ZIC1 Dictates Osteogenesis Versus Adipogenesis in Human Mesenchymal Progenitor Cells Via a Hedgehog Dependent Mechanism.

Numerous intrinsic factors regulate mesenchymal progenitor commitment to a specific cell fate, such as osteogenic or adipogenic lineages. Identification and modulation of novel intrinsic regulatory factors represent an opportunity to harness the regenerative potential of mesenchymal progenitors. In the present study, the transcription factor (TF) ZIC1 was identified to be differentially expressed among adipose compared with skeletal-derived mesenchymal progenitor cells. We observed that ZIC1 overexpression in human mesenchymal progenitors promotes osteogenesis and prevents adipogenesis. ZIC1 knockdown demonstrated the converse effects on cell differentiation. ZIC1 misexpression was associated with altered Hedgehog signaling, and the Hedgehog antagonist cyclopamine reversed the osteo/adipogenic differentiation alterations associated with ZIC1 overexpression. Finally, human mesenchymal progenitor cells with or without ZIC1 overexpression were implanted in an ossicle assay in NOD-SCID gamma mice. ZIC1 overexpression led to significantly increased ossicle formation in comparison to the control, as assessed by radiographic and histologic measures. Together, these data suggest that ZIC1 represents a TF at the center of osteo/adipogenic cell fate determinations-findings that have relevance in the fields of stem cell biology and therapeutic regenerative medicine.

ß-glycerophosphate, not low magnitude fluid shear stress, increases osteocytogenesis in the osteoblast-to-osteocyte cell line IDG-SW3.

AIM: As osteoblasts deposit a mineralized collagen network, a subpopulation of these cells differentiates into osteocytes. Biochemical and mechanical stimuli, particularly fluid shear stress (FSS), are thought to regulate this, but their relative influence remains unclear. Here, we assess both biochemical and mechanical stimuli on long-term bone formation and osteocytogenesis using the osteoblast-osteocyte cell line IDG-SW3. METHODS: Due to the relative novelty and uncommon culture conditions of IDG-SW3 versus other osteoblast-lineage cell lines, effects of temperature and media formulation on matrix deposition and osteocytogenesis were initially characterized. Subsequently, the relative influence of biochemical (ß-glycerophosphate (ßGP) and ascorbic acid 2-phosphate (AA2P)) and mechanical stimulation on osteocytogenesis was compared, with intermittent application of low magnitude FSS generated by see-saw rocker. RESULTS: ßGP and AA2P supplementation were required for mineralization and osteocytogenesis, with 33°C cultures retaining a more osteoblastic phenotype and 37°C cultures undergoing significantly higher osteocytogenesis. ßGP concentration positively correlated with calcium deposition, whilst AA2P stimulated alkaline phosphatase (ALP) activity and collagen deposition. We demonstrate that increasing ßGP concentration also significantly enhances osteocytogenesis as quantified by the expression of green fluorescent protein linked to Dmp1. Intermittent FSS (~0.06 Pa) rocker had no effect on osteocytogenesis and matrix deposition. CONCLUSIONS: This work demonstrates the suitability and ease with which IDG-SW3 can be utilized in osteocytogenesis studies. IDG-SW3 mineralization was only mediated through biochemical stimuli with no detectable effect of low magnitude FSS. Osteocytogenesis of IDG-SW3 primarily occurred in mineralized areas, further demonstrating the role mineralization of the bone extracellular matrix has in osteocyte differentiation.

Ultrasound stimulated piezoelectric barium titanate and boron nitride nanotubes in nonconductive poly-ε-caprolactone nanofibrous scaffold for bone tissue engineering.

Nanomaterials can provide unique solutions for the problems experienced in tissue engineering by improving a scaffold's physico-bio-chemical properties. With its piezoelectric property, bone is an active tissue with easy adaptation and remodeling through complicated mechanisms of electromechanical operations. Although poly(ε-caprolactone) (PCL) is an excellent polymer for bone tissue engineering, it is lack of conductivity. In this study, piezoelectric barium titanates (BaTiO3) and boron nitride nanotubes (BNNTs) are used as ultrasound (US) stimulated piezoelectric components in PCL to mimic piezoelectric nature of bone tissue. Electric-responsive Human Osteoblast cells on the scaffolds were stimulated by applying low-frequency US during cell growth. Biocompatibility, cell adhesion, alkaline phosphatase activities and mineralization of osteoblast cells on piezo-composite scaffolds were investigated. BaTiO3or BNNTs as reinforcement agents improved physical and mechanical properties of PCL scaffolds.In vitrostudies show that the use of BaTiO3or BNNTs as additives in non-conductive scaffolds significantly induces and increases the osteogenic activities even without US stimulation. Although BaTiO3is one of the best piezoelectric materials, the improvement is more dramatic in the case of BNNTs with the increased mineralization, and excellent chemical and mechanical properties.

Ca-AlN MOFs-loaded chitosan/gelatin scaffolds; a dual-delivery system for bone tissue engineering applications.

Creating a scaffold for bone tissue engineering that is bioactive and capable of acting as a local-dual delivery system, releasing bioactive molecules and regulating the bone remodeling process to achieve balanced bone resorption and formation, is a significant challenge. The objective of this research is to create a composite scaffold using chitosan/gelatin (CHS/Gel) and the calcium (Ca)-alendronate (ALN) metal-organic frameworks (MOFs). The scaffold will act as a dual-delivery system, releasing Ca ions and ALN to regulate bone formation. Ca-ALN MOF nanoparticles (NPs) were prepared in mild conditions and studied by FTIR, XRD, FESEM, and TGA. Ca-ALN NPs-loaded CHS/Gel scaffolds were opportunely fabricated through freeze-drying approach. Physicochemical features of the scaffolds after incorporating NPs equated by CHS/Gel scaffold changed, therefore, the attendance of NPs caused a decreasing porosity, decreased swelling, and low rate of degradation. The release profile results showed that the NPs-loaded CHS/Gel scaffolds were able to simultaneously release ALN and Ca ions due to the decomposition of NPs. Additionally, the loading of NPs in the CHS/Gel scaffold led to an increment in alkaline phosphatase (ALP) activity and the quantity of deposited Ca along with osteogenesis gene markers. These findings suggest that the NPs-loaded CHS/Gel scaffold has the potential to enhance the differentiation of human adipose tissue-derived mesenchymal stem cells, making it a promising approach for bone repair.

Harnessing potential of avian eggshell membrane derived collagen hydrolysate for bone tissue regeneration.

BACKGROUND: Natural bone grafts are the highly preferred materials for restoring the lost bone, while being constrained of donor availability and risk of disease transmission. As a result, tissue engineering is emerging as an efficacious and competitive technique for bone repair. Bone tissue engineering (TE) scaffolds to support bone regeneration and devoid of aforesaid limitations are being vastly explored and among these the avian eggshell membrane has drawn attention for TE owing to its low immunogenicity, similarity with the extracellular matrix, and easy availability. METHODOLOGY AND RESULTS: In this study, the development of bone ingrowth support system from avian eggshell membrane derived collagen hydrolysates (Col-h) is reported. The hydrolysate, cross-linked with glutaraldehyde, was developed into hydrogels with poly-(vinyl alcohol) (PVA) by freeze-thawing and further characterized with ATR-FTIR, XRD, FESEM. The biodegradability, swelling, mechanical, anti-microbial, and biocompatibility evaluation were performed further for the suitability in bone regeneration. The presence of amide I, amide III, and -OH functional groups at 1639 cm- 1,1264 cm- 1, and 3308 cm- 1 respectively and broad peak between 16°-21° (2θ) in XRD data reinstated the composition and form. CONCLUSIONS: The maximum ratio of Col-h/PVA that produced well defined hydrogels was 50:50. Though all the hydrogel matrices alluded towards their competitive attributes and applicability towards restorative bone repair, the hydrogel with 40:60 ratios showed better mechanical strength and cell proliferation than its counterparts. The prominent E. coli growth inhibition by the hydrogel matrices was also observed, along with excellent biocompatibility with MG-63 osteoblasts. The findings indicate strongly the promising application of avian eggshell-derived Col-h in supporting bone regeneration.

The use of mesenchymal stromal cell secretome to enhance guided bone regeneration in comparison with leukocyte and platelet-rich fibrin.

OBJECTIVES: Secretomes of mesenchymal stromal cells (MSC) represent a novel strategy for growth-factor delivery for tissue regeneration. The objective of this study was to compare the efficacy of adjunctive use of conditioned media of bone-marrow MSC (MSC-CM) with collagen barrier membranes vs. adjunctive use of conditioned media of leukocyte- and platelet-rich fibrin (PRF-CM), a current growth-factor therapy, for guided bone regeneration (GBR). METHODS: MSC-CM and PRF-CM prepared from healthy human donors were subjected to proteomic analysis using mass spectrometry and multiplex immunoassay. Collagen membranes functionalized with MSC-CM or PRF-CM were applied on critical-size rat calvaria defects and new bone formation was assessed via three-dimensional (3D) micro-CT analysis of total defect volume (2 and 4 weeks) and 2D histomorphometric analysis of central defect regions (4 weeks). RESULTS: While both MSC-CM and PRF-CM revealed several bone-related proteins, differentially expressed proteins, especially extracellular matrix components, were increased in MSC-CM. In rat calvaria defects, micro-CT revealed greater total bone coverage in the MSC-CM group after 2 and 4 weeks. Histologically, both groups showed a combination of regular new bone and 'hybrid' new bone, which was formed within the membrane compartment and characterized by incorporation of mineralized collagen fibers. Histomorphometry in central defect sections revealed greater hybrid bone area in the MSC-CM group, while the total new bone area was similar between groups. CONCLUSION: Based on the in vitro and in vivo investigations herein, functionalization of membranes with MSC-CM represents a promising strategy to enhance GBR.

Porous Mg-Zn-Ca scaffolds for bone repair: a study on microstructure, mechanical properties and in vitro degradation behavior.

Biodegradable porous Mg scaffolds are a promising approach to bone repair. In this work, 3D-spherical porous Mg-1.5Zn-0.2Ca (wt.%) scaffolds were prepared by vacuum infiltration casting technology, and MgF2 and fluorapatite coatings were designed to control the degradation behavior of Mg-based scaffolds. The results showed that the pores in Mg-based scaffolds were composed of the main spherical pores (450-600 µm) and interconnected pores (150-200 µm), and the porosity was up to 74.97%. Mg-based porous scaffolds exhibited sufficient mechanical properties with a compressive yield strength of about 4.04 MPa and elastic modulus of appropriately 0.23 GPa. Besides, both MgF2 coating and fluorapatite coating could effectively improve the corrosion resistance of porous Mg-based scaffolds. In conclusion, this research would provide data support and theoretical guidance for the application of biodegradable porous Mg-based scaffolds in bone tissue engineering.

3D-printed polycaprolactone scaffolds coated with beta tricalcium phosphate for bone regeneration.

BACKGROUND/PURPOSE: 3D-printing technology is an important tool for the bone tissue engineering (BTE). The aim of this study was to investigate the interaction of polycaprolactone (PCL) scaffolds and modified mesh PCL coated with beta TCP (PCL/ß-TCP) scaffolds with MG-63. METHODS: This study used the fused deposition modeling (FDM) technique with the 3D printing technique to fabricate the thermoplastic polymer and composite scaffolds. Scaffold structure and coating quality were observed under a scanning electron microscope (SEM). MG-63 cells were injected and attached to the mesh-manufactured PCL scaffolds. The biocompatibility of mesh structured PCL and PCL/ß-TCP scaffolds could be examined by measuring the viability of MG-63 cells of MTT assay. Bone cell differentiation was evaluated ALP activity by mineralization assay. RESULTS: The results showed that both mesh PCL scaffolds and PCL/ß-TCP scaffolds were non-toxic to the cells. The ALP activities of cells in PCL/ß-TCP scaffolds groups were significant differences and better than PCL groups in all groups at all experimental dates. The mineralization process was time-dependent, and significantly higher mineralization of osteosarcoma cells was observed on PCL/ß-TCP scaffolds at experimental dates. CONCLUSION: We concluded that both meshes structured PCL and PCL/ß-TCP scaffolds could promote the MG-63 cell growth, and PCL/ß-TCP was better than the PCL scaffolds for the outcome of MG63 cell differentiation and mineralization.

Bone tissue regeneration by 58S bioactive glass scaffolds containing exosome: an in vivo study.

Exosomes, the naturally secreted nanocarriers of cells, have recently been demonstrated to have therapeutic benefits in a variety of disease models where parent cells are not present. However, the use of exosomes in bone defect regeneration has been unusual, and little is documented about the underlying processes. In recent study we produced and characterized exosomes derived human endometrial mesenchymal stem stromal cells and 58S bioactive glass scaffolds; in following, in this research exosome loaded scaffolds synthetized and release of exosome, porosity and bioactivity of them were assessed. More over the effect of scaffolds on repair of critical-size bone defects in rat's calvaria was evaluated by histological examination and micro computed tomography (µ CT). The findings confirmed that constructed porous scaffolds consistently release exosomes; additionally, in vivo findings including Hematoxilin & Eosin staining, Immunohistochemistry, Masson's trichrome, histomorphometric analysis, and µ CT clarified that our implant has osteogenic properties. We discovered that Exo-treated scaffolds might promote osteogenesis especially compared to pure scaffolds, indicating that produced scaffolds containing exosomes could be a potential replacement in bone tissue engineering.

Enhanced Electroactive Phases of Poly(vinylidene Fluoride) Fibers for Tissue Engineering Applications.

Nanofibrous materials generated through electrospinning have gained significant attention in tissue regeneration, particularly in the domain of bone reconstruction. There is high interest in designing a material resembling bone tissue, and many scientists are trying to create materials applicable to bone tissue engineering with piezoelectricity similar to bone. One of the prospective candidates is highly piezoelectric poly(vinylidene fluoride) (PVDF), which was used for fibrous scaffold formation by electrospinning. In this study, we focused on the effect of PVDF molecular weight (180,000 g/mol and 530,000 g/mol) and process parameters, such as the rotational speed of the collector, applied voltage, and solution flow rate on the properties of the final scaffold. Fourier Transform Infrared Spectroscopy allows for determining the effect of molecular weight and processing parameters on the content of the electroactive phases. It can be concluded that the higher molecular weight of the PVDF and higher collector rotational speed increase nanofibers' diameter, electroactive phase content, and piezoelectric coefficient. Various electrospinning parameters showed changes in electroactive phase content with the maximum at the applied voltage of 22 kV and flow rate of 0.8 mL/h. Moreover, the cytocompatibility of the scaffolds was confirmed in the culture of human adipose-derived stromal cells with known potential for osteogenic differentiation. Based on the results obtained, it can be concluded that PVDF scaffolds may be taken into account as a tool in bone tissue engineering and are worth further investigation.

Recent Advancements in Bone Tissue Engineering: Integrating Smart Scaffold Technologies and Bio-Responsive Systems for Enhanced Regeneration.

In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems.

Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration.

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.

Development of Bioactive Hybrid Poly(lactic acid)/Poly(methyl methacrylate) (PLA/PMMA) Electrospun Fibers Functionalized with Bioglass Nanoparticles for Bone Tissue Engineering Applications.

Hybrid scaffolds that are based on PLA and PLA/PMMA with 75/25, 50/50, and 25/75 weight ratios and functionalized with 10 wt.% of bioglass nanoparticles (n-BG) were developed using an electrospinning technique with a chloroform/dimethylformamide mixture in a 9:1 ratio for bone tissue engineering applications. Neat PLA and PLA/PMMA hybrid scaffolds were developed successfully through a (CF/DMF) solvent system, obtaining a random fiber deposition that generated a porous structure with pore interconnectivity. However, with the solvent system used, it was not possible to generate fibers in the case of the neat PMMA sample. With the increase in the amount of PMMA in PLA/PMMA ratios, the fiber diameter of hybrid scaffolds decreases, and the defects (beads) in the fiber structure increase; these beads are associated with a nanoparticle agglomeration, that could be related to a low interaction between n-BG and the polymer matrix. The Young's modulus of PLA/PMMA/n-BG decreases by 34 and 80%, indicating more flexible behavior compared to neat PLA. The PLA/PMMA/n-BG scaffolds showed a bioactive property related to the presence of hydroxyapatite crystals in the fiber surface after 28 days of immersion in a Simulated Body Fluids solution (SBF). In addition, the hydrolytic degradation process of PLA/PMMA/n-BG, analyzed after 35 days of immersion in a phosphate-buffered saline solution (PBS), was less than that of the pure PLA. The in vitro analysis using an HBOF-1.19 cell line indicated that the PLA/PMMA/n-BG scaffold showed good cell viability and was able to promote cell proliferation after 7 days. On the other hand, the in vivo biocompatibility evaluated via a subdermal model in BALC male mice corroborated the good behavior of the scaffolds in avoiding the generation of a cytotoxic effect and being able to enhance the healing process, suggesting that the materials are suitable for potential applications in tissue engineering.

An Overview on the Big Players in Bone Tissue Engineering: Biomaterials, Scaffolds and Cells.

Presently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection. To surmount these challenges, tissue engineering has emerged as a promising avenue for bone injury repair and reconstruction. It involves the use of different biomaterials and the development of three-dimensional porous matrices and scaffolds, alongside osteoprogenitor cells and growth factors to stimulate natural tissue regeneration. This review compiles methodologies that can be used to develop biomaterials that are important in bone tissue replacement and regeneration. Biomaterials for orthopedic implants, several scaffold types and production methods, as well as techniques to assess biomaterials' suitability for human use-both in laboratory settings and within living organisms-are discussed. Even though researchers have had some success, there is still room for improvements in their processing techniques, especially the ones that make scaffolds mechanically stronger without weakening their biological characteristics. Bone tissue engineering is therefore a promising area due to the rise in bone-related injuries.

Multilayer Electrospun Scaffolds of Opposite-Charged Chitosans.

Chitosan (CS) is a polysaccharide obtainable by the deacetylation of chitin, which is highly available in nature and is consequently low-cost. Chitosan is already used in the biomedical field (e.g., guides for nerve reconstruction) and has been proposed as a biomaterial for tissue regeneration in different body districts, including bone tissue. The interest in chitosan as a biomaterial stems from its ease of functionalization due to the presence of reactive groups, its antibacterial properties, its ease of processing to obtain porous matrices, and its inherent similarity to polysaccharides that constitute the human extracellular matrix, such as hyaluronic acid (HA). Here, chitosan was made to react with succinic anhydride to develop a negatively charged chitosan (SCS) that better mimics HA. FT-IR and NMR analyses confirmed the presence of the carboxylic groups in the modified polymer. Four different electrospun matrices were prepared: CS, SCS, a layer-by-layer matrix (LBL), and a matrix with both CS and SCS simultaneously electrospun (HYB). All the matrices containing SCS showed increased human osteoblast proliferation, mineralization, and gene expression, with the best results obtained with HYB compared to the control (CS). Moreover, the antibacterial potential of CS was preserved in all the SCS-containing matrices, and the pure SCS matrix demonstrated a significant reduction in bacterial proliferation of both S. aureus and E. coli.

Functionalization of Ceramic Scaffolds with Exosomes from Bone Marrow Mesenchymal Stromal Cells for Bone Tissue Engineering.

The functionalization of bone substitutes with exosomes appears to be a promising technique to enhance bone tissue formation. This study investigates the potential of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) to improve bone healing and bone augmentation when incorporated into wide open-porous 3D-printed ceramic Gyroid scaffolds. We demonstrated the multipotent characteristics of BMSCs and characterized the extracted exosomes using nanoparticle tracking analysis and proteomic profiling. Through cell culture experimentation, we demonstrated that BMSC-derived exosomes possess the ability to attract cells and significantly facilitate their differentiation into the osteogenic lineage. Furthermore, we observed that scaffold architecture influences exosome release kinetics, with Gyroid scaffolds exhibiting slower release rates compared to Lattice scaffolds. Nevertheless, in vivo implantation did not show increased bone ingrowth in scaffolds loaded with exosomes, suggesting that the scaffold microarchitecture and material were already optimized for osteoconduction and bone augmentation. These findings highlight the lack of understanding about the optimal delivery of exosomes for osteoconduction and bone augmentation by advanced ceramic scaffolds.

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Bacterial cellulose (BC) is a type of extracellular polymeric nanomaterial secreted by microorganisms over the course of their growth. It has gained significant attention in the field of bone tissue engineering due to its unique structure of three-dimensional fibrous network, excellent biocompatibility, biodegradability, and exceptional mechanical properties. Nevertheless, BC still has some weaknesses, including low osteogenic activity, a lack of antimicrobial properties, small pore size, issues with the degradation rate, and a mismatch in bone tissue regeneration, limiting its standalone use in the field of bone tissue engineering. Therefore, the modification of BC and the preparation of BC composite materials have become a recent research focus. Herein, we summarized the relationships between the production, modification, and bone repair applications of BC. We introduced the methods for the preparation and the modification of BC. Additionally, we elaborated on the new advances in the application of BC composite materials in the field of bone tissue engineering. We also highlighted the existing challenges and future prospects of BC composite materials.

Advances in biomimetic collagen mineralisation and future approaches to bone tissue engineering.

With an ageing world population and ~20% of adults in Europe being affected by bone diseases, there is an urgent need to develop advanced regenerative approaches and biomaterials capable to facilitate tissue regeneration while providing an adequate microenvironment for cells to thrive. As the main components of bone are collagen and apatite mineral, scientists in the tissue engineering field have attempted in combining these materials by using different biomimetic approaches to favour bone repair. Still, an ideal bone analogue capable of mimicking the distinct properties (i.e., mechanical properties, degradation rate, porosity, etc.) of cancellous bone is to be developed. This review seeks to sum up the current understanding of bone tissue mineralisation and structure while providing a critical outlook on the existing biomimetic strategies of mineralising collagen for bone tissue engineering applications, highlighting where gaps in knowledge exist.

Characterization of three-dimensional bone-like tissue growth and organization under influence of directional fluid flow.

The transition in the field of bone tissue engineering from bone regeneration to in vitro models has come with the challenge of recreating a dense and anisotropic bone-like extracellular matrix (ECM). Although the mechanism by which bone ECM gains its structure is not fully understood, mechanical loading and curvature have been identified as potential contributors. Here, guided by computational simulations, we evaluated cell and bone-like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human mesenchymal stromal cells were seeded on donut-shaped silk fibroin scaffolds and osteogenically stimulated for 42 days statically or in a flow perfusion bioreactor. After 14, 28, and 42 days, constructs were investigated for cell and tissue growth and organization. As a result, directional fluid flow was able to improve organic tissue growth but not organization. Cells tended to orient in the tangential direction of the channel, possibly attributed to its curvature. Based on our results, we suggest that organic ECM production but not anisotropy can be stimulated through the application of fluid flow. With this study, an initial attempt in three-dimensions was made to improve the resemblance of in vitro produced bone-like ECM to the physiological bone ECM.

Ion incorporation into bone grafting materials.

The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.