Synthetic helical peptides on nanofibers to activate cell-surface receptors and synergistically enhance critical-sized bone defect regeneration.

More than 500,000 bone grafting procedures are performed annually in the USA. Considering the significant limitations of available bone grafts, we previously invented a phase-separation technology to generate nanofibrous poly(l-lactic acid) (PLLA) scaffolds that mimic the bone matrix collagen in nanofiber geometry and enhance bone regeneration. Here we report the development of nanofibrous scaffolds with covalently attached synthetic peptides that mimic native collagen peptides to activate the two main collagen receptors in bone cells, discoidin domain receptor 2 (DDR2) and ß1 integrins. We synthesized a PLLA-based graft-copolymer to enable covalent peptide conjugation via a click reaction. Using PLLA and the graft-copolymer, we developed 3D scaffolds with interconnected pores and peptides-containing nanofibers to activate DDR2 and ß1 integrins of osteogenic cells. The degradation rate and mechanical properties of the scaffolds are tunable. The peptides-decorated nanofibrous scaffolds demonstrated 7.8 times more mineralized bone regeneration over the control scaffolds without the peptides in a critical-sized bone defect regeneration model after 8 weeks of implantation, showing a synergistic effect of the two peptides. This study demonstrates the power of scaffolds to mimic ECM at both nanometer and molecular levels, activating cell surface receptors to liberate the innate regenerative potential of host stem/progenitor cells.

Metal-organic frameworks (MOFs) and their derivatives as emerging biomaterials for the treatment of osteoarthritis.

As a novel class of smart biomaterials with promising potentials, metal-organic frameworks (MOFs) are widely utilized in the field of biomedicine. Current researches indicate that the therapeutic strategies for osteoarthritis (OA) are highly limited to achieving symptom improvement and reducing both pain and inflammation. Together, the introduction of MOFs into the treatment of OA holds the potential to offer significant benefits. This is because MOFs not only have intrinsic biological activities, but also act as carriers to facilitate controlled drug delivery and prolong the duration in the management of OA. This paper presents a review of the recent studies that have explored the potential usage of MOFs as drugs or carriers in the treatment of OA, which also examines the progress of MOFs in tissue engineering for the treatment of OA. These studies are anticipated to not only enhance the comprehension of MOFs but also provide strong evidence in favor of their utilization in the treatment of OA.

3D printed polylactic acid/polyethylene glycol/bredigite nanocomposite scaffold enhances bone tissue regeneration via promoting osteogenesis and angiogenesis.

Recently, the fabrication of personalized scaffolds with high accuracy has been developed through 3D printing technology. In the current study, polylactic acid/polyethylene glycol (PLA/PEG) composite scaffolds with varied weight percentages (0, 5, 10, 20 and 30 %) of bredigite nanoparticles (B) were fabricated using the 3D printing and then characterized through scanning electron microscopy and Fourier transform infra-red spectroscopy. The addition of B nanoparticles up to 20 wt% to PLA/PEG scaffold increased the compressive strength (from 7.59 to 13.84 MPa) and elastic modulus (from 142.42 to 268.33 MPa). The apatite formation ability as well as inorganic ion release in simulated body fluid were investigated for 28 days. The MG-63 cells viability and adhesion were enhanced by increasing the amount of B in the PLA/PEG scaffold and the osteogenic differentiation of the rat bone marrow mesenchymal stem cells was confirmed by alkaline phosphatase activity test and alizarin red staining. According to chorioallantoic membrane assay, the highest angiogenesis occurred around the PLA/PEG/B30 scaffold. In vivo experiments on a rat calvarial defect model demonstrated an almost complete recovery in the PLA/PEG/B30 group within 8 weeks. Based on the results, the PLA/PEG/B30 composite scaffold is proposed as an optimal scaffold to repair bone defects.

Fabrication and characterization of nanohydroxyapatite/chitosan/decellularized placenta scaffold for bone tissue engineering applications.

Novel biomaterials are necessary to fabricate biomimetic scaffolds for bone tissue engineering. In the present experiment, we aimed to fabricate and evaluate the osteogenic properties of nanohydroxyapatite/chitosan/decellularized placenta (nHA.Cs.dPL) composite scaffolds. The human placenta was decellularized (dPL), characterized, and digested in pepsin to form the hydrogel. nHA.Cs.dPL scaffolds were fabricated using salt leaching/freeze drying and evaluated for their morphology, chemical composition, swelling, porosity, degradation, mechanical strength, and biocompatibility. Saos-2 cells were seeded on scaffolds, and their osteogenic properties were investigated by evaluating alkaline phosphatase (ALP), osteocalcin (OCN), collagen type 1 (COL I) expression, and calcium deposition under osteogenic differentiation. The dPL was prepared with minimized DNA content and a well-preserved porous structure. Scaffolds were highly porous with interconnected pores and exhibited appropriate swelling and degradation rates supporting saos-2 cell attachment and proliferation. dPL improved scaffold physicochemical features and increased cell proliferation, ALP, OCN, COL I expression, and calcium deposition under osteogenic differentiation induction. nHA.Cs.dPL composite scaffolds provide a 3D microenvironment with superior physicochemical features that support saos-2 cell adhesion, proliferation, and osteogenic differentiation.

Determination of the Optimum Architecture of Additively Manufactured Magnetic Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug-Delivery Applications.

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm3 dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO2, 20% Na2O, 23% CaO, 6% P2O5, 2.5% B2O3, 1% ZnO, 2% MgO, and 0.5% CaF2 (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Microfluidic Fabrication of Gelatin-Nano Hydroxyapatite Scaffolds for Enhanced Control of Pore Size Distribution and Osteogenic Differentiation of Dental Pulp Stem Cells.

The combination of gelatin and hydroxyapatite (HA) has emerged as a promising strategy in dental tissue engineering due to its favorable biocompatibility, mechanical properties, and ability to support cellular activities essential for tissue regeneration, rendering them ideal components for hard tissue applications. Besides, precise control over interconnecting porosity is of paramount importance for tissue engineering materials. Conventional methods for creating porous scaffolds frequently encounter difficulties in regulating pore size distribution. This study demonstrates the fabrication of gelatin-nano HA scaffolds with uniform porosity using a T-type junction microfluidic device in a single-step process. Significant improvements in control over the pore size distribution are achieved by regulating the flow parameters, resulting in effective and time-efficient manufacturing comparable in quality to the innovative 3D bioprinting techniques. The overall porosity of the scaffolds exceeded 60%, with a remarkably narrow size distribution. The incorporation of nano-HAinto 3D porous gelatin scaffolds successfully induced osteogenic differentiation in stem cells at both the protein and gene levels, as evidenced by the significant increase in osteocalcin (OCN), an important marker of osteogenic differentiation. The OCN levels are 26 and 43 times higher for gelatin and gelatin-HA scaffolds, respectively, compared to the control group.

Synergetic effect of bioglass and nano montmorillonite on 3D printed nanocomposite of polycaprolactone/gelatin in the fabrication of bone scaffolds.

Nowadays, bone injuries and disorders have increased all over the world and can reduce the quality of human life. Bone tissue engineering repair approaches require new biomaterials and methods to construct scaffolds with the required structural properties as well as improved performance. As potential therapeutic strategies in bone tissue engineering, 3D printed scaffolds have been developed. Polycaprolactone/Ceramic composites have attracted considerable attention due to their cytocompatibility, biodegradability, and physical properties. In this study, a 3D printing process was used to create polycaprolactone (PCL)-Gelatin (GEL) scaffolds containing varying concentrations of Bioglass (BG) and Nano Montmorillonite (MMT). This mixture was then loaded into a 3D printer, and the scaffolds were printed layer by layer. After constructing the scaffolds, they were then examined for their physical, chemical, and biological characteristics. Surface appearance was analyzed with a scanning electron microscope (SEM), which revealed that NC increased the diameter of pores from 465 to 480 µm. The elements in the scaffolds were evaluated by EDX analysis, and a uniform dispersion of nano montmorillonite particles was observed. The compressive strength reached 76.43 MPa for PCL/G/35 %MMT/15 %BG scaffold. Also, the rate of water absorption, biodegradability and bioactivity of PCL-GEL scaffolds increased significantly in the presence of NC. According to the MTT cell test results, adding BG and NC increased cell proliferation, adhesion and cell viability to 127.7 %. These findings indicated that the 3D printed PCL/G/35 %MMT/15 %BG scaffold has promising strategies for bone repair applications. Also, polynomial curve fitting shows that scaffold degradability after soaking in PBS can be predicted using the initial weight and soaking time. Adding more variables and data could improve prediction accuracy, reducing the need for experiments and conserving resources.

Fabrication of 3D microfibrous composite polycaprolactone/hydroxyapatite scaffolds loaded with piezoelectric poly (lactic acid) nanofibers by sequential near-field and conventional electrospinning for bone tissue engineering.

Near-field electrospinning (NFES) has recently gained considerable interest in fabricating tissue engineering scaffolds. This technique combines the advantages of both 3D printing and electrospinning. It allows for the production of fibers with smaller resolution and the ability to make regular structures with suitable pores. In this study, a microfibrous composite scaffold of polycaprolactone (PCL)/hydroxyapatite (HA) was prepared by NFES in the first step. The microfibrous scaffold had a fiber spacing of 414.674 ± 24.9 µm with an average fiber diameter of 94.695 ± 16.149 µm. However, due to the large fiber spacing, the surface area was insufficient for cell adhesion. Therefore, the hybrid scaffold was prepared by adding aligned and random electrospun poly (L-lactic acid) (PLLA) nanofibers to the microfibrous scaffold. Cellular studies showed that cell adhesion to the hybrid scaffold increased by 334 % compared to the microfibrous scaffold. These nanofibers also exhibited piezoelectric properties, which helped stimulate bone regeneration. Aligned nanofibers in the hybrid scaffold enhanced alkaline phosphatase activity and the intensity of alizarin red staining 1.5 and 1.6 times, respectively, compared to the microfibrous scaffold. Furthermore, the elastic modulus and ultimate tensile strength increased by 268 % and 130 %, respectively, by adding aligned nanofibers to the microfibrous scaffold. Therefore, the hybrid microfibrous composite scaffold of PCL/HA containing aligned electrospun PLLA nanofibers with improved properties showed the potential for bone regeneration.

Multilayer Gelatin-Supported BMP-9 Coating Promotes Osteointegration and Neo-Bone Formation at the n-CDHA/PAA Composite Biomaterial-Bone Interface.

BACKGROUND: The development of biomaterials capable of accelerating bone wound repair is a critical focus in bone tissue engineering. This study aims to evaluate the osteointegration and bone regeneration potential of a novel multilayer gelatin-supported Bone Morphogenetic Protein 9 (BMP-9) coated nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) composite biomaterials, focusing on the material-bone interface, and putting forward a new direction for the research on the interface between the coating material and bone. METHODS: The BMP-9 recombinant adenovirus (Adenovirus (Ad)-BMP-9/Bone Marrow Mesenchymal Stem Cells (BMSc)) was produced by transfecting BMSc and supported using gelatin (Ad-BMP-9/BMSc/Gelatin (GT). Multilayer Ad-BMP-9/BMSc/GT coated nano-calcium deficient hydroxyapatite/polyamino acid (n-CDHA/PAA) composite biomaterials were then prepared and co-cultured with MG63 cells for 10 days, with biocompatibility assessed through microscopy, Cell Counting Kit-8 (CCK-8), and alkaline phosphatase (ALP) assays. Subsequently, multilayer Ad-BMP-9/BMSc/GT coated n-CDHA/PAA composite biomaterial screws were fabricated, and the adhesion of the coating to the substrate was observed using scanning electron microscopy (SEM). In vivo studies were conducted using a New Zealand White rabbit intercondylar femoral fracture model. The experimental group was fixed with screws featuring multilayer Ad-BMP-9/BMSc/GT coatings, while the control groups used medical metal screws and n-CDHA/PAA composite biomaterial screws. Fracture healing was monitored at 1, 4, 12, and 24 weeks, respectively, using X-ray observation, Micro-CT imaging, and SEM. Integration at the material-bone interface and the condition of neo-tissue were assessed through these imaging techniques. RESULTS: The Ad-BMP-9/GT coating significantly enhanced MG63 cell adhesion, proliferation, and differentiation, while increasing BMP-9 expression in vitro. In vivo studies using a rabbit femoral fracture model confirmed the biocompatibility and osteointegration potential of the multilayer Ad-BMP-9/BMSc/GT coated n-CDHA/PAA composite biomaterial screws. Compared to control groups (medical metal screws and n-CDHA/PAA composite biomaterial screws), this material demonstrated faster fracture healing, stronger osteointegration, and facilitated new bone tissue formation with increased calcium deposition at the material-bone interface. CONCLUSION: The multilayer GT-supported BMP-9 coated n-CDHA/PAA composite biomaterials have demonstrated favorable osteogenic cell interface performance, both in vitro and in vivo. This study provides a foundation for developing innovative bone repair materials, holding promise for significant advancements in clinical applications.

Ionic release from bioactive SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) hybrids drives human-bone marrow stromal cell osteogenic differentiation.

This study demonstrates that dissolution products of inorganic/organic SiO2-CaOCME/PTHF/PCL-diCOOH hybrid (70S30CCME-CL) drive human bone marrow stromal cells (h-BMSCs) down an osteogenic pathway with the production of mineralised matrix. We investigated osteogenesis through combined analyses of mRNA dynamics for key markers and targeted staining of mineralised matrix. We demonstrate that h-BMSCs undergo accelerated differentiation in vitro in response to the 70S30CCME-CL ionic milieu, as compared to incubation with osteogenic media. Extracts from 70S30CCME-CL promote osteogenesis by inducing changes in cellular metabolic activity, promoting changes in cell morphology consistent with the osteogenic lineage, and by enhancing mineralisation of hydroxyapatite in the extracellular matrix. Additionally, our results show that 70S30CCME-CL hybrids prove sustained functional resilience by maintaining osteostimulatory effects despite cumulated dissolution cycles. In co-differentiation medium, 70S30CCME-CL ionic release can modulate signalling pathways associated with non-osteogenic functions, further supporting their potential for bone regeneration applications. Overall, our study provides compelling experimental evidence that the 70S30CCME-CL hybrid is a promising biomaterial for bone tissue regeneration applications.

Comparison In Vitro Study on the Interface between Skin and Bone Cell Cultures and Microporous Titanium Samples Manufactured with 3D Printing Technology Versus Sintered Samples.

Percutaneous implants osseointegrated into the residuum of a person with limb amputation need to provide mechanical stability and protection against infections. Although significant progress has been made in the biointegration of percutaneous implants, the problem of forming a reliable natural barrier at the level of the surface of the implant and the skin and bone tissues remains unresolved. The use of a microporous implant structure incorporated into the Skin and Bone Integrated Pylon (SBIP) should address the issue by allowing soft and bone tissues to grow directly into the implant structure itself, which, in turn, should form a reliable barrier to infections and support strong osseointegration. To evaluate biological interactions between dermal fibroblasts and MC3T3-E1 osteoblasts in vitro, small titanium discs (with varying pore sizes and volume fractions to achieve deep porosity) were fabricated via 3D printing and sintering. The cell viability MTT assay demonstrated low cytotoxicity for cells co-cultured in the pores of the 3D-printed and sintered Ti samples during the 14-day follow-up period. A subsequent Quantitative Real-Time Polymerase Chain Reaction (RT-PCR) analysis of the relative gene expression of biomarkers that are associated with cell adhesion (α2, α5, αV, and ß1 integrins) and extracellular matrix components (fibronectin, vitronectin, type I collagen) demonstrated that micropore sizes ranging from 200 to 500 µm of the 3D printed and sintered Ti discs were favorable for dermal fibroblast adhesion. For example, for representative 3D-printed Ti sample S6 at 72 h the values were 4.71 ± 0.08 (α2 integrin), 4.96 ± 0.08 (α5 integrin), 4.71 ± 0.08 (αV integrin), and 1.87 ± 0.12 (ß1 integrin). In contrast, Ti discs with pore sizes ranging from 400 to 800 µm demonstrated the best results (in terms of marker expression related to osteogenic differentiation, including osteopontin, osteonectin, osteocalcin, TGF-ß1, and SMAD4) for MC3T3-E1 cells. For example, for the representative 3D sample S4 on day 14, the marker levels were 11.19 ± 0.77 (osteopontin), 7.15 ± 0.29 (osteonectin), and 6.08 ± 0.12 (osteocalcin), while for sintered samples the levels of markers constituted 5.85 ± 0.4 (osteopontin), 4.45 ± 0.36 (osteonectin), and 4.46 ± 0.3 (osteocalcin). In conclusion, the data obtained show the high biointegrative properties of porous titanium structures, while the ability to implement several pore options in one structure using 3D printing makes it possible to create personalized implants for the best one-time integration with both skin and bone tissues.

Finite element analysis and in vitro tests on endurance life and durability of composite bone substitutes.

Bone structures facilitate the regeneration and repair of bone tissue in regions where it has been damaged or destroyed, either temporarily or permanently. Therefore, the bone's fatigue strength and durability are crucial to its efficacy and longevity. Several variables, such as the construct's material qualities, design, and production procedure, loading and unloading cycles, and physiological conditions influence the endurance life of bone constructs. Metals, ceramics, and polymers are all routinely utilized to create bone substitutes, and each of these materials has unique features that might affect the fatigue strength and endurance life of the final product. The mechanical performance and capacity to promote bone tissue regeneration may be affected by the scaffold's design, porosity, and pore size. Researchers employ mechanical testing under cyclic loading circumstances as one example of an experimental approach used to assess bone construction endurance. These analyses can give us important information about the stress-strain behavior, resistance to multiple loading cycles, and fatigue strength of the new structure. Predicting the endurance life of the developed construct may also be possible with the use of simulations and numerical analyses. Hence, in order to create reliable and efficient constructs for bone tissue engineering, it is crucial to understand their fatigue strength and durability. The purpose of this study is to analyze the effective parameters for fatigue strength of bone structures and to gather the models and evaluations utilized in endurance life assessments.

The biomedical applications of nanozymes in orthopaedics based on regulating reactive oxygen species.

Nanozymes, a category of nanomaterials with enzyme-like activity, have garnered growing interest in various biomedical contexts. Notably, nanozymes that are capable of regulating reactive oxygen species levels by emulating antioxidant or prooxidant enzymes within cells hold significant therapeutic potential for a range of disorders. Herein, we overview the catalytic mechanisms of four exemplary nanozymes within the orthopedic domain. Subsequently, we emphasize recent groundbreaking advancements in nanozyme applications in orthopaedics, encompassing osteoarthritis, osteoporosis, intervertebral disc degeneration, bone defects, spinal cord injury, gout, rheumatoid arthritis, osteosarcoma and bone infection. Furthermore, we discuss the emerging area's future prospects and several noteworthy challenges in biomedical application. This review not only fosters the ongoing development of nanozyme research but also fosters the emergence of more potent nanozymes for the treatment of orthopaedical diseases in the future.

Polycaprolactone Hybrid Scaffold Loaded With N,O-Carboxymethyl Chitosan/Aldehyde Hyaluronic Acid/Hydroxyapatite Hydrogel for Bone Regeneration.

Hydrogels have emerged as potential materials for bone grafting, thanks to their biocompatibility, biodegradation, and flexibility in filling irregular bone defects. In this study, we fabricated a novel NAH hydrogel system, composed of N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronic acid (AHA), and hydroxyapatite (HAp). To improve the mechanical strength of the fabricated hydrogel, a porous polycaprolactone (PCL) matrix was synthesized and used as a three-dimensional (3D) support template for NAH hydrogel loading, forming a novel PCL/NAH hybrid scaffold. A mixture of monosodium glutamate (M) and sucrose (S) at varied weight ratios (5M:5S, 7M:3S, and 9M:1S) was used for the fabrication of 3D PCL matrices. The morphology, interconnectivity, and water resistance of the porous PCL scaffolds were investigated for optimal hydrogel loading efficiency. The results demonstrated that PCL scaffolds with porogen ratios of 7M:3S and 9M:1S possessed better interconnectivity than 5M:5S ratio. The compressive strength of the PCL/NAH hybrid scaffolds with 9M:1S (561.6 ± 6.1 kPa) and 7M:3S (623.8 ± 6.8 kPa) ratios are similar to cancellous bone and all hybrid scaffolds were biocompatible. Rabbit models with tibial defects were implanted with the PCL/NAH scaffolds to assess the wound healing capability. The results suggest that the PCL/NAH hybrid scaffolds, specifically those with porogen ratio of 7M:3S, exhibit promising bone healing effects.

Injectable calcium phosphate cement integrated with BMSCs-encapsulated microcapsules for bone tissue regeneration.

Injectable calcium phosphate cement (CPC) offers significant benefits for the minimally invasive repair of irregular bone defects. However, the main limitations of CPC, including its deficiency in osteogenic properties and insufficient large porosity, require further investigation and resolution. In this study, alginate-chitosan-alginate (ACA) microcapsules were used to encapsulate and deliver rat bone mesenchymal stem cells (rBMSCs) into CPC paste, while a porous CPC scaffold was established to support cell growth. Our results demonstrated that the ACA cell microcapsules effectively protect the cells and facilitate their transport into the CPC paste, thereby enhancing cell viability post-implantation. Additionally, the ACA+CPC extracts were found to stimulate osteogenic differentiation of rBMSCs. Furthermore, results from a rat cranial parietal bone defect model showed that ACA microcapsules containing exogenous rBMSCs initially improved the in situ osteogenic potential of CPC within bone defects, providing multiple sites for bone growth. Over time, the osteogenic potential of the exogenous cells diminishes, yet the pores created by the microcapsules persist in supporting ongoing bone formation by recruiting endogenous cells to the osteogenic sites. In conclusion, the utilization of ACA loaded stem cell microcapsules satisfactorily facilitate osteogenesis and degradation of CPC, making it a promising scaffold for bone defect transplantation.

Synthesis, Characterization and Osteogenic Properties of Chitin-Polydioxanone Composite Gel.

In this study, we have developed a Chitin(Ch)-Poly(dioxanone)(PDO) gel system, which can be potentially used for tissue engineering. Hydrogel has been widely used in biomedical applications for its tuneable properties and biocompatibility. Chitin (Ch) is a natural biopolymer used for its ability to mimic the natural extracellular matrix due to N-acetyl glucosamine structural units. Poly (dioxanone) (PDO) is an FDA-approved synthetic biopolymer known for its mechanical properties, good biocompatibility, and poor inflammatory response. Based on this, we have developed Ch-PDO composite gel using simple regeneration chemistry and characterized it using FT-IR and SEM. The developed composite gel showed improved gel strength, good swelling ability,and controlled degradation behaviour. It also showed good injectability with shear thinning properties and hemocompatibility. Further, the biocompatibility and cell adhesion studies of the prepared gels were studied using dental follicle stem cells (DFSCs). The prepared Ch-PDO gel was biocompatible and showed DFSCs cell attachment. Osteogenic mineralization and RUNX2 expression of the prepared Ch and Ch-PDO gel was studied and Ch-PDO gel showed an enhanced mineralization and RUNX2 expression. Therefore, the developed chitin-PDO gel could be potentially used for bone tissue engineering.

The balance between helper T 17 and regulatory T cells in osteoimmunology and relevant research progress on bone tissue engineering.

BACKGROUND: Bone regeneration is a well-regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process. OBJECTIVE: This review aims to summarize the role of the T-helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering. RESULTS: The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano-structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration. CONCLUSION: Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.

Using hardystonite as a biomaterial in biomedical and bone tissue engineering applications.

Widespread adoption for substitutes of artificial bone grafts based on proper bioceramics has been generated in recent years. Among them, calcium-silicate-based bioceramics, which possess osteoconductive properties and can directly attach to biological organs, have attracted substantial attention for broad ranges of applications in bone tissue engineering. Approaches exist for a novel strategy to promote the drawbacks of bioceramics such as the incorporation of Zn2+, Mg2+, and Zr4+ ions into calcium-silicate networks, and the improvement of their physical, mechanical, and biological properties. Recently, hardystonite (Ca2ZnSi2O7) bioceramics, as one of the most proper calcium-silicate-based bioceramics, has presented excellent biocompatibility, bioactivity, and interaction. Due to its physical, mechanical, and biological behaviors and ability to be shaped utilizing a variety of fabrication techniques, hardystonite possesses the potential to be applied in biomedical and tissue engineering, mainly bone tissue engineering. A notable potential exists for the newly developed bioceramics to help therapies supply clinical outputs. The promising review paper has been presented by considering major aims to summarize and discuss the most applicable studies carried out for its physical, mechanical, and biological behaviors.

Osteogenic potentials in canine mesenchymal stem cells: unraveling the efficacy of polycaprolactone/hydroxyapatite scaffolds in veterinary bone regeneration.

BACKGROUND: The integration of stem cells, signaling molecules, and biomaterial scaffolds is fundamental for the successful engineering of functional bone tissue. Currently, the development of composite scaffolds has emerged as an attractive approach to meet the criteria of ideal scaffolds utilized in bone tissue engineering (BTE) for facilitating bone regeneration in bone defects. Recently, the incorporation of polycaprolactone (PCL) with hydroxyapatite (HA) has been developed as one of the suitable substitutes for BTE applications owing to their promising osteogenic properties. In this study, a three-dimensional (3D) scaffold composed of PCL integrated with HA (PCL/HA) was prepared and assessed for its ability to support osteogenesis in vitro. Furthermore, this scaffold was evaluated explicitly for its efficacy in promoting the proliferation and osteogenic differentiation of canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) to fill the knowledge gap regarding the use of composite scaffolds for BTE in the veterinary orthopedics field. RESULTS: Our findings indicate that the PCL/HA scaffolds substantially supported the proliferation of cBM-MSCs. Notably, the group subjected to osteogenic induction exhibited a markedly upregulated expression of the osteogenic gene osterix (OSX) compared to the control group. Additionally, the construction of 3D scaffold constructs with differentiated cells and an extracellular matrix (ECM) was successfully imaged using scanning electron microscopy. Elemental analysis using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy confirmed that these constructs possessed the mineral content of bone-like compositions, particularly the presence of calcium and phosphorus. CONCLUSIONS: This research highlights the synergistic potential of PCL/HA scaffolds in concert with cBM-MSCs, presenting a multidisciplinary approach to scaffold fabrication that effectively regulates cell proliferation and osteogenic differentiation. Future in vivo studies focusing on the repair and regeneration of bone defects are warranted to further explore the regenerative capacity of these constructs, with the ultimate goal of assessing their potential in veterinary clinical applications.

Composite bioink incorporating cell-laden liver decellularized extracellular matrix for bioprinting of scaffolds for bone tissue engineering.

The field of bone tissue engineering (BTE) has witnessed a revolutionary breakthrough with the advent of three-dimensional (3D) bioprinting technology, which is considered an ideal choice for constructing scaffolds for bone regeneration. The key to realizing scaffold biofunctions is the selection and design of an appropriate bioink, and existing bioinks have significant limitations. In this study, a composite bioink based on natural polymers (gelatin and alginate) and liver decellularized extracellular matrix (LdECM) was developed and used to fabricate scaffolds for BTE using 3D bioprinting. Through in vitro studies, the concentration of LdECM incorporated into the bioink was optimized to achieve printability and stability and to improve the proliferation and osteogenic differentiation of loaded rat bone mesenchymal stem cells (rBMSCs). Furthermore, in vivo experiments were conducted using a Sprague Dawley rat model of critical-sized calvarial defects. The proposed rBMSC-laden LdECM-gelatin-alginate scaffold, bioprinted layer-by-layer, was implanted in the rat calvarial defect and the development of new bone growth was studied for four weeks. The findings showed that the proposed bioactive scaffolds facilitated angiogenesis and osteogenesis at the defect site. The findings of this study suggest that the developed rBMSC-laden LdECM-gelatin-alginate bioink has great potential for clinical translation and application in solving bone regeneration problems.