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Degradable phosphate glasses have shown favorable properties for tissue engineering. By changing the composition of the glasses, the degradation rate, and ion release are controllable. Zinc oxide can function as a glass network modifier and has been shown to play a positive role in bone formation. Also, phosphate glasses can easily be processed into microspheres, which can be used as microcarriers. This study aims to develop zinc phosphate glasses microspheres and explore the optimized size and composition for applications in bone tissue engineering. Zinc-titanium-calcium-sodium phosphate glasses with 0, 1, 3, 5, or 10 mol % zinc oxide were prepared and processed into microspheres. The smaller microspheres ranged in size from 50 to 106 µm, while the larger ones ranged from 106 to 150 µm. The characteristics of glasses were examined. The osteoblastic cell line MC3T3-E1 was cultured on the surface of microspheres and the cell viability was examined. To evaluate osteogenic differentiation, Alizarin Red S staining, quantitative reverse transcription polymerase chain reaction, and western blot analysis were performed after 14 days. Different sizes of zinc phosphate glass microspheres were successfully made. The glass microspheres with <10 mol % zinc oxide were able to support the adhesion and proliferation of MC3T3-E1 cell lines. The relative gene expression of BMP2 was significantly upregulated in the smaller glass microspheres containing 3 mol % zinc oxide (26-fold, p < .001) and both sizes of microspheres containing 5 mol % zinc oxide (smaller: 27-fold, p < .001; larger: 35-fold, p < .001). Additionally, cluster formation was observed in glass microspheres after 14 days, and the mineralization of MC3T3-E1 cell lines was promoted. Based on these findings, the glass microspheres containing 3-5 mol % of zinc oxide can promote osteogenic differentiation for MC3T3-E1 cells.
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The application of bone grafting materials in bone tissue engineering is paramount for treating severe bone defects. In this comprehensive review, we explore the significance and novelty of utilizing bioactive polymers as grafts for successful bone repair. Unlike metals and ceramics, polymers offer inherent biodegradability and biocompatibility, mimicking the native extracellular matrix of bone. While these polymeric micro-nano materials may face challenges such as mechanical strength, various fabrication techniques are available to overcome these shortcomings. Our study not only investigates diverse biopolymeric materials but also illuminates innovative fabrication methods, highlighting their importance in advancing bone tissue engineering.
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Despite advancements in therapeutic techniques, restoring bone tissue after damage remains a challenging task. Tissue engineering or targeted drug delivery solutions aim to meet the pressing clinical demand for treatment alternatives by creating substitute materials that imitate the structural and biological characteristics of healthy tissue. Polymers derived from natural sources typically exhibit enhanced biological compatibility and bioactivity when compared to manufactured polymers. Chitosan is a unique polysaccharide derived from chitin through deacetylation, offering biodegradability, biocompatibility, and antibacterial activity. Its cationic charge sets it apart from other polymers, making it a valuable resource for various applications. Modifications such as thiolation, alkylation, acetylation, or hydrophilic group incorporation can enhance chitosan's swelling behavior, cross-linking, adhesion, permeation, controllable drug release, enzyme inhibition, and antioxidative properties. Chitosan scaffolds possess considerable potential for utilization in several biological applications. An intriguing application is its use in the areas of drug distribution and bone tissue engineering. Due to their excellent biocompatibility and lack of toxicity, they are an optimal material for this particular usage. This article provides a comprehensive analysis of osteoporosis, including its pathophysiology, current treatment options, the utilization of natural polymers in disease management, and the potential use of chitosan scaffolds for drug delivery systems aimed at treating the condition.
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Quitosana , Osteoporose , Alicerces Teciduais , Quitosana/química , Humanos , Osteoporose/tratamento farmacológico , Alicerces Teciduais/química , Engenharia Tecidual , Animais , Sistemas de Liberação de Medicamentos , Materiais Biocompatíveis/químicaRESUMO
In osteoporosis, bone quality adversely affects the tissue structural competence which increases the risk of a complicated fracture healing. In the present study highly potent scaffold containing natural coral particles was designed and considered for the healing of critical size bone defect in osteoporosis rat model. Scaffold morphological evaluation confirmed the porous nanofibrous structure. Water uptake of about 900 % was obtained for the fabricated scaffold as the result of its composition and three-dimensional structure. Mechanical analysis revealed the compressive modulus of about 50 kPa for the fabricated coral-incorporated nanofibrous structure. In vitro cellular assessments revealed that the designed scaffold induces no toxicity and provides the proper substrate for cell attachment together with increased and prolonged cell proliferation. In vivo experiments demonstrated that implantation of the fabricated scaffold in the femoral defects of osteoporotic rats significantly increased the number of osteocytes and osteoblasts, and enhanced the BTV, and BMP-2 expression compared with the control group. Furthermore, it was observed that seeding the scaffolds with MSCs prior to implantation, resulted in substantial improvements in mRNA expression of the BMP-2 and VEGF genes and considerable enhancement in stereological findings such as significantly higher number of osteoblasts, osteocytes, TVB, and BTV.
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Commercially available bioactive glasses (BAGs) are exclusively used in powder form, due to their tendency to crystallize. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. This study investigates the potential of 1393B20 scaffolds to support bone regeneration and mineralization in vitro and in vivo, in comparison to silicate 1393. Both scaffolds supported human adipose stem cells proliferation, either in direct contact for the 1393, or mainly around for the 1393B20. Similarly, both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. In addition, these scaffolds supported bone regeneration and osteoclast/osteoblast activity in vivo in critical-sized rat calvarial defect. Nevertheless, mineralization and collagen formation were significantly enhanced for the 1393B20, at 3-months post-implantation, assigned to faster and more complete dissolution of the scaffolds. Thus, 1393B20 demonstrates greater promise for bone tissue engineering certainly due to its time-controlled release of boron and silicon. STATEMENT OF SIGNIFICANCE: Bioactive glasses (BAGs) show great promise in bone tissue engineering as they effectively bond with bone tissue, fostering integration and regeneration. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. Both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. The presence of boron in the 1393B20 enhanced mineralization and collagen formation in vivo compared to 1393, probably due to its faster dissolution rate. Here, 1393B20 demonstrated greater promise for bone tissue engineering compared to the well-known 1393 BAG.
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Bone tissue engineering offers a promising alternative to stimulate the regeneration of damaged tissue, overcoming the limitations of conventional autografts and allografts. Recently, titanium alloy (Ti) implants have garnered significant attention for treating critical-sized bone defects, especially with the advancement of 3D printing technology. Although Ti alloys have impressive versatility, their lack of cellular adhesion, osteogenic and antibacterial properties are significant factors that contribute to their failure. Hence, to overcome these obstacles, this study aimed to incorporate osteoinductive and antibacterial cue-loaded hydrogels into 3D-printed Ti (3D-Ti) scaffolds. 3D-Ti scaffolds were synthesized using the direct metal laser sintering method and loaded with a gelatin (Gel) hydrogel containing strontium-doped silver nanoparticles (Sr-Ag NPs). Compared with Ag NPs, Sr-doped Ag NPs increased the expression of Runx2 mRNA, which is a key bone transcription factor. We subjected the bioactive 3D-hybrid scaffolds (3D-Ti/Gel/Sr-Ag NPs) to physicochemical and material characterization, followed by cytocompatibility and osteogenic evaluation. The microporous and macroporous topographies of the scaffolds with Sr-Ag NPs showed increased Runx2 expression and matrix mineralization, with potent antibacterial properties. Therefore, the 3D-Ti scaffolds incorporated with Sr-Ag NP-loaded Gel hydrogels favored osteoblast differentiation and antibacterial activity, indicating their potential for orthopedic applications.
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Antibacterianos , Diferenciação Celular , Gelatina , Hidrogéis , Nanopartículas Metálicas , Osteoblastos , Osteogênese , Impressão Tridimensional , Prata , Estrôncio , Engenharia Tecidual , Alicerces Teciduais , Titânio , Prata/química , Prata/farmacologia , Gelatina/química , Estrôncio/química , Estrôncio/farmacologia , Titânio/química , Titânio/farmacologia , Engenharia Tecidual/métodos , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Antibacterianos/química , Antibacterianos/farmacologia , Alicerces Teciduais/química , Hidrogéis/química , Hidrogéis/farmacologia , Nanopartículas Metálicas/química , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Camundongos , Osso e Ossos/efeitos dos fármacosRESUMO
The design of three-dimensional (3D) scaffolds should focus on creating highly porous, 3D structures with an interconnected pore network that supports cell growth. The scaffold's pore interconnectivity is directly linked to vascularization, cell seeding, guided cell migration, and transportation of nutrients and metabolic waste. In this study, different types of food flavors including monosodium glutamate, sugar, and sodium chloride were used as the porogens along with PCL/PVP blend polymer for solvent casting/particulate leaching method. The morphology, porosity, interconnectivity, chemical composition, water absorption, and mechanical properties of the fabricated scaffolds are carefully characterized. The scaffolds are biocompatible in bothin vitroandin vivoexperiments and do not trigger any inflammatory response while enhancing new bone formation and vascularization in rabbit calvaria critical-sized defects. The new bone merges and becomes denser along with the experiment timeline. The results indicate that the 3D PCL/PVP scaffolds, using monosodium glutamate as porogen, exhibited suitable biological performance and held promise for bone tissue engineering in oral and maxillofacial surgery.
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Materiais Biocompatíveis , Glutamato de Sódio , Solventes , Engenharia Tecidual , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Coelhos , Engenharia Tecidual/métodos , Porosidade , Solventes/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Poliésteres/química , Teste de Materiais , Crânio/efeitos dos fármacos , Polivinil/química , Regeneração Óssea/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Osso e Ossos/metabolismoRESUMO
The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo, and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n = 75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area = 15.02), contrasting with the partial integration (% non-integrated bone area = 56.10; p < 0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10 ± 1.75) exhibited hardness similar to native bone (31.07 ± 2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. STATEMENT OF SIGNIFICANCE.
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Introduction: Bone tissue engineering seeks innovative materials that support cell growth and regeneration. Electrospun nanofibers, with their high surface area and tunable properties, serve as promising scaffolds. This study explores the incorporation of flaxseed extract, rich in polyphenolic compounds, into polyvinyl alcohol (PVA) nanofibers to improve their application in bone tissue engineering. Methods: High-performance liquid chromatography (HPLC) identified ten key compounds in flaxseed extract, including polyphenolic acids and flavonoids. PVA nanofibers were fabricated with 30 wt.% flaxseed extract (P70/E30) via electrospinning. We optimized characteristics like diameter, hydrophilicity, swelling behavior, and hydrolytic degradation. MG-63 osteoblast cultures were used to assess scaffold efficacy through cell adhesion, proliferation, viability (MTT assay), and differentiation. RT-qPCR measured expression of osteogenic genes RUNX2, COL1A1, and OCN. Results: Flaxseed extract increased nanofiber diameter from 252 nm (pure PVA) to 435 nm (P70/E30). P70/E30 nanofibers showed higher cell viability (102.6% vs. 74.5% for pure PVA), although adhesion decreased (151 vs. 206 cells/section). Notably, P70/E30 enhanced osteoblast differentiation, significantly upregulating RUNX2, COL1A1, and OCN genes. Discussion: Flaxseed extract incorporation into PVA nanofibers enhances bone tissue engineering by boosting osteoblast proliferation and differentiation, despite reduced adhesion. These properties suggest P70/E30's potential for regenerative medicine, emphasizing scaffold optimization for biomedical applications.
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In recent years, there has been a notable surge in the development of engineered bone scaffolds intended for the repair of bone defects. While autografts and allografts have traditionally served as the primary methods in bone tissue engineering, their inherent limitations have spurred the exploration of novel avenues in biomedical implant development. The emergence of bone scaffolds not only facilitates bone reconstruction but also offers a platform for the targeted delivery of therapeutic agents. There exists a pervasive interest in leveraging various drugs, proteins, growth factors, and biomolecules with osteogenic properties to augment bone formation, as the enduring side effects associated with current clinical modalities necessitate the pursuit of safer alternatives. Curcumin, the principal bioactive compound found in turmeric, has demonstrated notable efficacy in regulating the proliferation and differentiation of bone cells while promoting bone formation. Nevertheless, its utility is hindered by restricted water solubility and poor bioavailability. Strategies aimed at enhancing the solubility, stability, and bioavailability of curcumin, including formulation techniques such as liposomes and nanoparticles or its complexation with metals, have been explored. This investigation is dedicated to exploring the impact of curcumin on the proliferation, differentiation, and migration of osteocytes, osteoblasts, and osteoclasts.
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Background: In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration. Purpose of the Study: This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft. Methods: A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) system was analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs. Results and Conclusion: According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix.
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The compatibility of bone graft substitutes (BGS) with mesenchymal stem cells (MSCs) is an important parameter to consider for their use in repairing bone defects as it eventually affects the clinical outcome. In the present study, a few commercially available BGS - ß-tricalcium phosphate (ß-TCP), calcium sulfate, gelatin sponge, and different forms of hydroxyapatite (HAP) were screened for their interactions with MSCs from adipose tissue (ADSCs). It was demonstrated that HAP block favorably supported ADSC viability, morphology, migration, and differentiation compared to other scaffolds. The results strongly suggest the importance of preclinical evaluation of bone scaffolds for their cellular compatibility. Furthermore, the bone regenerative potential of HAP block with ADSCs was evaluated in an ex vivo bone defect model developed using patient derived trabecular bone explants. The explants were cultured for 45 days in vitro and bone formation was assessed by expression of osteogenic genes, ALP secretion, and high resolution computed tomography. Our findings confirmed active bone repair process in ex vivo settings. Addition of ADSCs significantly accelerated the repair process and improved bone microarchitecture. This ex vivo bone defect model can emerge as a viable alternative to animal experimentation and also as a potent tool to evaluate patient specific bone therapeutics under controlled conditions.
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Tecido Adiposo , Regeneração Óssea , Diferenciação Celular , Células-Tronco Mesenquimais , Engenharia Tecidual , Alicerces Teciduais , Humanos , Tecido Adiposo/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Células-Tronco Mesenquimais/citologia , Cabeça do Fêmur , Osteogênese , Células Cultivadas , Substitutos Ósseos/química , Durapatita/química , Fosfatos de Cálcio/químicaRESUMO
Bioactive and biodegradable scaffolds that mimic the natural extracellular matrix of bone serve as temporary structures to guide new bone tissue growth. In this study, 3D-printed scaffolds composed of poly (lactic acid) (PLA)-tricalcium phosphate (TCP) (90-10 wt.%) were modified with 1%, 5%, and 10 wt.% of ZnO to enhance bone tissue regeneration. A commercial chain extender named Joncryl was incorporated alongside ZnO to ensure the printability of the composites. Filaments were manufactured using a twin-screw extruder and subsequently used to print 3D scaffolds via fused filament fabrication (FFF). The scaffolds exhibited a homogeneous distribution of ZnO and TCP particles, a reproducible structure with 300 µm pores, and mechanical properties suitable for bone tissue engineering, with an elastic modulus around 100 MPa. The addition of ZnO resulted in enhanced surface roughness on the scaffolds, particularly for ZnO microparticles, achieving values up to 241 nm. This rougher topography was responsible for enhancing protein adsorption on the scaffolds, with an increase of up to 85% compared to the PLA-TCP matrix. Biological analyses demonstrated that the presence of ZnO promotes mesenchymal stem cell (MSC) proliferation and differentiation into osteoblasts. Alkaline phosphatase (ALP) activity, an important indicator of early osteogenic differentiation, increased up to 29%. The PLA-TCP composite containing 5% ZnO microparticles exhibited an optimized degradation rate and enhanced bioactivity, indicating its promising potential for bone repair applications.
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Materiais Biocompatíveis , Regeneração Óssea , Fosfatos de Cálcio , Diferenciação Celular , Proliferação de Células , Células-Tronco Mesenquimais , Osteoblastos , Poliésteres , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Óxido de Zinco , Alicerces Teciduais/química , Fosfatos de Cálcio/química , Poliésteres/química , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual/métodos , Células-Tronco Mesenquimais/citologia , Óxido de Zinco/química , Materiais Biocompatíveis/química , Diferenciação Celular/efeitos dos fármacos , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Teste de Materiais , Osso e Ossos , Regeneração Tecidual Guiada/métodos , Humanos , Animais , Fosfatase Alcalina/metabolismo , Módulo de Elasticidade , Porosidade , Propriedades de SuperfícieRESUMO
In this investigation, the electrospun nanocomposite scaffolds were developed utilizing poly-3-hydroxybutyrate (PHB), zein, and multiwalled carbon nanotubes (MWCNTs) at varying concentrations of MWCNTs including 0.5 and 1 wt%. Based on the SEM evaluations, the scaffold containing 1 wt% MWCNTs (PZ-1C) exhibited the lowest fiber diameter (384 ± 99 nm) alongside a suitable porosity percentage. The presence of zein and MWCNT in the chemical structure of the scaffold was evaluated by FTIR. Furthermore, TEM images revealed the alignment of MWCNTs with the fibers. Adding 1 % MWCNTs to the PHB-zein scaffold significantly enhanced tensile strength by about 69 % and reduced elongation by about 31 %. Hydrophilicity, surface roughness, crystallinity, and biomineralization were increased by incorporating 1 wt% MWCNTs, while weight loss after in vitro degradation was decreased. The MG-63 cells exhibited enhanced attachment, viability, ALP secretion, calcium deposition, and gene expression (COLI, RUNX2, and OCN) when cultivated on the scaffold containing MWCNTs compared to the scaffolds lacking MWCNTs. Moreover, the study found that MWCNTs significantly reduced platelet adhesion and hemolysis rates below 4 %, indicating their favorable anti-hemolysis properties. Regarding the aforementioned results, the PZ-1C electrospun composite scaffold is a promising scaffold with osteogenic properties for bone tissue engineering applications.
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Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their multi-potent potential and ability to generate a pro-regenerative secretome. While many have reported the influence of matrix environment on MSC osteogenic response, few have investigated the effects of donor and sex. Here, a well-defined mineralized collagen scaffold is used to study the influence of passage number and donor-reported sex on MSC proliferation and osteogenic potential. A library of bone marrow and adipose tissue-derived stem cells from eight donors to examine donor viability in osteogenic capacity in mineralized collagen scaffolds is obtained. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex-associated variability in osteogenic capacity. Notably, MSCs from male donors displayed significantly higher cell proliferation while MSCs from female donors displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. The study highlights the essentiality of including donor-reported sex as an experimental variable and reporting culture expansion in future studies of biomaterial regenerative potential.
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Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.
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In this study, hydroxyapatite (HAp) was synthesized from natural biowaste materials, specifically mussel shells, and combined with chitosan (CS) and gentamicin sulfate antibiotic (GA) using an in-situ method. The resulting composite material, designated HAp/CS-GA, has its physicochemical and structural properties characterized by Fourier transform infrared spectroscopy (FTIR) analysis. The drug-loaded structure was confirmed by UV-visible absorption spectroscopy (UV-Vis) and X-ray diffraction (XRD) analysis. Additionally, field emission scanning electron microscopy (FE-SEM) equipped with the energy dispersive X-ray spectroscopic (EDX) technique was used to determine the surface topography and main components. The composite of HAp/CS-GA was analyzed using a drug release profile and UV-visible spectroscopy (UV-Vis). The fabricated composites antimicrobial behavior was examined against bone infection-causing Gram-positive and Gram-negative bacteria, showing potential activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus compared to Escherichia coli, respectively. Simultaneously, the cytotoxicity of the composite was evaluated by MTT assay using an MG-63 osteoblast-like cell line that exhibited no toxicity in the prepared composite. After a 24â¯h incubation period, the MG-63 cells on the HAp/CS-GA composite showed good proliferation, according to Hoechst 33258 fluorescence staining results. The results suggested that the composite had excellent biocompatibility and antibacterial activity and enhanced the osteoblast cell proliferation. Therefore, the designed HAp/CS-GA composite would be a promising candidate for bone tissue engineering.
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Nowadays, as a result of the frequent occurrence of accidental injuries and traumas such as bone damage, the number of people causing bone injuries or fractures is increasing around the world. The design and fabrication of ideal bone tissue engineering (BTE) materials have become a research hotspot in the scientific community, and thus provide a novel path for the treatment of bone diseases. Among the materials used to construct scaffolds in BTE, including metals, bioceramics, bioglasses, biomacromolecules, synthetic organic polymers, etc., natural biopolymers have more advantages against them because they can interact with cells well, causing natural polymers to be widely studied and applied in the field of BTE. In particular, alginate has the advantages of excellent biocompatibility, good biodegradability, non-immunogenicity, non-toxicity, wide sources, low price, and easy gelation, enabling itself to be widely used as a biomaterial. However, pure alginate hydrogel as a BTE scaffold material still has many shortcomings, such as insufficient mechanical properties, easy disintegration of materials in physiological environments, and lack of cell-specific recognition sites, which severely limits its clinical application in BTE. In order to overcome the defects of single alginate hydrogels, researchers prepared alginate composite hydrogels by adding one or more materials to the alginate matrix in a certain proportion to improve their bioapplicability. For this reason, this review will introduce in detail the methods for constructing alginate composite hydrogels, including alginate/polymer composite hydrogels, alginate/bioprotein or polypeptide composite hydrogels, alginate/bioceramic composite hydrogels, alginate/bioceramic composite hydrogels, and alginate/nanoclay composite hydrogels, as well as their biological application trends in BTE scaffold materials, and look forward to their future research direction. These alginate composite hydrogel scaffolds exhibit both unexceptionable mechanical and biochemical properties, which exhibit their high application value in bone tissue repair and regeneration, thus providing a theoretical basis for the development and sustainable application of alginate-based functional biomedical materials.
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Alginatos , Materiais Biocompatíveis , Osso e Ossos , Hidrogéis , Engenharia Tecidual , Alicerces Teciduais , Alginatos/química , Engenharia Tecidual/métodos , Hidrogéis/química , Humanos , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Animais , Regeneração Óssea/efeitos dos fármacosRESUMO
Oxygen (O2)-delivering tissue substitutes have shown tremendous potential for enhancing tissue regeneration, maturation, and healing. As O2 is both a metabolite and powerful signaling molecule, providing controlled delivery is crucial for optimizing its beneficial effects in the treatment of critical-sized injuries. Here, we report the design and fabrication of 3D-printed, biodegradable, O2-generating bone scaffold comprising calcium peroxide (CPO) that once hydrolytically activated, provides long-term generation of oxygen at a controlled, concentration-dependent manner, and polycaprolactone (PCL), a hydrophobic polymer that regulate the interaction of CPO with water, preventing burst release of O2 at early time points. When anoxic conditions were simulated in vitro, CPO-PCL scaffolds maintained the survival and proliferation of human adipose-derived stem/stromal cells (hASCs) relative to PCL-only controls. We assessed the in vivo osteogenic efficacy of hASC-seeded CPO-PCL scaffolds implanted in a non-healing critical-sized 4-mm calvarial defects in nude mice for 8 weeks. Even without exogenous osteoinductive factors, CPO-PCL scaffolds demonstrated increased new bone volume compared to PCL-only scaffolds as verified by both microcomputed tomography analysis and histological assessments. Lastly, we employed a quantitative 3D lightsheet microscopy platform to determine that O2-generating scaffolds had similar vascular volumes with slightly higher presence of CD31hiEmcnhi pro-osteogenic, type H vessels and increased number of Osterix+ skeletal progenitor cells relative to PCL-only scaffolds. In summary, 3D-printed O2 generating CPO-PCL scaffolds with tunable O2 release rates provide a facile, customizable strategy for effectively treating, craniofacial bone defects. STATEMENT OF SIGNIFICANCE: Oxygen(O2)-delivering bone substitutes show promise in defect repair applications by supplying O2 to the cells within or around the graft, improving cell survivability and enhancing bone matrix mineralization. A novel O2-generating bone scaffold has been 3D printed for the first-time which ensures patient and defect specificity. 3D printed calcium peroxide-polycaprolactone (CPO-PCL) bone scaffold provides uninterrupted O2 supply for 22 days allowing cell survival in deprived O2 and nutrient conditions. For the first time, O2-driven bone regenerative environment in mice calvaria has been captured by light-sheet imaging which illuminates abundance of Osterix+ cells, angiogenesis at a single cell resolution indicating active site of bone remodeling and growth in the presence of O2.
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The aim of this study is to provide an overview of the current state-of-the-art in the fabrication of bioceramic scaffolds for bone tissue engineering, with an emphasis on the use of three-dimensional (3D) technologies coupled with generative design principles. The field of modern medicine has witnessed remarkable advancements and continuous innovation in recent decades, driven by a relentless desire to improve patient outcomes and quality of life. Central to this progress is the field of tissue engineering, which holds immense promise for regenerative medicine applications. Scaffolds are integral to tissue engineering and serve as 3D frameworks that support cell attachment, proliferation, and differentiation. A wide array of materials has been explored for the fabrication of scaffolds, including bioceramics (i.e., hydroxyapatite, beta-tricalcium phosphate, bioglasses) and bioceramic-polymer composites, each offering unique properties and functionalities tailored to specific applications. Several fabrication methods, such as thermal-induced phase separation, electrospinning, freeze-drying, gas foaming, particle leaching/solvent casting, fused deposition modeling, 3D printing, stereolithography and selective laser sintering, will be introduced and thoroughly analyzed and discussed from the point of view of their unique characteristics, which have proven invaluable for obtaining bioceramic scaffolds. Moreover, by highlighting the important role of generative design in scaffold optimization, this review seeks to pave the way for the development of innovative strategies and personalized solutions to address significant gaps in the current literature, mainly related to complex bone defects in bone tissue engineering.