scaffolds should have bone compatibility, biological activity, porosity, and degradability. In this study, flake-like hydroxyapatite was synthesized by hydrothermal method and mixed with sodium alginate to make a gel, which was injected into a hollow braid. Porous and degradable SA/n-Hap woven scaffolds were prepared by freeze-drying technology. The morphology of hydroxyapatite was characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and x-ray diffraction. The scaffolds were characterized by an improved liquid replacement method, compression test, and degradation test. The results showed that the hydroxyapatite synthesized at 160 °C had a scaly morphology. The prepared scaffold had a pore size of 5–100 μm, a porosity of 60%−70%, and a swelling rate of more than 300%. After 21 d the degradation rate reached 5.54%, and a cell survival rate of 214.98%. In summary, it is feasible to prepare porous bone scaffolds for potential bone tissue engineering. This study shows the feasibility of applying textile structures to the field of tissue scaffolds and provides a new idea for the application structure of tissue engineering scaffolds.

Natural bone inspired core–shell triple-layered gel/PCL/gel 3D printed scaffolds for bone tissue engineering

Despite technological advancements in bone tissue engineering, it is still a challenge to fabricate a scaffold with high bioactivity as well as high mechanical strength that can promote osteogenesis as well as bear load. Here we developed a 3D printed gel-polymer multi-layered hybrid scaffold. The innermost layer is porous gel-based framework made of gelatin/carboxymethyl-chitin/nano-hydroxyapatite and is cryogenically 3D printed. Further, the second and middle layer of micro-engineered polycaprolactone (PCL) is infused in the gel with controlled penetration and tuneable coating thickness. The PCL surface is further coated with a third and final thin layer of gel matrix used for the first layer. This triple-layered structure demonstrates compression strength and modulus of 13.07 ± 1.15 MPa and 21.8 ± 0.82 MPa, respectively, post 8 weeks degradation which is >3000% and >700% than gel scaffold. It also shows degradation of 6.84 ± 0.70% (83% reduction than gel scaffold) after 12 weeks and swelling of 69.09 ± 6.83% (81% reduction) as compared to gel scaffolds. Further, nearly 300%, 250%, 50%, and 440% increase in cellular attachment, proliferation, protein generation, and mineralization, respectively are achieved as compared to only PCL scaffolds. Thus, these hybrid scaffolds offer high mechanical strength, slow degradation rate, high bioactivity, and high osteoconductivity. These multifunctional scaffolds have potential for reconstructing non-load-bearing bone defects like sinus lift, jaw cysts, and moderate load-bearing like reconstructing hard palate, orbital palate, and other craniomaxillofacial bone defects.