Scaffolds For Bone Regeneration Research Articles

Neodymium (III)-containing poly(lactide-co-glycolide)-coated robocast bioactive glass scaffolds for photothermal therapy and bone regeneration

In this study, trivalent neodymium-doped silicate-based 13–93 bioactive glass scaffolds were prepared by the robocasting method using sol-gel-derived bioactive glass powders for tissue engineering applications. Sintered scaffolds were coated by borate-based 13-93B3 bioactive glass-containing polylactide-co-glycolide solution. The produced composite scaffolds’ mechanical, morphological, and structural characteristics were thoroughly examined, as their in vitro bioactivity in cell culture media and simulated body fluid. Furthermore, the scaffolds’ amoxicillin adsorption and release behavior was examined over time. The outcomes demonstrated that it was feasible to effectively create periodic, mesh-like-patterned robocast glass scaffolds utilizing Nd3+-doped sol-gel-derived bioactive glass powders. The scaffolds’ compressive strengths ranged from 10.02 MPa to 18.6 MPa, with the PLGA-coated scaffolds exhibiting the highest strength values. All of the scaffolds that were submerged in simulated body fluid for 28 days showed hydroxyapatite formation. The presence of borate glass on the surface of the silicate-based glass scaffolds improved the hydroxyapatite formation ability. The quantity of drug adsorption for all types of scaffolds was measured to be between 4 and 9% whereas the cumulative drug release was in the range of 58 to 96%. Borate glass particle-containing PLGA coating enhanced the drug delivery behavior.

Development and Evaluation of Alginate- and Carrageenan-Incorporated Scaffold for Bone Regeneration: An In Vitro Study

Development and Evaluation of Alginate- and Carrageenan-Incorporated Scaffold for Bone Regeneration: An In Vitro Study

Bioinspired poly-dopamine/nano-hydroxyapatite: an upgrading biocompatible coat for 3D-printed polylactic acid scaffold for bone regeneration.

Poly-lactic acid (PLA) has been proposed in dentistry for several regenerative procedures owing to its biocompatibility and biodegradability. However, the presence of methyl groups renders PLA hydrophobic, making the surface less ideal for cell attachment, and it does not promote tissue regeneration. Upgrading PLA with inductive biomaterial is a crucial step to increase the bioactivity of the PLA and allow cellular adhesion. Our purpose is to evaluate biocompatibility, bioactivity, cellular adhesion, and mechanical properties of 3D-printed PLA scaffold coated with poly-dopamine (PDA) and nano-hydroxyapatite (n-HA) versus PLA and PLA/n-HA scaffolds. The fused deposition modelling technique was used to print PLA, PLA with embedded n-HA particles, and PLA scaffold coated with PDA/n-HA by immersion. After matrices characterization for their chemical composition and surface properties, testing the compressive strength was pursued using a universal testing machine. The bioactivity of scaffolds was evaluated by monitoring the formation of calcium phosphate compounds after simulated body fluid immersion. The PLA/PDA/n-HA scaffold showed the highest compressive strength which was 29.11 ± 7.58 MPa with enhancing calcium phosphate crystals deposition with a specific calcium polyphosphate phase formed exclusively on PLA/PDA/n-HA. With cell viability assay, the PDA/n-HA-coated matrix was biocompatible with increase in the IC50, reaching ⁓176.8 at 72 without cytotoxic effect on the mesenchymal stem cells, promoting their adhesion and proliferation evaluated by confocal microscopy. The study explored the biocompatibility, bioactivity, and the cell adhesion ability of PDA/n-HA coat on a 3D-printed PLA scaffold that qualifies its use as a promising regenerative material.

Core-shell 3D printed biodegradable calcium phosphate cement—Alginate scaffolds for possible bone regeneration applications

The core/shell 3D printing process using CPC and alginate is intended to create biodegradable scaffolds that have a similar stability to bone tissue and also offer sufficient and continuous antibiotic release. In this way, a patient-specific and patient-friendly process will be established, which should optimally support the human organism in its regeneration. To generate the best possible strength values, the printed scaffolds underwent various post-treatments and were then tested in a material test. The test methods included self-setting, storage in a drying cabinet with a water-saturated atmosphere at 37°C, followed by incubation in PBS, freeze-drying, and coating the samples with alginate. Additionally, a degradation test at pH 7.4 and pH 5 was carried out to test stability under in vitro conditions. It was shown that the untreated and freeze-dried samples failed at a maximum load of 30–700 N, while the remaining scaffolds could withstand a load of at least 2,000 N. At this failure load, most of the test series showed an average deformation of 43.95%. All samples, therefore, remained below the strength of cancellous bone. However, based on a 20% load after surgery, the coated scaffolds represented the best possible alternative, with a Young’s modulus of around 1.71 MPa. We were able to demonstrate that self-setting occurs in core-shell printed CPC/alginate scaffolds after only 1 day, and that mass production is possible. By coating with alginate, the compressive strength could be increased without the need for additional post-treatment. The mechanical strength was sufficient to be available as a scaffold for bone regeneration and additionally as a drug delivery device for future applications and experiments.

A Multidisciplinary Evaluation of Three-Dimensional Polycaprolactone Bioactive Glass Scaffolds for Bone Tissue Engineering Purposes.

In the development of bone graft substitutes, a fundamental step is the use of scaffolds with adequate composition and architecture capable of providing support in regenerative processes both on the tissue scale, where adequate resistance to mechanical stress is required, as well as at the cellular level where compliant chemical-physical and mechanical properties can promote cellular activity. In this study, based on a previous optimization study of this group, the potential of a three-dimensional construct based on polycaprolactone (PCL) and a novel biocompatible Mg- and Sr-containing glass named BGMS10 was explored. Fourier-transform infrared spectroscopy and scanning electron microscopy showed the inclusion of BGMS10 in the scaffold structure. Mesenchymal stem cells cultured on both PCL and PCL-BGMS10 showed similar tendencies in terms of osteogenic differentiation; however, no significant differences were found between the two scaffold types. This circumstance can be explained via X-ray microtomography and atomic force microscopy analyses, which correlated the spatial distribution of the BGMS10 within the bulk with the elastic properties and topography at the cell scale. In conclusion, our study highlights the importance of multidisciplinary approaches to understand the relationship between design parameters, material properties, and cellular response in polymer composites, which is crucial for the development and design of scaffolds for bone regeneration.

Design, In Vitro Evaluation and In Vivo Biocompatibility of Additive Manufacturing Three-Dimensional Printing of β beta-Tricalcium Phosphate Scaffolds for Bone Regeneration

The reconstruction of bone deficiencies remains a challenge due to the limitations of autologous bone grafting. The objective of this study is to evaluate the bone regeneration efficacy of additive manufacturing of tricalcium phosphate (TCP) implants using lithography-based ceramic manufacturing (LCM). LCM uses LithaBone TCP 300 slurry for 3D printing, producing cylindrical scaffolds. Four models of internal scaffold geometry were developed and compared. The in vitro studies included cell culture, differentiation, seeding, morphological studies and detection of early osteogenesis. The in vivo studies involved 42 Wistar rats divided into four groups (control, membrane, scaffold (TCP) and membrane with TCP). In each animal, unilateral right mandibular defects with a total thickness of 5 mm were surgically performed. The animals were sacrificed 3 and 6 months after surgery. Bone neoformation was evaluated by conventional histology, radiology, and micro-CT. Model A (spheres with intersecting and aligned arrays) showed higher penetration and interconnection. Histological and radiological analysis by micro-CT revealed increased bone formation in the grafted groups, especially when combined with a membrane. Our innovative 3D printing technology, combined with precise scaffold design and efficient cleaning, shows potential for bone regeneration. However, further refinement of the technique and long-term clinical studies are crucial to establish the safety and efficacy of these advanced 3D printed scaffolds in human patients.

Silver and silicon doped βTCP scaffolds with gentamicin or ceftazidime loaded P(3HB) coatings as multifunctional biomaterials for bone regeneration

The risk of bacterial infections is a significant challenge faced frequently in the use of implants or scaffolds for bone regeneration. Therefore, this study focusses on the development and characterisation of novel β tricalcium phosphate (βTCP) scaffolds co-doped with silver and silicon, along with composites coated with antibiotic-loaded poly(3-hydroxybutyrate) (P(3HB)) layers. The successful incorporation of silver and silicon dopants while maintaining the formation of βTCP phase was confirmed using X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) analysis. The developed materials demonstrated comparable total and open porosity (∼64–70 vol%), suggesting high interconnectivity between pores conducive to nutrient transport and tissue repair. The increase in compressive strength was achieved for both doped (4.73 ± 0.79 MPa) and P(3HB) coated (5.79 ± 0.92 MPa) scaffolds due to the fine bioceramic microstructure and polymeric coating. Silver and silicon-modified βTCP demonstrated enhanced growth inhibition of Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial strains in vitro compared to the pure βTCP. P(3HB) coatings, enriched with gentamicin or ceftazidime, exhibited burst and sustained release of the antibiotics from the scaffolds up to 120 h further intensifying the bacteria-killing capability, with evident inhibition zones observed in vitro. Moreover, the composites exhibited apatite-forming ability, suggesting their bioactive potential. In vivo evaluation using Caenorhabditis elegans demonstrated the lack of toxicity of the tested materials. The simultaneous incorporation of the dopants and antibiotic-loaded P(3HB) coatings not only offer a dual antibacterial approach but may also facilitate bone regeneration. However, further in vitro and in vivo investigations are needed to assess their potential in clinical application.

Engineering biomimetic scaffolds for bone regeneration: Chitosan/alginate/polyvinyl alcohol-based double-network hydrogels with carbon nanomaterials

In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively.

Molecularly Imprinted Macroporous Hydrogel Promotes Bone Regeneration via Osteogenic Induction and Osteoclastic Inhibition.

Macroporous hydrogels offer physical supportive spaces and bio-instructive environment for the seeded cells, where cell-scaffold interactions directly influence cell fates and subsequently affect tissue regeneration post-implantation. Effectively modifying bioactive motifs at the inner pore surface provides appropriate niches for cell-scaffold interactions. A molecular imprinting method and sacrificial templates are introduced to prepare inner pore surface modification in the macroporous hydrogels. In detail, acrylated bisphosphonates (Ac-BPs) chelating to templates (CaCO3 particles) are anchored on the inner pore surface of the methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA)-poly (ethylene glycol) diacrylate (PEGDA) macroporous hydrogel (GHP) to form a functional hydrogel scaffold (GHP-int-BP). GHP-int-BP, but not GHP, effectively crafts artificial cell niches to substantially alter cell fates, including osteogenic induction and osteoclastic inhibition, and promote in situ bone regeneration. These findings highlight that molecular imprinting on the inner pore surface in the hydrogel efficiently creates orthogonally additive bio-instructive scaffolds for bone regeneration.

Comparing the bone regeneration potential between a trabecular bone and a porous scaffold through osteoblast migration and differentiation: A multiscale approach.

Both cell migration and osteogenic differentiation are critical for successful bone regeneration. Therefore, understanding the mechanobiological aspects that govern these two processes is essential in designing effective scaffolds that promote faster bone regeneration. Studying these two factors at different locations is necessary to manage bone regeneration in various sections of a scaffold. Hence, a multiscale computational model was used to observe the mechanical responses of osteoblasts placed in different positions of the trabecular bone and gyroid scaffold. Fluid shear stresses in scaffolds at cell seeded locations (representing osteogenic differentiation) and strain energy densities in cells at cell substrate interface (representing cell migration) were observed as mechanical response parameters in this study. Comparison of these responses, as two critical factors for bone regeneration, between the trabecular bone and gyroid scaffold at different locations, is the overall goal of the study. This study reveals that the gyroid scaffold exhibits higher osteogenic differentiation and cell migration potential compared to the trabecular bone. However, the responses in the gyroid only mimic the trabecular bone in two out of nine positions. These findings can guide us in predicting the ideal cell seeded sites within a scaffold for better bone regeneration and in replicating a replaced bone condition by altering the physical parameters of a scaffold.

Preparation and Characterization of Chitosan/Hydroxyapatite Nanowire Composite Scaffolds for Bone Regeneration

Preparation and Characterization of Chitosan/Hydroxyapatite Nanowire Composite Scaffolds for Bone Regeneration

Synthesis and characterization of nano-biocomposite (PMMA-hydroxyapatite - CaZrO3) for bone tissue engineering

ABSTRACT In a common scenario, bone fractures have a self-healing function with free-surgical intervention. However, some fractures in bone tissue are complex and leave behind remnant deformation that requires biomaterials for replacement. The aim of this study is to develop a new composite 3D scaffold for bone regeneration and replacement composed of calcium zirconate (CaZrO3), hydroxyapatite (HA) and polymethylmethacrylate (PMMA) polymer. Different 3D scaffolds were fabricated by mixing 90, 80, 70, and 60 wt. % PMMA with HA and CaZrO3 nanoparticles in different concentrations. X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) techniques were applied to characterize the 3D composite scaffold properties. Furthermore, the mechanical properties of the fabricated scaffolds were investigated using Brazilian diametral fracture test. It was found that incorporating a uniform distribution of HA nanoparticles significantly increased the surface roughness of the composite scaffold. Furthermore, the fracture strength of the fabricated 3D scaffolds showed a remarkable improvement of 86% in the sample containing 90% PMMA, 7% HA, and 3% CaZrO3 compared to the sample devoid of CaZrO3. Our findings strongly indicate that integrating hybrid CaZrO3-HA nanoparticles into PMMA polymer for the production of 3D composite scaffolds holds significant promise for bone tissue applications, potentially enhancing their efficacy and performance.

Advancements in Photothermal Therapy Using Near-Infrared Light for Bone Tumors.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

Architecture of β-lactoglobulin coating modulates bioinspired alginate dialdehyde-gelatine/polydopamine scaffolds for subchondral bone regeneration

In this study, we developed polydopamine (PDA)-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds for subchondral bone regeneration. These polymeric scaffolds were then coated with β-Lactoglobulin (β-LG) at concentrations of 1 mg/ml and 2 mg/ml. Morphological analysis indicated a homogeneous coating of the β-LG layer on the surface of network-like scaffolds. The β-LG-coated scaffolds exhibited improved swelling capacity as a function of the β-LG concentration. Compared to ADA-GEL/PDA scaffolds, the β-LG-coated scaffolds demonstrated delayed degradation and enhanced biomineralization. Here, a lower concentration of β-LG showed long-lasting stability and superior biomimetic hydroxyapatite mineralization. According to the theoretical findings, the single-state, representing the low concentration of β-LG, exhibited a homogeneous distribution on the surface of the PDA, while the dimer-state (high concentration) displayed a high likelihood of uncontrolled interactions. β-LG-coated ADA-GEL/PDA scaffolds with a lower concentration of β-LG provided a biocompatible substrate that supported adhesion, proliferation, and alkaline phosphatase (ALP) secretion of sheep bone marrow mesenchymal stem cells, as well as increased expression of osteopontin (SPP1) and collagen type 1 (COL1A1) in human osteoblasts. These findings indicate the potential of protein-coated scaffolds for subchondral bone tissue regeneration. Statement of SignificanceThis study addresses a crucial aspect of osteochondral defect repair, emphasizing the pivotal role of subchondral bone regeneration. The development of polydopamine-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds, coated with β-Lactoglobulin (β-LG), represents a novel approach to potentially enhance subchondral bone repair. β-LG, a milk protein rich in essential amino acids and bioactive peptides, is investigated for its potential to promote subchondral bone regeneration. This research explores computationally and experimentally the influence of protein concentration on the ordered or irregular deposition, unravelling the interplay between coating structure, scaffold properties, and in-vitro performance. This work contributes to advancing ordered protein coating strategies for subchondral bone regeneration, providing a biocompatible solution with potential implications for supporting subsequent cartilage repair.

Constructing osteo-inductive bio-ink for 3D printing through hybridization of gelatin with maleic acid modified bacterial cellulose by regulating addition volumes of maleic acid solution

Bacterial cellulose (BC) is an exopolysaccharide with unique properties that has been applied in various fields. However, the dense and intertwined nature of BC fibers limits its use in certain applications, including 3D printing scaffolds for bone regeneration. In this work, a controllable BC-based bio-ink for 3D printing was successfully prepared by modifying the neat BC through maleic acid (MA) treatment, aiming to promote bone tissue regeneration. To achieve homogeneous BC dispersions while preserving its crystalline and chemical properties, BC was modified by MA solution (60 %, w/V) with solid-liquid ratio from 1꞉5 to 1꞉50 (w/V) to obtain MA-BC dispersions. The analysis results from microstructure, chemical group, crystallinity, and wettability indicated that the BC/MA solution with ratio of 1꞉30 demonstrated the best pre-treatment performance to obtain MA-BC. Subsequently, by combining MA-BC with gelatin, we successfully formulated MA-BC-GEL gels with favorable rheological properties and compression modulus, which can be used as promising bio-inks for 3D bioprinting applications. In vitro tests demonstrated 1꞉30 MA-BC possessed excellent biocompatibility, a significant ability to express the alkaline phosphatase gene and osteogenic-related genes, and facilitated the formation of mineralized nodules. The utilization of this novel bio-ink in scaffold preparation for bone regeneration highlights the promising application of modified BC in bone tissue engineering field.

Aspirin-Loaded Anti-Inflammatory ZnO-SiO2 Aerogel Scaffolds for Bone Regeneration.

The increasing aging of the population has elevated bone defects to a significant threat to human life and health. Aerogel, a biomimetic material similar to an extracellular matrix (ECM), is considered an effective material for the treatment of bone defects. However, most aerogel scaffolds suffer from immune rejection and poor anti-inflammatory properties and are not well suited for human bone growth. In this study, we used electrospinning to prepare flexible ZnO-SiO2 nanofibers with different zinc concentrations and further assembled them into three-dimensional composite aerogel scaffolds. The prepared scaffolds exhibited an ordered pore structure, and chitosan (CS) was utilized as a cross-linking agent with aspirin (ASA). Interestingly, the 1%ZnO-SiO2/CS@ASA scaffolds not only exhibited good biocompatibility, bioactivity, anti-inflammation, and better mechanical properties but also significantly promoted vascularization and osteoblast differentiation in vitro. In the mouse cranial defect model, the BV/TV data showed a higher osteogenesis rate in the 1%ZnO-SiO2/CS group (10.94 ± 0.68%) and the 1%ZnO-SiO2/CS@ASA group (22.76 ± 1.83%), compared with the control group (5.59 ± 2.08%), and in vivo studies confirmed the ability of 1%ZnO-SiO2/CS@ASA to promote in situ regeneration of new bone. This may be attributed to the fact that Si4+, Zn2+, and ASA released from 1%ZnO-SiO2/CS@ASA scaffolds can promote angiogenesis and bone formation by stimulating the interaction between endothelial cells (ECs) and BMSCs, as well as inducing macrophage differentiation to the M2 type and downregulating the expression of pro-inflammatory factor (TNF-α) to modulate local inflammatory response. These exciting results and evidence suggest that it provides a new and effective strategy for the treatment of bone defects.

Development and characterization of ceramic-polymeric hybrid scaffolds for bone regeneration: incorporating of bioactive glass BG-58S into PDLLA matrix

In recent years, there has been a notable surge of interest in hybrid materials within the biomedical field, particularly for applications in bone repair and regeneration. Ceramic-polymeric hybrid scaffolds have shown promising outcomes. This study aimed to synthesize bioactive glass (BG-58S) for integration into a bioresorbable polymeric matrix based on PDLLA, aiming to create a bioactive scaffold featuring stable pH levels. The synthesis involved a thermally induced phase separation process followed by lyophilization to ensure an appropriate porous structure. BG-58S characterization revealed vitreous, bioactive, and mesoporous structural properties. The scaffolds were analyzed for morphology, interconnectivity, chemical groups, porosity and pore size distribution, zeta potential, pH, in vitro degradation, as well as cell viability tests, total protein content and mineralization nodule production. The PDLLA scaffold displayed a homogeneous morphology with interconnected macropores, while the hybrid scaffold exhibited a heterogeneous morphology with smaller diameter pores due to BG-58S filling. The hybrid scaffold also demonstrated a pH buffering effect on the polymer surface. In addition to structural characteristics, degradation tests indicated that by incorporating BG-58S modified the acidic degradation of the polymer, allowing for increased total protein production and the formation of mineralization nodules, indicating a positive influence on cell culture.

Piezoelectric core-shell fibrous scaffolds of PVDF-ZnO/PCL for bone regeneration

One promising approach to improve bone regeneration is the use of piezoelectric scaffolds, which can positively affect cell growth and proliferation. PVDF, as a piezoelectric polymer, is an attractive candidate for use as a bone scaffold. However, other components should be added to PVDF to improve wettability, biodegradability, biocompatibility, and other biological properties. In this research, PVDF containing ZnO-PCL core-shell fiber composites were fabricated by coaxial electrospinning. TEM images were used to determine the proper electrospinning parameters that can provide a homogenous core/shell structure. Afterward, the surface of the samples was corona-treated to improve wettability. FTIR spectroscopy was used to estimate the piezoelectric β phase fraction in the core PVDF fibers, which demonstrated that the highest β phase fraction was obtained in the presence of 0.5 wt% ZnO nanoparticles. The tensile test results revealed that by adding ZnO nanoparticles to the scaffolds, the ultimate tensile strength of samples decreased, yet the values were in the acceptable range. The water contact angle measurements showed that the corona treatment could successfully reduce the contact angle from about 130° to 60°. Based on the obtained results, the F-0.5Z sample was chosen as the optimum sample and was used for biological and piezoelectric assessments. It rendered the piezoelectric output of 6.5 pC/N. In vitro assessments showed that this sample is biodegradable and bioactive, could support cell attachment and proliferation and intensified calcium mineralization. The composite containing 0.5 wt% ZnO had the best result and could be used as a scaffold in bone regeneration and repair.

Fabrication and characterization of a bioactive composite scaffold based on polymeric collagen/gelatin/nano β-TCP for alveolar bone regeneration

One strategy to correct alveolar bone defects is use of bioactive bone substitutes to maintain the structure of defect site and facilitate cells and vessels' ingrowth. This study aimed to fabricate and characterize the freeze-dried bone regeneration scaffolds composed of polymeric Type I collagen, nano Beta-tricalcium phosphate (β-TCP), and gelatin. The stable structures of scaffolds were obtained by thermal crosslinking and EDC/NHS ((1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/(N-hydroxysuccinimide)) chemical crosslinking processes. Subsequently, the physicochemical and biological properties of the scaffolds were characterized and assessed. The results indicated the bioactive composite scaffolds containing 10% and 20% (w/v) nano β-TCP exhibited suitable porosity (84.45 ± 25.43 nm, and 94.51 ± 14.69 nm respectively), a rapid swelling property (reaching the maximum swelling rate at 1 h), excellent degradation resistance (residual mass percentage of scaffolds higher than 80% on day 90 in PBS and Type I collagenase solution respectively), and sustained calcium release capabilities. Moreover, they displayed outstanding biological properties, including superior cell viability, cell adhesion, and cell proliferation. Additionally, the scaffolds containing 10% and 20% (w/v) nano β-TCP could promote the osteogenic differentiation of MC3T3-E1. Therefore, the bioactive composite scaffolds containing 10% and 20% (w/v) nano β-TCP could be further studied for being used to treat alveolar bone defects in vivo.

Three-Dimensional Printing of Drug-Eluting Implantable PLGA Scaffolds for Bone Regeneration.

Despite rapid progress in tissue engineering, the repair and regeneration of bone defects remains challenging, especially for non-homogenous and complicated defects. We have developed and characterized biodegradable drug-eluting scaffolds for bone regeneration utilizing direct powder extrusion-based three-dimensional (3D) printing techniques. The PLGA scaffolds were fabricated using poly (lactic-co-glycolic acid) (PLGA) with inherent viscosities of 0.2 dl/g and 0.4 dl/g and ketoprofen. The effect of parameters such as the infill, geometry, and wall thickness of the drug carrier on the release kinetics of ketoprofen was studied. The release studies revealed that infill density significantly impacts the release performance, where 10% infill showed faster and almost complete release of the drug, whereas 50% infill demonstrated a sustained release. The Korsmeyer-Peppas model showed the best fit for release data irrespective of the PLGA molecular weight and infill density. It was demonstrated that printing parameters such as infill density, scaffold wall thickness, and geometry played an important role in controlling the release and, therefore, in designing customized drug-eluting scaffolds for bone regeneration.