Adhesion Of Mesenchymal Stem Cells Research Articles

Comparative study on physicochemical properties of macroporous hydroxyapatite coatings on 316L stainless steel implants using sol-gel and inverse opal templating

This study focuses on enhancing metallic implant biocompatibility by fabricating a three-dimensional ordered macroporous hydroxyapatite (HAP) architecture through inverse opal technology. Utilizing colloidal crystal templates on 316L stainless steel, specifically with polystyrene and polymethyl methacrylate, successful fabrication was achieved through H2O2 plus H2SO4 etching. The calcination process at different temperatures (350, 500 and 700°C) resulted in distinct HAP structures, and the sample was calcined at 500°C (HAP500), exhibiting superior physicochemical properties, including enhanced crystallinity, surface roughness and wettability. Biological experiments demonstrated that HAP500 significantly promoted mesenchymal stem cell adhesion and proliferation compared to HAP350 and bare 316LSS, suggesting its potential as a highly effective medical device for bone implantation.

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.

Insights into adhesion and osteogenesis of bone marrow stromal cells promoted by surface nanopatterns

The surface property of biomaterials has a profound influence on the adhesion and biofunction of mesenchymal stem cells, which is vital for successful implantation and regeneration. Nanotopological surface is capable of mimicking bone's extracellular matrix (ECM) to regulate cell behavior, the understanding of which however remains elusive. In this study, we decoupled the effect of nanotopological cues from two perspectives: nanostructure and specific surface area. Bone marrow-derived mesenchymal stem cells (BMSCs) displayed stable and organized F-actin fibers, forming intricate myosin networks on the poly (ε-caprolactone) (PCL) substrate decorated with a well-defined nanopattern that was formed by the PCL lamellae. The cell spreading and myosin activation were limited when the specific surface area of the nanopattern was reduced. These findings illustrate that the specific surface area of the nanopatterned surface is a dominant regulator for cell mechanosensing. Our results highlight the potential of optimizing biomaterial interfaces to enhance cell adhesion and functionality for bone 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.

Highly biologically functional magnesium silicate-coated 3D printed round pore-shaped titanium scaffold alters exosomal miRNA expression to promote osteogenic differentiation for bone defect repair

Bone defects are a serious condition that has a significant impact on the function and quality of life of the patient. In severe bone defects, restoring the structure and function of bone tissue is a complex task, and titanium (Ti) implants designed with superior performance can be an alternative. In this study, in order to develop a Ti implant that effectively promotes osseointegration and new bone ingrowth, 3D printing-based magnesium silicate (MgSiO3)-coated round pore-shaped Ti scaffold (S-R/MgSi) was fabricated by standardizing pore size and porosity and designing different pore shapes and selecting the optimal pore shape (round) as well as subsequent hydrothermal synthesis to finally form MgSiO3 coating. The experimental results of Ti scaffolds with different pore shapes showed that S-R is optimal for promoting osteogenic differentiation. After S-R was coated with MgSiO3, S-R/MgSi enhanced the adhesion, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as regulated angiogenesis. In vivo studies, S-R/MgSi significantly promoted new bone ingrowth and was effective in repairing bone defects. Following the mechanism exploration, it was found that exosomes secreted by BMSCs co-cultured with S-R/MgSi (Exo_S-R/MgSi) were more able to promote the osteogenic differentiation of BMSCs. In conclusion, this study not only successfully prepared a new type of Ti implant with superior ability to promote new bone ingrowth, but also provided a new explanation for the mechanism of scaffold surface chemistry affecting osteogenesis from the viewpoint of scaffold surface coating affecting the amount and function of cellular exosome secretion.

Dynamic regulation of stem cell adhesion and differentiation on degradable piezoelectric poly (L-lactic acid) (PLLA) nanofibers.

Degradable piezoelectric materials possess significant potential for application in the realm of bone tissue regeneration. However, the correlation between cell regulation mechanisms and the dynamic variation caused by material degradation has not been explained, hindering the optimization of material design and its in vivo application. Herein, piezoelectric poly (L-lactic acid) (PLLA) nanofibers with different molecular weights (MW) were fabricated, and the effects of their piezoelectric properties, structural morphology, and material products during degradation on the adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) were investigated. Our results demonstrated that cell adhesion-mediated piezoelectric stimulation could significantly enhance cell spreading, cell orientation, and upregulate the expression of calmodulin, which further triggers downstream signaling cascade to regulate osteogenic differentiation markers of type I collagen and runt-related transcription factor 2. Additionally, during the degradation of the nanofibers, the piezoelectric properties of PLLA weakened, the fibrous structure gradually diminished, and pH levels in the vicinity decreased, which resulting in reduced osteogenic differentiation capability of MSCs. However, nanofibers with higher MW (280kDa) have the ability to maintain the fibrous morphology and piezoelectricity for a longer time, which can regulate the osteogenic differentiation of stem cells for more than 4 weeks. These findings have provide a new insight to correlate cell behavior with MW and the biodegradability of piezopolymers, which revealed an active method for cell regulation through material optimization for bone tissue engineering in near future.

Chitosan-PNIPAM Thermogel Associated with Hydrogel Microspheres as a Smart Formulation for MSC Injection.

Regenerative medicine based on cell therapy has emerged as a promising approach for the treatment of various medical conditions. However, the success of cell therapy heavily relies on the development of suitable injectable hydrogels that can encapsulate cells and provide a conducive environment for their survival, proliferation, and tissue regeneration. Herein, we address the medical need for cyto- and biocompatible injectable hydrogels by reporting on the synthesis of a hydrogel-forming thermosensitive copolymer. The copolymer was synthesized by grafting poly(N-isopropylacrylamide-co-carboxymethyl acrylate) (PNIPAM-COOH) onto chitosan through amide coupling. This chemical modification resulted in the formation of hydrogels that exhibit a sol-gel transition with an onset at approximately 27 °C, making them ideal for use in injectable applications. The hydrogels supported the survival and proliferation of cells for several days, which is critical for cell encapsulation. Furthermore, the study evaluates the addition of collagen/chitosan hybrid microspheres to support the adhesion of mesenchymal stem cells within the hydrogels. Altogether, these results demonstrate the potential of the PNIPAM-chitosan thermogel for cell encapsulation and its possible applications in regenerative medicine.

Synergistic large segmental bone repair by 3D printed bionic scaffolds and engineered ADSC nanovesicles: Towards an optimized regenerative microenvironment

Achieving sufficient bone regeneration in large segmental defects is challenging, with the structure of bone repair scaffolds and their loaded bioactive substances crucial for modulating the local osteogenic microenvironment. This study utilized digital laser processing (DLP)-based 3D printing technology to successfully fabricate high-precision methacryloylated polycaprolactone (PCLMA) bionic bone scaffold structures. Adipose-derived stem cell-engineered nanovesicles (ADSC-ENs) were uniformly and stably modified onto the bionic scaffold surface using a perfusion device, constructing a conducive microenvironment for tissue regeneration and long bone defect repair through the scaffold's structural design and the vesicles' biological functions. Scanning electron microscopy (SEM) examination of the scaffold surface confirmed the efficient loading of ADSC-ENs. The material group loaded with vesicles (PCLMA-BAS-ENs) demonstrated good cell compatibility and osteogenic potential when analyzed for the adhesion and osteogenesis of primary rabbit bone marrow mesenchymal stem cells (BMSCs) on the material surface. Tested in a 15 mm critical rabbit radial defect model, the PCLMA-BAS-ENs scaffold facilitated near-complete bone defect repair after 12 weeks. Immunofluorescence and proteomic results indicated that the PCLMA-BAS-ENs scaffold significantly improved the osteogenic microenvironment at the defect site in vivo, promoted angiogenesis, and enhanced the polarization of macrophages towards M2 phenotype, and facilitated the recruitment of BMSCs. Thus, the PCLMA-BAS-ENs scaffold was proven to significantly promote the repair of large segmental bone defects. Overall, this strategy of combining engineered vesicles with highly biomimetic scaffolds to promote large-segment bone tissue regeneration holds great potential in orthopedic and other regenerative medicine applications.

Plasma bias homopolar sputtering technology and its application to enhance bioactivity of polyetheretherketone surface

Numerous strategies have been developed to deposit metal-based films on biomedical implants to improve their performances. As a promising strategy, vacuum plasma plating technology can introduce many bioactive metals on the implant surface and achieve strong interfacial bonding. However, there are still limitations in the surface modification of a non-conductive matrix. Here, a simple and universal plasma-based technique termed plasma bias homopolar sputtering (PBHS) was presented to modify the insulating and conductive materials. The technical principles and characteristics of PBHS were comprehensively studied. As a demonstration, the Fe-based film was prepared on the surface of an insulating polyetheretherketone (PEEK) by PBHS to improve its biological performance. The as-prepared Fe-based film exhibited low elasticity modulus and good hydrophilicity, enhancing the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells. This work provides a simple and universal technique for the preparation of metal-based films, holding great potential for the surface modification of biomedical implants.

Porous Titanium/SF Sponge Composite Scaffold with Loads of Gentamicin and Small Extracellular Vesicles to Improve Antibacterial and Osteogenesis Properties

AbstractAdditive manufacturing has been widely used for producing porous titanium orthopedic implants. However, the higher surface area inherent to porous structures increases the risk of bacterial colonization. In this work, composite scaffolds with dual functions of the antibacterial and osteogenesis promotion properties are developed. The porous titanium is fabricated using a selective laser melting process to provide mechanical support. Silk fibrin (SF) sponge‐loading gentamicin and extracellular vesicles (EVs) are prepared in the pores of the porous titanium. The developed composite scaffolds are investigated for their antibacterial and osteogenesis effects. The samples exhibit well antibacterial activity against Escherichia coli. The samples also show good cytocompatibility, effectively promoting the adhesion and proliferation of the bone marrow mesenchymal stem cells (rBMSCs). EVs significantly promote the expression of osteogenesis‐related genes in rBMCSs and the superior extracellular matrix mineralization reveals that EVs have a remarkable role in enhancing osteogenic differentiation. Therefore, the composite scaffolds with dual functions of antibacterial and osteogenesis promotion properties have excellent potential for orthopedic implant applications.

A Multifunctional Metal-Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation.

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

Self-Assembled DNA Composite-Engineered Mesenchymal Stem Cells for Improved Skin-Wound Repair.

The direct use of mesenchymal stem cells (MSCs) as therapeutics for skin injuries is a promising approach, yet it still faces several obstacles, including limited adhesion, retention, and engraftment of stem cells in the wound area, as well as impaired regenerative and healing functions. Here, DNA-based self-assembled composites are reported that can aid the adhesion of MSCs in skin wounds, enhance MSC viability, and accelerate wound closure and re-epithelialization. Rolling-circle amplification (RCA)-derived DNA flowers, equipped with multiple copies of cyclic Arg-Gly-Asp (cRGD) peptides and anti-von Willebrand factor (vWF) aptamers, act as robust scavengers of reactive oxygen species (ROS) and enable synergistic recognition and adhesion to stem cells and damaged vascular endothelial cells. These DNA structure-aided stem cells are retained at localized wound sites, maintain repair function, and promote angiogenesis and growth factor secretion. In both normal and diabetes-prone db/db mice models with excisional skin injuries, facile topical administration of DNA flower-MSCs elicits rapid blood vessel formation and enhances the sealing of the wound edges in a single dose. DNA composite-engineered stem cells warrant further exploration as a new strategy for the treatment of skin and tissue damage.

Enhancing the angiogenesis and osteogenesis of low elastic modulus Ti-Nb-Zr-Sn alloy surface through grafting growth factors-containing gelatin nanoparticles

The study aimed to apply a multiple surface modification for low elastic modulus Ti-24 % Nb-4 % Zr-8 % Sn (Ti2448) alloy, to enhance its biological properties for bone implant applications. We employed a combined sandblasting/acid etching/alkaline etching process to modify the Ti2448 alloy surfaces with mixed nano/submicron/micron-scaled pits and super wettability. We prepared gelatin nanoparticles (GNPs) loaded with growth factors: vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) and/or bone morphogenetic protein-2 (BMP-2). The growth factors-containing GNPs were then sequentially grafted onto the surface-modified Ti2448 alloy in a layered (single layer: BMP-2 or VEGF/PDGF; double layer: inner BMP-2 and outer VEGF/PDGF) or mixed BMP-2/VEGF/PDGF manner. Surface characterizations, including morphology, roughness, surface energy, and cytotoxicity, of Ti2448 alloy were analyzed. For biological response, we investigated the tube formation ability of human umbilical vein endothelial cells (HUVECs) and the cell responses (adhesion, proliferation, and mineralization) of human bone marrow mesenchymal stem cells (hMSCs). The results demonstrated the successful preparation of GNPs with 200∼300 nm particle size and their successful loading with the growth factors using natural crosslinker genipin. The growth factor-containing GNPs were effectively grafted onto the surface-modified hydrophilic Ti2448 alloy without significantly reducing its wettability (water contact angle remained below 40°). The results of the study showed that the GNPs-grafted Ti2448 alloy surfaces, with the GNPs loaded with VEGF/PDGF and/or BMP-2, exhibited enhanced biological properties. The GNPs-grafted surfaces were found to be non-toxic and capable of promoting tube formation of HUVECs, particularly when single VEGF/PDGF layer or double (inner BMP-2/ outer VEGF/PDGF) layer was loaded on GNPs (enhancing the cumulative tube length approximately 1.4 times that of no GNPs-grafted surfaces). Moreover, the GNPs-grafted surfaces enhanced the adhesion-related proteins and extracellular matrix mineralization of hMSCs, particularly with the loading of single VEGF/PDGF or mixed VEGF/PDGF/BMP-2 on GNPs (enhancing αvβ3 integrin patch number > 3.5 times, vinculin patch number > 2 times, and mineralization approximately 1.4 times). Based on these findings, we concluded that the proposed Ti2448 alloy surfaces, when grafted with VEGF/PDGF- and/or BMP-2-containing GNPs, have the potential for bone implant applications. The surface modifications on the Ti2448 alloy may promote angiogenesis in the early stage of bone repair (through VEGF/PDGF) and osteogenesis in the late stage (through BMP-2), thereby accelerating the overall bone healing process.

A facile Immunoregulatory Constructional Design by Proanthocyanidin Optimizing Directional Chitosan Microchannel.

Improving the interconnected structure and bioregulatory function of natural chitosan is beneficial for optimizing its performance in bone regeneration. Here, a facile immunoregulatory constructional design is proposed for developing instructive chitosan by directional freezing and alkaline salting out. The molecular dynamics simulation confirmed the assembly kinetics and structural features of various polyphenols and chitosan molecules. Along with the in vitro anti-inflammatory, antioxidative, promoting bone mesenchymal stem cell (BMSC) adhesion and proliferation performance, proanthocyanidin optimizing chitosan (ChiO) scaffold presented an optimal immunoregulatory structure with the directional microchannel. Transcriptome analysis in vitro further revealed the cytoskeleton- and immune-regulation effect of ChiO are the key mechanism of action on BMSC. The rabbit cranial defect model (Φ = 10mm) after 12 weeks of implantation confirmed the significantly enhanced bone reconstitution. This facile immunoregulatory directional microchannel design provides effective guidance for developing inducible chitosan scaffolds.

Mesenchymal stem cells in PRP and PRF containing poly(3-caprolactone)/gelatin Scaffold: a comparative in-vitro study.

Scaffold design is one of the three most essential parts of tissue engineering. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) have been used in clinics and regenerative medicine for years. However, the temporal release of their growth factors limits their efficacy in tissue engineering. In the present study, we planned to synthesize nanofibrous scaffolds with the incorporation of PRP and PRF by electrospinning method to evaluate the effect of the release of PRP and PRF growth factors on osteogenic gene expression, calcification, proliferation, and cell adhesion of human bone marrow mesenchymal stem cell (h-BMSC) as they are part of scaffold structures. Therefore, we combined PRP/PRF, derived from the centrifugation of whole blood, with gelatin and Polycaprolactone (PCL) and produced nanofibrous electrospun PCL/Gel/PRP and PCL/Gel/PRF scaffolds. Three groups of scaffolds were fabricated, and h-BMSCs were seeded on them: (1) PCL/Gel; (2) PCL/Gel/PRP; (3) PCL/Gel/PRF. MTS assay was performed to assess cell proliferation and adhesion, and alizarin red staining confirmed the formation of bone minerals during the experiment. The result indicated that PCL/Gel did not have any better outcomes than the PRP and PRF group in any study variants after the first day of the experiment. PCL/gelatin/PRF was more successful regarding cell proliferation and adhesion. Although PCL/gelatin/PRP showed more promising results on the last day of the experiment in mineralization and osteogenic gene expression, except RUNX2, in which the difference with PCL/gelatin/PRF group was not significant.

Hierarchical Scaffold with Directional Microchannels Promotes Cell Ingrowth for Bone Regeneration.

Bone regenerative scaffolds with a bionic natural bone hierarchical porous structure provide a suitable microenvironment for cell migration and proliferation. Here, a bionic scaffold (DP-PLGA/HAp) with directional microchannels is prepared by combining 3D printing and directional freezing technology. The 3D printed framework provides structural support for new bone tissue growth, while the directional pore embedded in the scaffolds provides an express lane for cell migration and nutrition transport, facilitating cell growth and differentiation. The hierarchical porous scaffolds achieve rapid infiltration and adhesion of bone marrow mesenchymal stem cells (BMSCs) and improve the expression of osteogenesis-related genes. The rabbit cranial defect experiment presents significant new bone formation, demonstrating that DP-PLGA/HAp offers an effective means to guide cranial bone regeneration. The combination of 3D printing and directional freezing technology might be a promising strategy for developing bone regenerative biomaterials.

Enhanced Osteogenic Activity and Antibacterial Properties of Graphene Oxide-Poly(Lactic Acid) Films for the Repair of Cranial Defects in Rats

The failure of bone defect repair caused by bacterial infection is a significant clinical challenge. However, the currently utilized bone graft materials lack antibacterial properties, necessitating the development of bone repair materials with both osteoinductive and antibacterial capabilities. Graphene oxide (GO) has garnered considerable attention due to its distinctive physical, chemical, and biological characteristics. In this study, we prepared a graphene oxide-poly(lactic acid) (GO-PLA) film with exceptional biological properties. In vitro investigations demonstrated that the GO-PLA film substantially enhanced the adhesion and proliferation capacity of rat bone marrow mesenchymal stem cells (rBMSCs). Furthermore, we observed augmented alkaline phosphatase activity as well as increased expression levels of osteogenic genes in rBMSCs cultured on the GO-PLA film. Additionally, we evaluated the antibacterial activity of our samples using gram-positive Streptococcus mutans (Sm) and gram-negative Actinobacillus actinomycetemcomitans (Aa). Our findings revealed that GO doping significantly inhibited bacterial growth. Moreover, implantation experiments conducted on rat skull defects demonstrated excellent guided bone regeneration performance exhibited by the GO-PLA film. Overall, our results indicate that the GO-PLA film possesses outstanding osteogenic and antibacterial properties, making it a promising biomaterial for bone tissue regeneration.

Neoteric Semiembedded β-Tricalcium Phosphate Promotes Osteogenic Differentiation of Mesenchymal Stem Cells under Cyclic Stretch.

β-Tricalcium phosphate (β-TCP) is a bioactive material for bone regeneration, but its brittleness limits its use as a standalone scaffold. Therefore, continuous efforts are necessary to effectively integrate β-TCP into polymers, facilitating a sturdy ion exchange for cell regulation. Herein, a novel semiembedded technique was utilized to anchor β-TCP nanoparticles onto the surface of the elastic polymer, followed by hydrophilic modification with the polymerization of dopamine. Cell adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) under static and dynamic uniaxial cyclic stretching conditions were investigated. The results showed that the new strategy was effective in promoting cell adhesion, proliferation, and osteogenic induction by the sustained release of Ca2+ in the vicinity and creating a reasonable roughness. Specifically, released Ca2+ from β-TCP could activate the calcium signaling pathway, which further upregulated calmodulin and calcium/calmodulin-dependent protein kinase II genes in MSCs. Meanwhile, the roughness of the membrane and the uniaxial cyclic stretching activated the PIEZO1 signaling pathway. Chemical and mechanical stimulation promotes osteogenic differentiation and increases the expression of related genes 2-8-fold. These findings demonstrated that the neoteric semiembedded structure was a promising strategy in controlling both chemical and mechanical factors of biomaterials for cell regulation.

The effect of nano-natural biomaterial on stimulation of RADMSCs toward osteogenesis: an in vitro study

In recent years, natural biomaterials have been the focal point of most biomedical investigations. To prepare the Ostrich Eggshell/Hydroxyapatite (OE/HA) powder scaffolds, OE powder was immersed in 1% Triton X-100 for 24 h and then autoclaved twice. Medical grade HA was combined with pulverized OE at different ratios to yield three different OE/HA powder scaffolds. The resultant scaffolds underwent characterization experiments using different techniques, including FTIR, XRD, radiography, and SEM analyses. Rabbit adipose-derived mesenchymal stem cells (RADMSCs) were isolated from adipose tissues and characterized by flow cytometry. A direct contact test was performed for the cytotoxicity test using L929 cells. Cell adhesion was validated using SEM imaging, viability was assessed using DAPI and Annexin V/PI staining, and osteogenic differentiation was investigated using the ALP assay. The cytotoxicity assay using L929 cells verified that the OE/HA powder scaffold is safe and further functional experiments could be carried out. Behavioral assays, radiography, surface markers, surface topography analyses, and viability tests yielded promising results confirming cellular acceptance of the scaffold. In the present study, we provided evidence that the prepared OE/HA scaffold is not only cytocompatible but also can enhance mesenchymal stem cell adhesion, growth, and osteogenic differentiation in vitro.

PVTF Nanoparticles/PLA Electroactive Degradable Membrane for Bone Tissue Regeneration

Electroactive biomaterials can influence the microenvironment between cells and a material’s surface by controlling surface electrical signals, thereby affecting cellular physiological activities. As the most commonly used ferroelectric polymer, Poly(vinylidene fluoride-trifluoroethylene) (PVTF) has attracted widespread attention due to its good stability, biocompatibility and mechanical properties. However, it has limitations such as non-degradability. In this study, PVTF nanoparticles (PVTF NPs), prepared using a phase separation method, were compounded with polylactide (PLA) to prepare PVTF NPs/PLA composite membrane (PN/PLA), which simultaneously achieved electroactivity and degradability. PVTF NPs containing ferroelectric β phase were evenly distributed on the PLA substrate, forming negative potential spots through corona polarization. The PLA substrate gradually degraded in a simulated body fluid environment. The negative surface potential provided by PVTF NPs in PN/PLA enhanced the adhesion, proliferation, and early-stage osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The electrical bioactivity and degradability could be joined together in this study, which is promising for tissue regeneration biomaterials, such as guided bone regeneration membrane.