Bone Tissue Regeneration Research Articles

Bioactive ceramic-based materials: beneficial properties and potential applications in dental repair and regeneration.

Bioactive ceramics, primarily consisting of bioactive glasses, glass-ceramics, calcium orthophosphate ceramics, calcium silicate ceramics and calcium carbonate ceramics, have received great attention in the past decades given their biocompatible nature and excellent bioactivity in stimulating cell proliferation, differentiation and tissue regeneration. Recent studies have tried to combine bioactive ceramics with bioactive ions, polymers, bioactive proteins and other chemicals to improve their mechanical and biological properties, thus rendering them more valid in tissue engineering scaffolds. This review presents the beneficial properties and potential applications of bioactive ceramic-based materials in dentistry, particularly in the repair and regeneration of dental hard tissue, pulp-dentin complex, periodontal tissue and bone tissue. Moreover, greater insights into the mechanisms of bioactive ceramics and the development of ceramic-based materials are provided.

Montmorillonite-reinforced xanthan gum-based biomaterial enhances biomineralization suitable for bone tissue engineering

In the present study, we effectively constructed a biomaterial that consists of Xanthan gum, DEGDMA and montmorillonite infused as nanofillers for their prospective application in the restoration of bone. Utilizing FTIR, XRD, TGA, SEM, and numerous other techniques, each of the physicochemical features related to the synthesized biomaterial was characterized. The incorporation of montmorillonite was found to induce noticeable rheological characteristics. The fabricated biomaterial shows a more controlled release of drugs. The biocompatibility and the cytocompatibility of the synthesized biomaterial were demonstrated by the cellular attachment and growth of different secondary cell lines which remain active but do not produce enhanced ROS. An elevated ALP-activity, improved differentiation and increased mineralization by SaOS-2 cells on the developed biomaterial under an osteoinductive environment impart its capability for osteogenesis. This material can be used for delivering drugs and can serve as an affordable substrate for cellular activity. We claim that this material possesses the features suitable for bone tissue regeneration and restoration. We propose that the developed biomaterial has future implications in the biomedical sector at low cost.

ПРОЦЕССЫ РЕГЕНЕРАЦИИ КОСТНОЙ ТКАНИ ПРИ ПЕРЕЛОМАХ НИЖНЕЙ ЧЕЛЮСТИ

Item. The review of literature devoted to the actual problem of maxillofacial surgery — processes of bone tissue regeneration in mandibular fractures is presented. The purpose of the study — to study and analyze the materials of publications on the processes of bone tissue regeneration in mandibular fractures. Methodology. The publications of domestic and foreign authors devoted to the processes of bone tissue regeneration in mandibular fractures were studied. The publications were analyzed using scientific search library databases: PubMed Central, Google, Cyberleninka, eLibrary. Materials were selected by keywords. Full-text articles were included in the search. Results. In domestic and foreign literature, the processes of restoration of bone structures of the maxillofacial region as an organism's response to damage have been studied and described in detail. It has been established that two processes are simultaneously launched: resorption of damaged osteocytes and formation of osteoid tissue, one of which may be predominant at the moment. Conclusions. The article presents modern data on the key moments of bone tissue regeneration in the region of the mandible. All stages of the reparative process in bone tissue are described at the cellular level, and information about the main mechanisms, pathways and cell types involved in bone tissue regeneration is presented in detail, taking into account the stage of osteogenesis. Knowledge of the regularities of biological processes in the bone tissue regeneration zone allows scientific search and development of effective methods of treatment of mandibular fractures.

Skeletal stem and progenitor cells in bone development and repair.

Bone development, growth, and repair are complex processes involving various cell types and interactions, with central roles played by skeletal stem and progenitor cells. Recent research brought new insights into the skeletal precursor populations that mediate intramembranous and endochondral bone development. Later in life, many of the cellular and molecular mechanisms determining development are reactivated upon fracture, with powerful trauma-induced signaling cues triggering a variety of postnatal skeletal stem/progenitor cells (SSPCs) residing near the bone defect. Interestingly, in this injury context, the current evidence suggests that the fates of both SSPCs and differentiated skeletal cells can be considerably flexible and dynamic, and that multiple cell sources can be activated to operate as functional progenitors generating chondrocytes and/or osteoblasts. The combined implementation of in vivo lineage tracing, cell surface marker-based cell selection, single-cell molecular analyses, and high-resolution in situ imaging has strongly improved our insights into the diversity and roles of developmental and reparative stem/progenitor subsets, while also unveiling the complexity of their dynamics, hierarchies, and relationships. Albeit incompletely understood at present, findings supporting lineage flexibility and possibly plasticity among sources of osteogenic cells challenge the classical dogma of a single primitive, self-renewing, multipotent stem cell driving bone tissue formation and regeneration from the apex of a hierarchical and strictly unidirectional differentiation tree. We here review the state of the field and the newest discoveries in the origin, identity, and fates of skeletal progenitor cells during bone development and growth, discuss the contributions of adult SSPC populations to fracture repair, and reflect on the dynamism and relationships among skeletal precursors and differentiated cell lineages. Further research directed at unraveling the heterogeneity and capacities of SSPCs, as well as the regulatory cues determining their fate and functioning, will offer vital new options for clinical translation toward compromised fracture healing and bone regenerative medicine.

A study on antibacterial and anti‐inflammatory activity of xylitol‐based polymeric nano‐bioactive glass nanocomposites

AbstractBioactive glasses have been shown effective in promoting bone healing by interacting with the body, gradual degradation, and supporting new bone growth. They present a promising option for therapies aimed at regenerating bone tissue. In this study, we developed a novel material, PXMA/n‐BG, by combining xylitol, maleic acid, and adipic acid, and incorporating nano‐bioactive glass, all synthesized without the use of a catalyst. The sol–gel method was used to fabricate the n‐BG (SiO2–CaO–P2O5). The incorporation of n‐BG into the polymer was found to enhance its biocompatibility and effectiveness for orthopedic applications. The synthesized polymer and its nanocomposite were characterized by FTIR, 1H NMR, 13C NMR, DSC, GPC, UTM, XRD and HR‐SEM. X‐ray diffraction and high‐resolution scanning electron microscopy are utilized to investigate the structure and surface of the n‐BG and polymeric composite material. The strength and flexibility of a plastic material with tiny particles mixed in were tested using a universal testing machine. We examined the elemental composition and thermal stability of n‐BG through specialized testing like energy‐dispersive X‐ray analysis (EDX) and thermogravimetric analysis (TGA). The research focused on the potential of xylitol‐based polymer and its nanocomposite to inhibit the growth of harmful bacteria in food. We conducted experiments to determine the efficacy of the antibacterial substance against various bacteria strains. The antibacterial potential of the extracts was assessed by the agar diffusion method using MHA plate. Furthermore, we investigated the ability of the material and its nanoparticles to reduce inflammation.

Enhancing calvarial defects repair with PDGF-BB mimetic peptide hydrogels

Addressing bone defects represents a significant challenge to public health. Localized delivery of growth factor has emerged as promising approach for bone regeneration. However, the clinical application of Platelet-Derived Growth Factor (PDGF) is hindered by its high cost and short half-life. In this work, we introduce the application of PDGF-mimicking peptide (PMP1) hydrogels for calvarial defect restoration, showcasing their remarkable effectiveness. Through osteogenic differentiation assays and q-PCR analyses, we demonstrate PMP1's substantial capacity to enhance osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC), leading to increased expression of crucial osteogenic genes. Further molecular mechanistic investigations reveal PMP1's activation of the PI3K-AKT-mTOR signaling pathway, a key element of its osteogenic effect. In vivo experiments utilizing a rat calvaria critical-sized defect model underscore the hydrogels' exceptional ability to accelerate new bone formation, thereby significantly advancing the restoration of calvaria defects. This research provides a promising bioactive material for bone tissue regeneration.

Adsorption processes for forming biomaterials of cellulose and hydroxyapatite for applications in bone tissue regeneration

Adsorption processes for forming biomaterials of cellulose and hydroxyapatite for applications in bone tissue regeneration

Combination of mesenchymal stem cell sheet with poly-caprolactone nanofibrous mat and Gelfoam increased osteogenesis capacity in rat calvarial defect

Introduction: To date, different strategies have been used for co-transplantation of cell-loaded biomaterials for bone tissue regeneration. This study aimed to investigate the osteogenic properties of adipose-derived-mesenchymal stem cell (AD-MSC) sheets combined with nanofibrous poly-caprolactone (PCL) mat and Gelfoam in rats with calvarial bone defect. Methods: Calvarial critical-size defects were induced in male rats. Animals were classified into Control, Gelfoam, Gelfoam/PCL nanofiber, Gelfoam/AD-MSC sheet, and Gelfoam/PCL nanofiber/AD-MSC sheet groups. After 3 months, rats were sacrificed and the regeneration rate was evaluated. Results: Almost all groups showed bone regeneration properties, but the volume of newly formed bone was higher in groups that received Gelfoam/AD-MSC and Gelfoam/PCL nanofiber/AD-MSC sheets (P < 0.05). The application of Gelfoam/PCL nanofiber/AD-MSC sheets not only increased bone thickness, bone volume/total bone volume (BV/TV) ratio, strong Hounsfield Unit (HU), but also led to the formation of ossified connective tissue with wrinkled patterns. Conclusion: The current study indicated that the Gelfoam/PCL nanofiber/AD-MSC sheet provides a suitable platform for effective osteogenesis in calvarial bone defects.

Enhanced bone regeneration with bioprinted GelMA/Bentonite scaffolds inspired by bone matrix

ABSTRACT In bone tissue engineering, the search for improved repair methods is crucial, given the drawbacks of traditional strategies like donor site issues and immune rejection. Addressing these challenges, this paper introduces an innovative GelMA/Bentonite composite bioink for 3D bioprinting, designed to create scaffolds that closely emulate native bone tissue. GelMA is selected for its biocompatibility and modifiable mechanics, while Bentonite's mineral richness and ion exchange capacity are harnessed to enhance scaffold structure and promote an osteogenic microenvironment. This research marks the inaugural incorporation of Bentonite into a bioink, a significant stride forward given its established safety in pharmaceuticals and versatility across industries. This bioink formulation signifies a breakthrough in bone tissue engineering, aiming to improve the osteointegration and regeneration of bone tissue. Combining Bentonite with GelMA marks a key step in creating bioinks that enhance bone healing, potentially transforming scaffold-based bone regeneration and pioneering the use of natural nanomaterials in medicine.

Strategically Designed Bifunctional Polydopamine Enwrapping Polycaprolactone-Hydroxyapatite-Doxorubicin Composite Nanofibers for Osteosarcoma Treatment and Bone Regeneration.

This study presents a new multifunctional nanofibrous drug delivery system to provide effective combination therapy with enormous potential for the treatment of osteosarcoma. We developed a composite nanofiber scaffold comprising poly(ε-caprolactone) (PCL) and hydroxyapatite (HAp)-loaded doxorubicin (DOX) coated with polydopamine (PDA) to combine cancer cell inhibition with bone tissue regeneration. DOX was conjugated with HAp and then mixed with a PCL solution to prepare a PCL/HAp-DOX (labeled PCLDH) nanofiber. Then, in situ polymerization of PDA on the PCLDH occurred to produce the PCLDH@PDA composite nanofiber. The morphology, XRD, FT-IR, wettability, photothermal characteristics, cumulative drug release, and in vitro bioactivities were evaluated. We found that the PDA coating not only enhanced the hydrophilic properties but also controlled drug release. The PCLDH@PDA composite scaffold significantly suppressed the proliferation of bone cancer cells initially and, consequently, improved the adhesion and proliferation of human mesenchymal stem cells (hMSCs). The PDA coating boosted the composite scaffold's bioactivity, as demonstrated through ALP activity, ARS assay, and biomineralization results. This strategy offers a promising dual-function scaffold to treat residual cancer and reconstruct defects after osteosarcoma surgery.

Biomimetic 3D printing of composite structures with decreased cracking

The development of tissue engineering and regeneration research has created new platforms for bone transplantation. However, the preparation of scaffolds with good fiber integrity is challenging, because scaffolds prepared by traditional printing methods are prone to fiber cracking during solvent evaporation. Human skin has an excellent natural heat-management system, which helps to maintain a constant body temperature through perspiration or blood-vessel constriction. In this work, an electrohydrodynamic-jet 3D-printing method inspired by the thermal-management system of skin was developed. In this system, the evaporation of solvent in the printed fibers can be adjusted using the temperature-change rate of the substrate to prepare 3D structures with good structural integrity. To investigate the solvent evaporation and the interlayer bonding of the fibers, finite-element analysis simulations of a three-layer microscale structure were carried out. The results show that the solvent-evaporation path is from bottom to top, and the strain in the printed structure becomes smaller with a smaller temperature-change rate. Experimental results verified the accuracy of these simulation results, and a variety of complex 3D structures with high aspect ratios were printed. Microscale cracks were reduced to the nanoscale by adjusting the temperature-change rate from 2.5 to 0.5 °C s−1. Optimized process parameters were selected to prepare a tissue engineering scaffold with high integrity. It was confirmed that this printed scaffold had good biocompatibility and could be used for bone-tissue regeneration. This simple and flexible 3D-printing method can also help with the preparation of a wide range of micro- and nanostructured sensors and actuators.

Specifics of Porous Polymer and Xenogeneic Matrices and of Bone Tissue Regeneration Related to Their Implantation into an Experimental Rabbit Defect.

This paper provides a study of two bone substitutes: a hybrid porous polymer and an osteoplastic matrix based on a bovine-derived xenograft. Both materials are porous, but their pore characteristics are different. The osteoplastic matrix has pores of 300-600 µm and the hybrid polymer has smaller pores, generally of 6-20 µm, but with some pores up to 100 µm across. SEM data confirmed the porometry results and demonstrated the different structures of the materials. Therefore, both materials were characterized by an interconnected porous structure and provided conditions for the adhesion and vital activity of human ASCs in vitro. In an experimental model of rabbit shin bone defect, it was shown that, during the 6-month observation period, neither of the materials caused negative reactions in the experimental animals. By the end of the observation period, restoration of the defects in animals in both groups was completed, and elements of both materials were preserved in the defect areas. Data from morphological examinations and CT data demonstrated that the rate of rabbit bone tissue regeneration with the hybrid polymer was comparable to that with the osteoplastic matrix. Therefore, the hybrid polymer has good potential for use in further research and improvement in biomedical applications.

Synthesis and biophysical characterization of porous bi-phase calcium phosphate/gelatin-PVA scaffold: Enhanced antibacterial, osteoconductivity and anticancer activity via silver nanoparticles and methotrexate incorporation

In our relentless pursuit of advancing bone tissue regeneration, we have meticulously crafted multifunctional scaffolds that transcend traditional approaches. These freeze-dried scaffolds, composed of biphasic calcium phosphate (BCP) intricately woven into a gelatin-polyvinyl alcohol (PVA) matrix, harbor the potential to revolutionize regenerative medicine. The scaffolds are characterized with XRD, FTIR, SEM, 3D images of the SEM, mechanical properties, swelling and degradation tests, drug release, cell viability, antibacterial and anticancer tests. Our in-situ synthesis of BCP within the PVA framework yielded a biphasic structure comprising hydroxyapatite (HAp) and beta-tricalcium phosphate. These scaffolds exhibit good mechanical compressive strength (ranging from 28 to 173 kPa) and boast high porosity levels (approaching 80 %) enhance the processes of nutrition and waste removal. The incorporation of silver nanoparticles (Ag) introduces antimicrobial prowess, resulting in a complex scaffold texture characterized by well-defined pores and rugged walls. The interconnectivity within this fibrous network contributes to enhanced mechanical properties. Additionally, our scaffolds facilitate the sustained release of methotrexate (MTX), a potent anticancer agent. Within the first day, MTX is promptly delivered, potentially impacting cancer cells. These Ag-containing scaffolds effectively combat common pathogens, demonstrating significant antibacterial activity as an essential property for preventing infections at the implantation site. Notably, our scaffolds, whether infused with Ag or MTX (at a concentration of 0.25 wt%), exhibit no toxic effects on Vero and MG-63 cells within a 24-hour window. However, higher Ag content (2.0 wt%) shows cytotoxicity. In summary, our multifaceted scaffolds, poised at the intersection of science and creativity, hold immense promise for bone tissue engineering. Further investigations will explore long-term effects, broader microbial contexts, and in vivo models.

Clinical potential of plasma-functionalized graphene oxide ultrathin sheets for bone and blood vessel regeneration: Insights from cellular and animal models

Graphene and graphene oxide (GO), due to their unique chemical and physical properties, possess biochemical characteristics that can trigger intercellular signals promoting tissue regeneration. Clinical applications of thin GO-derived sheets have inspired the development of various tissue regeneration and repair approaches. In this study, we demonstrate that ultrathin sheets of plasma-functionalized and reduced GO, with the oxygen content ranging from 3.2 % to 22 % and the nitrogen content from 0 % to 8.3 %, retain their essential mechanical and molecular integrity, and exhibit robust potential for regenerating bone tissue and blood vessels across multiple cellular and animal models. Initially, we observed the growth of blood vessels and bone tissue in vitro using these functionalized GO sheets on human adipose-derived mesenchymal stem cells and umbilical vein endothelial cells. Remarkably, our study indicates a 2.5-fold increase in mineralization and two-fold increase in tubule formation even in media lacking osteogenic and angiogenic supplements. Subsequently, we observed the initiation, conduction, and formation of bone and blood vessels in a rat tibial osteotomy model, evident from a marked 4-fold increase in the volume of low radio-opacity bone tissue and a significant elevation in connectivity density, all without the use of stem cells or growth factors. Finally, we validated these findings in a mouse critical-size calvarial defect model (33 % higher healing rate) and a rat skin lesion model (up to 2.5-fold increase in the number of blood vessels, and 35 % increase in blood vessels diameter). This study elucidates the pro-osteogenic and pro-angiogenic properties of both pristine and plasma-treated GO ultrathin films. These properties suggest their significant potential for clinical applications, and as valuable biomaterials for investigating fundamental aspects of bone and blood vessel regeneration.

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

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

Functionalizable bacterial cellulose composite membrane for guided tissue regeneration

This research aims to develop guided tissue regeneration (GTR) membranes from bacterial cellulose (BC), a natural polysaccharide-based biopolymer. A double-layered BC composite membrane was prepared by coating the BC membrane with mixed carboxymethyl cellulose/poly(ethylene oxide) (CMC/PEO) fibers via electrospinning. The CMC/PEO-BC membranes were then characterized for their chemical and physical characteristics. The 8 % (wt/v) CMC/PEO (1:1) aqueous solution yielded well-defined electrospun CMC/PEO nanofibers (125 ± 10 nm) without beads. The CMC/PEO-BC membranes exhibited good mechanical and swelling properties as well as good cytocompatibility against human periodontal ligament cells (hPDLs). Its functionalizability via carboxyl entities in CMC was tested using the calcium-binding domain of plant-derived recombinant human osteopontin (p-rhOPN-C122). As evaluated by enzyme-linked immunosorbent assay, a 98–99 % immobilization efficiency was achieved in a concentration-dependent manner over an applied p-rhOPN-C122 concentration range of 7.5–30 ng/mL. The biological function of the membrane was assessed by determining the expression levels of osteogenic-related gene transcripts using quantitative real-time reverse-transcriptase polymerase chain reaction. Mineralization assay indicated that the p-rhOPN-C122 immobilized CMC/PEO-BC membrane promoted hPDLs osteogenic differentiation. These results suggested that the developed membrane could serve as a promising GTR membrane for application in bone tissue regeneration.

Novel Organic-Inorganic Nanocomposite Hybrids Based on Bioactive Glass Nanoparticles and Their Enhanced Osteoinductive Properties.

Inorganic-organic hybrid biomaterials have been proposed for bone tissue repair, with improved mechanical flexibility compared with scaffolds fabricated from bioceramics. However, obtaining hybrids with osteoinductive properties equivalent to those of bioceramics is still a challenge. In this work, we present for the first time the synthesis of a class II hybrid modified with bioactive glass nanoparticles (nBGs) with osteoinductive properties. The nanocomposite hybrids were produced by incorporating nBGs in situ into a polytetrahydrofuran (PTHF) and silica (SiO2) hybrid synthesis mixture using a combined sol-gel and cationic polymerization method. nBGs ~80 nm in size were synthesized using the sol-gel technique. The structure, composition, morphology, and mechanical properties of the resulting materials were characterized using ATR-FTIR, 29Si MAS NMR, SEM-EDX, AFM, TGA, DSC, mechanical, and DMA testing. The in vitro bioactivity and degradability of the hybrids were assessed in simulated body fluid (SBF) and PBS, respectively. Cytocompatibility with mesenchymal stem cells was assessed using MTS and cell adhesion assays. Osteogenic differentiation was determined using the alkaline phosphatase activity (ALP), as well as the gene expression of Runx2 and Osterix markers. Hybrids loaded with 5, 10, and 15% of nBGs retained the mechanical flexibility of the PTHF-SiO2 matrix and improved its ability to promote the formation of bone-like apatite in SBF. The nBGs did not impair cell viability, increased the ALP activity, and upregulated the expression of Runx2 and Osterix. These results demonstrate that nBGs are an effective osteoinductive nanoadditive for the production of class II hybrid materials with enhanced properties for bone tissue regeneration.

3D printing of PEGDA/bioceramic for guiding cell adhesion and migration

The adhesion and migration characteristics of osteocytes on the surface of bone materials are crucial for bone tissue regeneration, which is conducive to the directional repair of bone defects. Herein, the adhesion and migration characteristics of MC3T3-E1 cells on the surface of SLA-3D printed PEGDA/bioceramic materials were analyzed in detail. The results indicated that, in comparison to the cured PEGDA matrix, the pseudopods of cells preferred to adhere to ceramic particles, demonstrating the characteristics of hard drive migration. Furthermore, on a wavy surface with a surface roughness (Ra=2 μm) fabricated by the laser of the SLA-3D printer, MC3T3-E1 cells could grow directionally along the rough channel via contact guidance. Therefore, by controlling the distribution of ceramic particles and adjusting the surface morphology of the printed PEGDA/bioceramic materials, the migration direction of cells can be dominated, which is of great significance for the targeted repair of bone tissue.

Gene regulatory network analysis identifies MYL1, MDH2, GLS, and TRIM28 as the principal proteins in the response of mesenchymal stem cells to Mg2+ ions

Magnesium (Mg)-based implants have emerged as a promising alternative for orthopedic applications, owing to their bioactive properties and biodegradability. As the implants degrade, Mg2+ ions are released, influencing all surrounding cell types, especially mesenchymal stem cells (MSCs). MSCs are vital for bone tissue regeneration, therefore, it is essential to understand their molecular response to Mg2+ ions in order to maximize the potential of Mg-based biomaterials. In this study, we conducted a gene regulatory network (GRN) analysis to examine the molecular responses of MSCs to Mg2+ ions. We used time-series proteomics data collected at 11 time points across a 21-day period for the GRN construction. We studied the impact of Mg2+ ions on the resulting networks and identified the key proteins and protein interactions affected by the application of Mg2+ ions. Our analysis highlights MYL1, MDH2, GLS, and TRIM28 as the primary targets of Mg2+ ions in the response of MSCs during 1–21 days phase. Our results also identify MDH2-MYL1, MDH2-RPS26, TRIM28-AK1, TRIM28-SOD2, and GLS-AK1 as the critical protein relationships affected by Mg2+ ions. By offering a comprehensive understanding of the regulatory role of Mg2+ ions on MSCs, our study contributes valuable insights into the molecular response of MSCs to Mg-based materials, thereby facilitating the development of innovative therapeutic strategies for orthopedic applications.

Hydroxypropyl methylcellulose/sodium alginate/hydroxyapatite nano biomaterial enriched with zinc to promote bone tissue augmentation

Bone is a dynamic connective tissue that provides structural support and locomotion to human physiology. Severe bone degeneration can occur in cases of trauma, infections, genetic disorders, tumors, and hormonal imbalances. This leads to a demand for scaffolds and composites to enhance bone tissue regeneration. The present study aimed to develop a composite material using hydroxypropyl methylcellulose and sodium alginate in combination with hydroxyapatite. The composite was doped with zinc and developed into a nanocomposite using ionic gelation and solvent precipitation methods. The prepared nanocomposite was characterized by scanning electron microscopy, atomic force microscopy, dynamic light scattering, FTIR, and XRD studies. In vivo pharmacological studies were conducted to establish the bone targeting and bone tissue regeneration efficacy of the developed nanocomposite. The nanocomposite was checked for cell toxicity by performing an MTT assay using MG63 cell line and the molecular mechanism of targeting efficiency was assessed by an in silico evaluation method. The results of the study confirmed the polymeric interlinking in the nanocomposite and the successful preparation of a composite material using biodegradable excipients. SEM and AFM studies indicated that the nanocomposite was within the 80–200 nm size range. MTT assay indicated that the developed nanocomposite was not cytotoxic and well tolerated by the MG63 cell line. In vivo, studies in validation with molecular docking evaluation suggested that the nanocomposite was effectively targeted to the bone and enhanced the bone density by blocking Farnesyl Diphosphate Synthetase (FDPS) in the mevalonate pathway which is essential for inhibiting the osteoclastic activity and promoting osteogenesis.