Incorporation of carboxymethyl chitosan (CMCS) for the modulation of physio-chemical characteristics and cell proliferation environment of the composite hydrogel microspheres.

Hydrogels have excellent swelling properties and have been widely applied in tissue engineering because of their similarity to the extracellular matrix (ECM). Sodium alginate (SA) and carboxymethyl chitosan (CMCS) were prepared into hydrogel microspheres with Ca2+crosslinking in our study. The morphology, inner structure, mechanical properties, water content, swelling rate and BMP-2 loading and releasing properties were characterized. Our results showed that the composite SA /CMCS hydrogel microspheres were translucent and spherical in shape with uniform particle size. The incorporation of CMCS further increased the diameters of the microspheres, internal pore structure, water content, and mechanical properties of the SA/CMCS hydrogel microspheres. At the same SA concentration, with the increase of CMSC concentration, the diameter of microspheres could be increased by about 0.4 mm, the water content can be increased about 1%-2%. As for the mechanical properties, the compressive strength can be increased by 0.04-0.1 MPa, and the modulus of elasticity can be increased by 0.1-0.15 MPa. BMP-2 was chosen as a model agent and it could be loaded into SA/CMCS microspheres, and the incorporation of CMCS increased BMP-2 loading. The encapsulated BMP-2 was sustainably releasedin vitro. The leaching solutions of the SA/CMCS hydrogel microspheres exhibited good cytocompatibility and could increase ALP activity, ALP expression, and biomineralization on MC3T3-E1 cells. After 7 d of co-culture, ALP activities in S2.5C2 and S2.5C3 groups was increased by 50% and 45% compared with that of the control group. When embedded in the SA/CMCS microspheres, the MC3T3-E1 cells were evenly distributed inside the hydrogel microspheres and remained viable. Transcriptomic studies showed that incorporation of CMCS induced upregulation of 1141 differentially expressed genes (DEGs) and downregulation of 1614 DEGs compared with SA microspheres. The most significantly enriched pathways were the Wnt and MAPK signaling pathways induced by the incorporation of CMCS and BMP-2. In conclusion, our results indicated that the physiochemical characteristics of the SA hydrogel microspheres could be greatly modulated by CMCS to better mimic the ECM microenvironment and induce osteo-inductive activities of MC3T3-E1 cells.

Photothermal Antibacterial and Osteoinductive Polypyrrole@Cu Implants for Biological Tissue Replacement.

The treatment of bone defects caused by disease or accidents through the use of implants presents significant clinical challenges. After clinical implantation, these materials attract and accumulate bacteria and hinder the integration of the implant with bone tissue due to the lack of osteoinductive properties, both of which can cause postoperative infection and even lead to the eventual failure of the operation. This work successfully prepared a novel biomaterial coating with multiple antibacterial mechanisms for potent and durable and osteoinductive biological tissue replacement by pulsed PED (electrochemical deposition). By effectively regulating PPy (polypyrrole), the uniform composite coating achieved sound physiological stability. Furthermore, the photothermal analysis showcased exceptional potent photothermal antibacterial activity. The antibacterial assessments revealed a bacterial eradication rate of 100% for the PPy@Cu/PD composite coating following a 24 h incubation. Upon the introduction of NIR (near-infrared) irradiation, the combined effects of multiple antibacterial mechanisms led to bacterial reduction rates of 99% for E. coli and 98% for S. aureus after a 6 h incubation. Additionally, the successful promotion of osteoblast proliferation was confirmed through the application of the osteoinductive drug PD (pamidronate disodium) on the composite coating's surface. Therefore, the antimicrobial Ti-based coatings with osteoinductive properties and potent and durable antibacterial properties could serve as ideal bone implants.

Multifunctional Bone Regeneration Membrane with Flexibility, Electrical Stimulation Activity and Osteoinductive Activity.

The use of membrane-based guided bone regeneration techniques has great potential for single-stage reconstruction of critical-sized bone defects. Here, a multifunctional bone regeneration membrane combining flexible elasticity, electrical stimulation (ES) and osteoinductive activity is developed by in situ doping of MXene 2D nanomaterials with conductive functionality and ß-TCP particles into a Poly(lactic acid-carbonate (PDT) composite nano-absorbable membrane (P/T/MXene) via electrostatic spinning technique. The composite membrane has good feasibility due to its temperature sensitivity, elastic memory capacity, coordinated degradation profile and easy preparation process. In vitro experiments showed the P/T/MXene membrane effectively promoted the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under ES and enhanced the angiogenic capacity of endothelial cells, which synergistically promoted bone regeneration through neovascularization. In addition, an in vivo rat model of cranial bone defects further confirmed the bone regeneration efficacy of the P/T/MXene membrane. In conclusion, the developed P/T/MXene membrane can effectively promote bone regeneration through their synergistic multifunctional effects, suggesting the membranes have great potential for guiding tissue regeneration and providing guidance for the biomaterials design.

A functional analysis of a resorbable citrate-based composite tendon anchor.

Rapid and efficient tendon fixation to a bone following trauma or in response to degenerative processes can be facilitated using a tendon anchoring device. Osteomimetic biomaterials, and in particular, bio-resorbable polymer composites designed to match the mineral phase content of native bone, have been shown to exhibit osteoinductive and osteoconductive properties in vivo and have been used in bone fixation for the past 2 decades. In this study, a resorbable, bioactive, and mechanically robust citrate-based composite formulated from poly(octamethylene citrate) (POC) and hydroxyapatite (HA) (POC-HA) was investigated as a potential tendon-fixation biomaterial. In vitro analysis with human Mesenchymal Stem Cells (hMSCs) indicated that POC-HA composite materials supported cell adhesion, growth, and proliferation and increased calcium deposition, alkaline phosphatase production, the expression of osteogenic specific genes, and activation of canonical pathways leading to osteoinduction and osteoconduction. Further, in vivo evaluation of a POC-HA tendon fixation device in a sheep metaphyseal model indicates the regenerative and remodeling potential of this citrate-based composite material. Together, this study presents a comprehensive in vitro and in vivo analysis of the functional response to a citrate-derived composite tendon anchor and indicates that citrate-based HA composites offer improved mechanical and osteogenic properties relative to commonly used resorbable tendon anchor devices formulated from poly(L-co-D, l-lactic acid) and tricalcium phosphate PLDLA-TCP.

Osteoinductive Properties of Autologous Dentin: An Ex Vivo Study on Extracted Teeth.

Over the last decades, a variety of biomaterials, ranging from synthetic products to autologous and heterologous grafts, have been recommended to conserve and regenerate bone tissue after tooth extraction. We conducted a biochemical study on ground extracted teeth that aimed to evaluate the osteoinductive and osteoconductive potential of dentin by assessing the releases of bone morphogenetic protein (BMP-2), osteocalcin (OC) and osteonectin (ON) over time (24 h, 10 days and 28 days). Twenty-six patients, who required the extraction of nonrestorable teeth, were enrolled in the study according to the inclusion criteria, as follows: thirteen young patients 18 to 49 years of age (UNDER 50), and thirteen patients of 50 to 70 years (OVER 50); a total of twenty-six teeth were extracted, ground and analyzed by enzyme-linked immunosorbent assays (ELISA). All ground teeth released BMP-2, OC and ON at each time point; no differences were observed between the UNDER-50 and OVER-50 patients. The results of the study support the use of autologous dentin as osteoinductive material for bone regeneration procedures, irrespective of patients' ages.

Osteoinductive and regenerative potential of premixed calcium-silicate bioceramic sealers on vascular wall mesenchymal stem cells.

AIM: The osteogenic potential of new premixed calcium-silicate-containing bioceramic sealers (Ca-Si sealers) was tested with porcine vascular wall-mesenchymal stem cells (pVW-MSCs). METHODOLOGY: Two Ca-Si-containing sealers: Ceraseal (MetaBiomed, Cheong-si, South Korea) and AH Plus Bioceramic (Maruchi, Wonju-si, South Korea), and an epoxy resin sealer (AH Plus; Dentsply, Konstanz, Germany) as a control, were prepared according to the manufacturers' indications. All samples were allowed to set for 100% of their setting time in a sterile humid cabinet at 37°C and 95% relative humidity. pVW-MSC seeding efficiency and osteogenic differentiation were analysed as marker of gene/protein expression for up to 12 days. Mineralization assay and immunofluorescence staining were performed and evaluated over a period of 21 days. Statistical analyses were conducted using one-way analysis of variance (p < .05). Additional samples were prepared and stored under the same conditions and inspected using an environmental scanning electron microscope equipped with an energy dispersive X-ray spectroscopy system. RESULTS: Significantly higher cell seeding efficiency (p < .05) was observed for both Ca-Si sealers from day 8. pVW-MSCs showed a significant shift towards the osteogenic lineage only when seeded in contact with Ca-Si sealers. Gene expression of osteopontin was upregulated significantly. Collagen I and osteocalcin were clearly expressed by cells in contact with Ca-Si sealers. Mineralization granules were observed in Alizarin red assays and confocal laser scanning microscopy analysis of both Ca-Si sealers. No gene expression or granule mineralization were observed on the epoxy resin sealer. CONCLUSIONS: Premixed Ca-Si sealers displayed a higher potential for osteogenic activity on pVW-MSCs. Epoxy resin sealer was unable to induce any osteogenic activity. The properties of both Ca-Si sealers suggest their potential as osteoinductive platforms for vascular MSCs in periapical bone.

Calcium phosphate graphene and Ti3C2Tx MXene scaffolds with osteogenic and antibacterial properties.

Bioactive degradable scaffolds that facilitate bone healing while fighting off initial bacterial infection have the potential to change established strategies of dealing with traumatic bone injuries. To achieve this a composite material made from calcium phosphate graphene (CaPG), and MXene was synthesized. CaPG was created by functionalizing graphene oxide with phosphate groups in the presence of CaBr with a Lewis acid catalyst. Through this transformation, Ca2+ and PO4 3- inducerons are released as the material degrades thereby aiding in the process of osteogenesis. The 2D MXene sheets, which have shown to have antibacterial properties, were made by etching the Al from a layered Ti3AlC2 (MAX phase) using HF. The hot-pressed scaffolds made of these materials were designed to combat the possibility of infection during initial surgery and failure of osteogenesis to occur. These two failure modes account for a large percentage of issues that can arise during the treatment of traumatic bone injuries. These scaffolds were able to retain induceron-eluting properties in various weight percentages and bring about osteogenesis with CaPG alone and 2 wt% MXene scaffolds demonstrating increased osteogenic activity as compared to no treatment. Additionally, added MXene provided antibacterial properties that could be seen at as little as 2 wt%. This CaPG and MXene composite provides a possible avenue for developing osteogenic, antibacterial materials for treating bone injuries.

An Innovative Design to Enhance Osteoinductive Efficacy and Biomechanical Behavior of a Titanium Dental Implant.

The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine-premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.

Additive Manufacturing of Wet-Spun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-Based Scaffolds Loaded with Hydroxyapatite.

Tissue engineering represents an advanced therapeutic approach for the treatment of bone tissue defects. Polyhydroxyalkanoates are a promising class of natural polymers in this context thanks to their biocompatibility, processing versatility, and mechanical properties. The aim of this study is the development by computer-aided wet-spinning of novel poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)-based composite scaffolds for bone engineering. In particular, PHBV scaffolds are loaded with hydroxyapatite (HA), an osteoinductive ceramic, in order to tailor their biological activity and mechanical properties. PHBV blending with poly(lactide-co-glycolide) (PLGA) is also explored to increase the processing properties of the polymeric mixture used for composite scaffold fabrication. Different HA percentages, up to 15% wt., can be loaded into the PHBV or PHBV/PLGA scaffolds without compromising their interconnected porous architecture, as well as the polymer morphological and thermal properties, as demonstrated by scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. In addition, HA loading results in increased scaffold compressive stiffness to levels comparable to those of trabecular bone tissue, as well as in higher in vitro MC3T3-E1 cell viability and production of mineralized extracellular matrix, in comparison to what observed for unloaded scaffolds. The observed mechanical and biological properties suggest the suitability of the developed scaffolds for bone engineering.

Polyhydroxybutyrate-based osteoinductive mineralized electrospun structures that mimic components and tissue interfaces of the osteon for bone tissue engineering.

Scaffolds for bone tissue engineering should enable regeneration of bone tissues with its native hierarchically organized extracellular matrix (ECM) and multiple tissue interfaces. To achieve this, inspired by the structure and properties of bone osteon, we fabricated polyhydroxybutyrate (PHB)-based mineralized electrospun fibrous scaffolds. After studying multiple PHB-based fibers, we chose 7%PHB/1%Gelatin fibers (PG) to fabricate mineralized fibers that mimic mineralized collagen fibers in bone. The mineralized PG (mPG) surface had a rough, hydrophilic layer of low crystalline calcium phosphate which was biocompatible to bone marrow stromal cells (BMSCs), induced their proliferation and was osteoinductive. Subsequently, by modulating the electrospinning process, we fabricated mPG-based novel higher order fibrous scaffolds that mimic the macroscale geometries of osteons of bone ECM. Inspired by the aligned collagen fibers in bone lamellae, we fabricated mPG scaffolds with aligned fibers that could direct anisotropic elongation of mouse BMSC (mBMSCs). Further, we fabricated electrospun mPG-based osteoinductive tubular constructs which can mimic cylindrical bone components like osteons or lamellae or be used as long bone analogues based on their dimensions. Finally, to regenerate tissue interfaces in bone, we introduced a novel bi-layered scaffold-based approach. An electrospun bi-layered tubular construct that had PG in the outer layer and 7%PHB/0.5%Polypyrrole fibers (PPy) in the inner layer was fabricated. The bi-layered tubular construct underwent preferential surface mineralization only on its outer layer. This outer mineralized layer supported osteogenesis while the inner PPy layer could support neural cell growth. Thus, the bi-layered tubular construct may be used to regenerate haversian canal in the osteons which hosts nerve fibers. Overall, the study introduced novel techniques to fabricate biomimetic structures that can regenerate components of bone osteon and its multiple tissue interfaces. The study lays foundation for the fabrication of a modular scaffold that can regenerate bone with its hierarchical structure and complex tissue interfaces.

Demineralized dentin matrix for bone regeneration in dentistry: A critical update.

Over the last few decades, several new materials and techniques have been developed for bone regeneration. Scaffolds based on demineralized dentin matrix (DDM) present an attractive option due to their availability and several animal and human studies have been conducted to ascertain their utility in regenerative dentistry. The aim of this review was to summarize the recent studies conducted on DDM and used for bone grafts. PubMed, Web of Science, and Scopus were used to search for studies published within the last 10 years. The keywords and terms used were: "demineralized dentine matrix", "bone grafting", "bone augmentation" and "guided tissue regeneration" in various combinations. Original studies (in vitro, animal and human) and systematic reviews were included in the literature search. The literature search initially identified 23 studies (16 animal studies and 7 clinical reports. Most studies included in this review indicate that DDM has demonstrated promising results in a variety of dental and regenerative medicine applications. Further studies are required to completely comprehend its characteristics and prospective applications. Future studies should also focus on optimizing the processing protocols for the production of DDM-based scaffolds.

Conducting biointerface of spider-net-like chitosan-adorned polyurethane/SPIONs@SrO2-fMWCNTs for bone tissue engineering and antibacterial efficacy.

In pursuit of enhancing bone cell proliferation, this study delves into the fabrication of porous scaffolds through the integration of nanomaterials. Specifically, we present the development of highly conductive chitosan (CS) nanonets on fibro-porous polyurethane (PU) bio-membranes. These nanofibers comprise functionalized multiwall carbon nanotubes (fMWCNTs), well-dispersed superparamagnetic iron oxide (SPIONs), and strontium oxide (SrO2) nanoparticles. The resulting porous scaffold exhibits remarkable interfacial biocompatibility, antibacterial properties, and load-bearing capability. Through meticulous in vitro investigations, the CS-PU/SPIONs/SrO2-fMWCNTs nanofibrous scaffolds have demonstrated a propensity to promote bone cell regeneration. Notably, the integration of these nanomaterials has been found to upregulate crucial bone-related markers, including ALP, ARS, COL-I, RUNX2, and SPP-I. The evaluation of these markers, conducted through quantitative real-time polymerase chain reaction (qRT-PCR) and immunocytochemistry, substantiates the improved cell survival and enhanced osteogenic differentiation facilitated by the integrated nanomaterials. This comprehensive analysis underscores the efficacy of CS-PU/SPIONs/SrO2-fMWCNTs bioscaffolds in promoting MC3T3-E1 cell regeneration within, thereby holding promise for advancements in bone tissue engineering and regenerative medicine.

Bone Tissue Engineering Scaffolds: Materials and Methods.

The wide development in biomedical, regenerative medicine, and surgical techniques has ensured that new technologies are developed to improve patient-specific treatment and care. Tissue engineering is a special field in biomedical engineering that works toward cell development using scaffolds. Bone tissue engineering is a separate branch of tissue engineering, in which the construction of bone, functionalities of bone, and bone tissue regeneration are studied in detail to repair or regenerate new functional bone tissues. In India alone, people suffering from bone diseases are extensive in numbers. Almost 15% to 20% of the population suffers from osteoporosis. Bone scaffolds are proving to be an excellent solution for osseous abnormalities or defect treatment. Scaffolds are three dimensional (3D) and mostly porous structures created to enhance new tissue growth. Bone scaffolds are specially designed to promote osteoinductive cell growth, expansion, and migration on their surface. This review article aims to provide an overview of possible bone scaffolding materials in practice, different 3D techniques to fabricate these scaffolds, and effective bone scaffold characteristics targeted by researchers to fabricate tissue-engineered bone scaffolds.

Allogenic Bone Graft in Dentistry: A Review of Current Trends and Developments.

In an effort to prepare non-autologous bone graft or biomaterial that would possess characteristics comparable to autologous bone, many different allogenic bone derivatives have been created. Although different existing processing methods aim to achieve the very same results, the specific parameters applied during different stages material preparation can result in significant differences in the material's mechanical and biological properties The properties, including osteoconductive, osteoinductive, and even osteogenic potential, can differ vastly depending on particular preparation and storage techniques used. Osteogenic properties, which have long been thought to be characteristic to autogenic bone grafts only, now seem to also be achievable in allogenic materials due to the possibility to seed the host's stem cells on a graft before its implantation. In this article, we aim to review the available literature on allogenic bone and its derivatives as well as the influence of different preparation methods on its performance.

Multipotent Mesenchymal Cells Homing and Differentiation on Poly(ε-caprolactone) Blended with 20% Tricalcium Phosphate and Polylactic Acid Incorporating 10% Hydroxyapatite 3D-Printed Scaffolds via a Commercial Fused Deposition Modeling 3D Device.

As highlighted by the 'Global Burden of Disease Study 2019' conducted by the World Health Organization, ensuring fair access to medical care through affordable and targeted treatments remains crucial for an ethical global healthcare system. Given the escalating demand for advanced and urgently needed solutions in regenerative bone procedures, the critical role of biopolymers emerges as a paramount necessity, offering a groundbreaking avenue to address pressing medical needs and revolutionize the landscape of bone regeneration therapies. Polymers emerge as excellent solutions due to their versatility, making them reliable materials for 3D printing. The development and widespread adoption of this technology would impact production costs and enhance access to related healthcare services. For instance, in dentistry, the use of commercial polymers blended with ß-tricalcium phosphate (TCP) is driven by the need to print a standardized product with osteoconductive features. However, modernization is required to bridge the gap between biomaterial innovation and the ability to print them through commercial printing devices. Here we showed, for the first time, the metabolic behavior and the lineage commitment of bone marrow-derived multipotent mesenchymal cells (MSCs) on the 3D-printed substrates poly(e-caprolactone) combined with 20% tricalcium phosphate (PCL + 20% ß-TCP) and L-polylactic acid (PLLA) combined with 10% hydroxyapatite (PLLA + 10% HA). Although there are limitations in printing additive-enriched polymers with a predictable and short half-life, the tested 3D-printed biomaterials were highly efficient in supporting osteoinductivity. Indeed, considering different temporal sequences, both 3D-printed biomaterials resulted as optimal scaffolds for MSCs' commitment toward mature bone cells. Of interest, PLLA + 10% HA substrates hold the confirmation as the finest material for osteoinduction of MSCs.

The genetic background determines material-induced bone formation through the macrophage-osteoclast axis.

Osteoinductive materials are characterized by their ability to induce bone formation in ectopic sites. Thus, osteoinductive materials hold promising potential for repairing bone defects. However, the mechanism of material-induced bone formation remains unknown, which limits the design of highly potent osteoinductive materials. Here, we demonstrated a genetic background link among macrophage polarization, osteoclastogenesis and material-induced bone formation. The intramuscular implantation of an osteoinductive material in FVB/NCrl (FVB) mice resulted in more M2 macrophages at week 1, more osteoclasts at week 2 and increased bone formation after week 4 compared with the results obtained in C57BL/6JOlaHsd (C57) mice. Similarly, in vitro, with a greater potential to form M2 macrophages, monocytes derived from FVB mice formed more osteoclasts than those derived from C57 mice. A transcriptomic analysis identified Csf1, Cxcr4 and Tgfbr2 as the main genes controlling macrophage-osteoclast coupling, which were further confirmed by related inhibitors. With such coupling, macrophage polarization and osteoclast formation of monocytes in vitro successfully predicted in vivo bone formation in four other mouse strains. Considering material-induced bone formation as an example of acquired heterotopic bone formation, the current findings shed a light on precision medicine for both bone regeneration and the treatment of pathological heterotopic bone formation.

Osteoinduction and osteoimmunology: Emerging concepts.

The recognition and importance of immune cells during bone regeneration, including around bone biomaterials, has led to the development of an entire field termed "osteoimmunology," which focuses on the connection and interplay between the skeletal system and immune cells. Most studies have focused on the "osteogenic" capacity of various types of bone biomaterials, and much less focus has been placed on immune cells despite being the first cell type in contact with implantable devices. Thus, the amount of literature generated to date on this topic makes it challenging to extract needed information. This review article serves as a guide highlighting advancements made in the field of osteoimmunology emphasizing the role of the osteoimmunomodulatory properties of biomaterials and their impact on osteoinduction. First, the various immune cell types involved in bone biomaterial integration are discussed, including the prominent role of osteal macrophages (OsteoMacs) during bone regeneration. Thereafter, key biomaterial properties, including topography, wettability, surface charge, and adsorption of cytokines, growth factors, ions, and other bioactive molecules, are discussed in terms of their impact on immune responses. These findings highlight and recognize the importance of the immune system and osteoimmunology, leading to a shift in the traditional models used to understand and evaluate biomaterials for bone regeneration.

Cell seeding via bioprinted hydrogels supports cell migration into porous apatite-wollastonite bioceramic scaffolds for bone tissue engineering.

Cell seeding via cell-laden hydrogels offers a rapid way of depositing cells onto a substrate or scaffold. When appropriately formulated, hydrogels provide a dense network of fibres for cellular encapsulation and attachment, creating a protective environment that prevents cells to be washed away by media. However, when incorporating hydrogels into a cell seeding strategy the cellular capacity for migration from a hydrogel network and subsequent biofunctionality must be assessed. Here, we compare cell seeding via a bioprinted hydrogel with conventional manual cell seeding in media. To this end, we use a binder jet 3D printed bioceramic scaffold as a model system for bone tissue engineering and the reactive jet impingement (ReJI) bioprinting system to deliver high cell density cell-laden hydrogels onto the surface of the scaffolds. The bioceramic scaffolds were produced in apatite-wollastonite (AW) glass-ceramic, with a total porosity of ~50 %, with pore size predominantly around 50-200 µm. Bone marrow-derived mesenchymal stromal cells were seeded onto the porous AW substrate both in media and via ReJI bioprinting. Cell seeding in media confirmed the osteoinductive nature and the ability of the scaffold to support cell migration within the porous structure. Cell seeding via ReJI bioprinting demonstrated that the cell-laden hydrogel penetrated the porous AW structure upon hydrogel deposition. Furthermore, cells would then migrate out from the hydrogel network and interact with the bioceramic substrate. Overall, levels of cell migration and mineralisation were significant and comparable for both seeding approaches. However, cell seeding via bioprinted hydrogels may serve as an effective strategy for in situ cell seeding into implants, which is desired in clinical tissue engineering procedures, avoiding the time taken for cell attachment from media, and the requirement to maintain a specific orientation until attachment has occurred.

Potential application of inorganic nano-materials in modulation of macrophage function: Possible application in bone tissue engineering.

Nanomaterials indicate unique physicochemical properties for drug delivery in osteogenesis. Benefiting from high surface area grades, high volume ratio, ease of functionalization by biological targeting moieties, and small size empower nanomaterials to pass through biological barriers for efficient targeting. Inorganic nanomaterials for bone regeneration include inorganic synthetic polymers, ceramic nanoparticles, metallic nanoparticles, and magnetic nanoparticles. These nanoparticles can effectively modulate macrophage polarization and function, as one of the leading players in osteogenesis. Bone healing procedures in close cooperation with the immune system. Inflammation is one of the leading triggers of the bone fracture healing barrier. Macrophages commence anti-inflammatory signaling along with revascularization in the damaged site to promote the formation of a soft callus, bone mineralization, and bone remodeling. In this review, we will discuss the role of macrophages in bone hemostasis and regeneration. Furthermore, we will summarize the influence of the various inorganic nanoparticles on macrophage polarization and function in the benefit of osteogenesis.

Hemostatic Collagen Sponge with High Porosity Promotes the Proliferation and Adhesion of Fibroblasts and Osteoblasts.

The use of biomaterial for tissue repair involves the interaction between materials and cells, and the coagulum formation represents the first step of tissue healing. This process is particularly critical in the oral cavity, where the wounds are immediately subjected to the masticatory mechanical stress, saliva invasion, and bacterial attack. Therefore, the present study aimed to explore the structural features and the biological activities of a hemostatic collagen sponge on human gingival fibroblasts (HGFs) and human oral osteoblasts (HOBs). The microstructure of the collagen sponge was characterized by a scanning electron microscope (SEM) and histological analysis. The porosity was also calculated. To investigate biological activities, HGFs and HOBs were cultured on the collagen sponges, and their adhesion was observed at SEM on the third day, while cell viability was investigated at the third and seventh days by Tetrazolium (MTT) assay. For osteoblasts seeded on collagen sponge the mineralization ability was also evaluated by alkaline phosphatase (ALP) assay at the seventh day, and by Alizarin red staining on the 14th. Furthermore, the gene expression of ALP and osteocalcin (OCN) was investigated after 3, 7 and 14 days. SEM images of the sponge without cells showed a highly porous 3D structure, confirmed by the measurement of porosity that was more than 90%. The samples cultured were characterized by cells uniformly distributed and adhered to the sponge surface. Proliferation ended up being promoted, as well as the mineralization ability of the osteoblasts, mainly at the mature stage. In conclusion, this collagen sponge could have a potential use for tissue healing.