Adhesion Of Mesenchymal Stem Cells Research Articles

Silver-quercetin-loaded honeycomb-like Ti-based interface combats infection-triggered excessive inflammation via specific bactericidal and macrophage reprogramming

Excessive inflammation caused by bacterial infection is the primary cause of implant failure. Antibiotic treatment often fails to prevent peri-implant infection and may induce unexpected drug resistance. Herein, a non-antibiotic strategy based on the synergy of silver ion release and macrophage reprogramming is proposed for preventing infection and bacteria-induced inflammation suppression by the organic-inorganic hybridization of silver nanoparticle (AgNP) and quercetin (Que) into a polydopamine (PDA)-based coating on the 3D framework of porous titanium (SQPdFT). Once the planktonic bacteria (e.g., Escherichia coli, Staphylococcus aureus) reach the surface of SQPdFT, released Que disrupts the bacterial membrane. Then, AgNP can penetrate the invading bacterium and kill them, which further inhibits the biofilm formation. Simultaneously, released Que can regulate macrophage polarization homeostasis via the peroxisome proliferators-activated receptors gamma (PPARγ)-mediated nuclear factor kappa-B (NF-κB) pathway, thereby terminating excessive inflammatory responses. These advantages facilitate the adhesion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), concomitantly suppressing osteoclast maturation, and eventually conferring superior mechanical stability to SQPdFT within the medullary cavity. In summary, owing to its excellent antibacterial effect, immune remodeling function, and pro-osteointegration ability, SQPdFT is a promising protective coating for titanium-based implants used in orthopedic replacement surgery.

In vitro evaluation of the biocompatibility and bioactivity of a SLM-fabricated NiTi alloy with superior tensile property

Because nickel-titanium (NiTi) alloys have unique functions, such as superelasticity, shape memory, and hysteresis similar to bone in the loading-unloading cycles of their recoverable deformations. They likely offer good bone integration, a low loosening rate, individual customization, and ease of insertion. Due to the poor processability of NITI, traditional methods cannot manufacture NiTi products with complex shapes. Orthopedic NiTi implants need to show an adequate fracture elongation of at least 8%. Additive manufacturing can be used to prepare NiTi implants with complex structures and tunable porosity. However, as previously reported, additively manufactured NiTi alloys could only exhibit a maximum tensile fracture strain of 7%. In new reports, a selective laser melting (SLM)–NiTi alloy has shown greater tensile strain (15.6%). Nevertheless, due to the unique microstructure of additive manufacturing NiTi that differs from traditional NITI, the biocompatibility of SLM-NITI manufactured by this new process requires further evaluation In this study, the effects of the improved NiTi alloy on bone marrow mesenchymal stem cell (BMSC) proliferation, adhesion, and cell viability were investigated via in vitro studies. A commercial Ti-6Al-4V alloy was studied side-by-side for comparison. Like the Ti-6Al-4V alloy, the SLM-NiTi alloy exhibited low cytotoxicity toward BMSCs and similar effect on cell adhesion or cell viability. This study demonstrates that the new SLM-NiTi alloy, which has exhibited improved mechanical properties, also displays excellent biocompatibility. Therefore, this alloy may be a superior implant material in biomedical implantation.Graphical

Functionalization of Alginate Hydrogels with a Multifunctional Peptide Supports Mesenchymal Stem Cell Adhesion and Reduces Bacterial Colonization.

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1-11 region of lactoferrin (LF). The RGD-LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide-functionalized hydrogels was excellent, with values higher than 85 % at day 1, and higher than 95 % after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram-positive and Gram-negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels.

Effect of nanodiamonds surface deposition on hydrophilicity, bulk degradation and in-vitro cell adhesion of 3D-printed polycaprolactone scaffolds for bone tissue engineering

This study was designed to deposit nanodiamonds (NDs) on 3D-printed poly-ϵ-caprolactone (PCL) scaffolds and evaluate their effect on the surface topography, hydrophilicity, degradation, andin-vitrocell adhesion compared to untreated PCL scaffolds. The PCL scaffold specimens were 3D-printed by fused deposition modeling (FDM) technique with specific porosity parameters. The 3D-printed specimens' surfaces were modified by NDs deposition followed by oxygen plasma post-treatment using a plasma focus device and a non-thermal atmospheric plasma jet, respectively. Specimens were evaluated through morphological characterization by field emission scanning electron microscope (FESEM), microstructure characterization by Raman spectroscopy, chemical characterization by Fourier transform infrared (FTIR) spectroscopy, hydrophilicity degree by contact angle and water uptake measurements, andin-vitrodegradation measurements (n= 6). In addition,in-vitrobone marrow mesenchymal stem cells adhesion was evaluated quantitatively by confocal microscopy and qualitatively by FESEM at different time intervals after cell seeding (n= 6). The statistical significance level was set atp⩽ 0.05. The FESEM micrographs, the Raman, and FTIR spectra confirmed the successful surface deposition of NDs on scaffold specimens. The NDs treated specimens showed nano-scale features distributed homogeneously across the surface compared to the untreated ones. Also, the NDs treated specimens revealed a statistically significant smaller contact angle (17.45 ± 1.34 degrees), higher water uptake percentage after 24 h immersion in phosphate buffer saline (PBS) (21.56% ± 1.73), and higher degradation rate after six months of immersion in PBS (43.92 ± 0.77%). Moreover, enhanced cell adhesion at all different time intervals was observed in NDs treated specimens with higher nuclei area fraction percentage (69.87 ± 3.97%) compared to the untreated specimens (11.46 ± 1.34%). Surface deposition of NDs with oxygen-containing functional groups on 3D-printed PCL scaffolds increased their hydrophilicity and degradation rate with significant enhancement of thein-vitrocell adhesion compared to untreated PCL scaffolds.

Chemical Modification of Nanocrystalline Cellulose for Manufacturing of Osteoconductive Composite Materials.

Cellulose is one of the main renewable polymers whose properties are very attractive in many fields, including biomedical applications. The modification of nanocrystalline cellulose (NCC) opens up the possibility of creating nanomaterials with properties of interest as well as combining them with other biomedical polymers. In this work, we proposed the covalent modification of NCC with amphiphilic polyanions such as modified heparin (Hep) and poly(αL-glutamic acid) (PGlu). The modification of NCC should overcome two drawbacks in the production of composite materials based on poly(ε-caprolactone) (PCL), namely, (1) to improve the distribution of modified NCC in the PCL matrix, and (2) to provide the composite material with osteoconductive properties. The obtained specimens of modified NCC were characterized by Fourier-transform infrared spectroscopy and solid-state 13C nuclear magnetic resonance spectroscopy, dynamic and electrophoretic light scattering, as well as thermogravimetric analysis. The morphology of PCL-based composites containing neat or modified NCC as filler was studied by optical and scanning electron microscopy. The mechanical properties of the obtained composites were examined in tensile tests. The homogeneity of filler distribution as well as the mechanical properties of the composites depended on the method of NCC modification and the amount of attached polyanion. In vitro biological evaluation showed improved adhesion of human fetal mesenchymal stem cells (FetMSCs) and human osteoblast-like cells (MG-63 osteosarcoma cell line) to PCL-based composites filled with NCC bearing Hep or PGlu derivatives compared to pure PCL. Furthermore, these composites demonstrated the osteoconductive properties in the experiment on the osteogenic differentiation of FetMSCs.

Multi-parameter design of triply periodic minimal surface scaffolds: from geometry optimization to biomechanical simulation

This study introduces a multi-parameter design methodology to create triply periodic minimal surface (TPMS) scaffolds with predefined geometric characteristics. The level-set constant and unit cell lengths are systematically correlated with targeted porosity and minimum pore sizes. Network and sheet scaffolds featuring diamond, gyroid, and primitive level-set structures are generated. Three radially graded schemes are applied to each of the six scaffold type, accommodating radial variations in porosity and pore sizes. Computer simulations are conducted to assess the biomechanical performance of 18 scaffold models. Results disclose that diamond and gyroid scaffolds exhibit more expansive design ranges than primitive counterparts. While primitive scaffolds display the highest Young’s modulus and permeability, their lower yield strength and mesenchymal stem cell (MSC) adhesion render them unsuitable for bone scaffolds. Gyroid scaffolds demonstrate superior mechanical and permeability performances, albeit with slightly lower MSC adhesion than diamond scaffolds. Sheet scaffolds, characterized by more uniform material distribution, exhibit superior mechanical performance in various directions, despite slightly lower permeability. The higher specific surface area of sheet scaffolds contributes to elevated MSC adhesion. The stimulus factor analysis also revealed the superior differentiation potential of sheet scaffolds over network ones. The diamond sheet type demonstrated the optimal differentiation. Introducing radial gradations enhances axial mechanical performance at the expense of radial mechanical performance. Radially decreasing porosity displays the highest permeability, MSC adhesion, and differentiation capability, aligning with the structural characteristics of human bones. This study underscores the crucial need to balance diverse biomechanical properties of TPMS scaffolds for bone tissue engineering.

Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

Improved biocompatibility and osteogenesis of porous graphene oxide/silk fibroin scaffold for potential applications in bone tissue engineering

To better mimic the inherent porous architecture of the natural bone, we fabricated graphene oxide/silk fibroin (GO/SF) scaffolds using a salting leaching method, followed by in situ reduction and reinforcement with ascorbic acid. SEM images revealed that the scaffolds exhibited an interconnectivity porous structure both on the surface and throughout the interior. We found that the pore size could be readily adjusted by varying the concentration of GO in the scaffolds. FTIR results demonstrated that the addition of GO didn’t form chemical interaction between GO and SF, but it significantly increased the content of β-sheet structure from 46.36 % to 51.12 % and improved the thermal stability of the scaffolds. Moreover, the reduced graphene oxide/silk fibroin (rGO/SF) scaffolds exhibited a superior capacity to promote the adhesion, proliferation, and mineral deposition of mouse mesenchymal stem cell (MSCs) when compared to pure SF scaffolds. Notably, the equilibrium Young's modulus of the scaffolds gradually increased from 5.5±0.5 KPa to 14.6±2.1 KPa with the increment of rGO content. Osteogenic differentiation with higher BSP (2. 84-fold) and RUNX2 (2.91-fold) expression level was also observed in 3 % rGO scaffold, suggesting a strong inclination towards bone formation. Based on these findings, the prepared rGO/SF scaffold in this study hold great potential as a viable option for bone tissue engineering.

Epoxidized Soybean Oleic Acid/Oligomeric Poly(lactic acid)-Grafted Nano-Hydroxyapatite and Its Role as a Filler in Poly(L-lactide) for Potential Bone Fixation Application.

One of the most effective strategies for modifying the surface properties of nano-fillers and enhancing their composite characteristics is through polymer grafting. In this study, a coprecipitation method was employed to modify hydroxyapatite (HAP) with epoxidized soybean oleic acid (ESOA), resulting in ESOA-HAP. Subsequently, oligomeric poly(lactic acid) (OPLA) was grafted onto the surface of ESOA-HAP, yielding OPLA-ESOA-HAP. HAP, ESOA-HAP, and OPLA-ESOA-HAP were comprehensively characterized. The results demonstrate the progressive grafting of ESOA and OPLA onto the surface of HAP, resulting in enhanced hydrophobicity and improved dispersity in organic solvent for OPLA-ESOA-HAP compared to HAP. The vitality and adhesion of Wistar rat mesenchymal stem cells (MSCs) were assessed using HAP and modified HAP materials. Following culture with MSCs for 72 h, the OPLA-ESOA-HAP showed an inhibition rate lower than 23.0% at a relatively high concentration (1.0 mg/mL), which is three times lower compared to HAP under similar condition. The cell number for OPLA-ESOA-HAP was 4.5 times higher compared to HAP, indicating its superior biocompatibility. Furthermore, the mechanical properties of the OPLA-ESOA-HAP/PLLA composite almost remained unaltered ever after undergoing two stages of thermal processing involving melt extrusion and inject molding. The increase in the biocompatibility and relatively high mechanical properties render OPLA-ESOA-HAP/PLLA a potential material for the biodegradable fixation system.

A comparative study of 3D-printed scaffolds fabricated from different hydroxyapatite sources for bone tissue engineering applications

As a naturally occurring mineral component of bone, hydroxyapatite (HA) is a preferred bone-repair material in clinical medicine. This adaptable biomaterial is developed from synthetic or biological sources. The goal of this study was to investigate the physicochemical and biological properties of scaffolds made from diverse hydroxyapatite sources. We prepared hydroxyapatite powders either from naturally occurring sources, using decellularized bone extracellular matrix (DBECM) and deproteinized bovine bone (DBB), or in the laboratory using the co-precipitation method. Although XRD analysis confirmed the pure phase of HA in all three powders, XRF data found some other trace elements in bone-derived biomaterials, such as magnesium and strontium. Further, FTIR spectra showed DBECM-associated macromolecule peaks. In the second phase of this study, the particles were mixed with sodium alginate to produce bioink for 3D printing via extrusion. SEM photographs of the printed scaffolds showed a grid-like porous structure with large, interconnected pores. Although all of the scaffolds retained their structural integrity after 28 days submerged in the culture medium, DBECM-based scaffolds degraded the most. The test of Young’s modulus and compressive strength of scaffolds revealed that all scaffolds are strong enough to be employed in non-weight-bearing applications. The biological characteristics of the scaffolds were then evaluated via cytotoxicity analysis, SEM examination of cell attachment, MTT assay, ALP activity assessment, immunofluorescence staining, and Alizarin red staining. The results indicated that all three scaffolds provided a surface that promoted adhesion and proliferation of rat bone marrow mesenchymal stem cells (rMSCs), as well as stimulated the production of mineralized extracellular matrices. Additionally, our findings showed that scaffolds made from DBECM powders offer the best environment for cell activity. This is most likely due to the presence of trace elements and protein macromolecules in DBECM powders that are not found in DBB and synthetic HA. In conclusion, our comparative study revealed that while all three scaffolds are suitable for bone tissue engineering, DBECM-based scaffolds outperform DBB and synthetic HA.

Activating Angiogenesis and Immunoregulation to Propel Bone Regeneration via Deferoxamine-Laden Mg-Mediated Tantalum Oxide Nanoplatform.

Vascularization and inflammation management are essential for successful bone regeneration during the healing process of large bone defects assisted by artificial implants/fillers. Therefore, this study is devoted to the optimization of the osteogenic microenvironment for accelerated bone healing through rapid neovascularization and appropriate inflammation inhibition that were achieved by applying a tantalum oxide (TaO)-based nanoplatform carrying functional substances at the bone defect. Specifically, TaO mesoporous nanospheres were first constructed and then modified by functionalized metal ions (Mg2+) with the following deferoxamine (DFO) loading to obtain the final product simplified as DFO-Mg-TaO. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the product was homogeneously dispersed hollow nanospheres with large specific surface areas and mesoporous shells suitable for loading Mg2+ and DFO. The biological assessments indicated that DFO-Mg-TaO could enhance the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The DFO released from DFO-Mg-TaO promoted angiogenetic activity by upregulating the expressions of hypoxia-inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF). Notably, DFO-Mg-TaO also displayed anti-inflammatory activity by reducing the expressions of pro-inflammatory factors, benefiting from the release of bioactive Mg2+. In vivo experiments demonstrated that DFO-Mg-TaO integrated with vascular regenerative, anti-inflammatory, and osteogenic activities significantly accelerated the reconstruction of bone defects. Our findings suggest that the optimized DFO-Mg-TaO nanospheres are promising as multifunctional fillers to speed up the bone healing process.

Cobalt-containing calcium silicate nanowires incorporated scaffolds for the repair of osteochondral defect induced by chondrosarcoma

Considering the difficulty in the treatment of chondrosarcoma in clinic, multifunctional composite hydrogel scaffolds were designed with excellent photothermal ability for the regeneration of damaged bone and cartilage tissue. The chitosan solution/polyvinyl alcohol (CP) hydrogels with different contents of cobalt doped calcium silicate (Co-CSH) nanowires were prepared via 3D printing method. Attributing to the excellent photothermal performance of Co-CSH nanowires, the average survival rate of human chondrosarcoma cells in the CP-5Co-13.4 % and CP-5Co-16.2 % scaffolds with near infrared laser irradiation was about 10.5 % and 9.9 %, respectively. At the same time, the prepared composite hydrogel scaffolds possessed satisfactory biocompatibility and could support the adhesion and spread of rabbit bone mesenchymal stem cells (rBMSCs) and rabbit chondrocytes in the hydrogel scaffolds, and further promoted the formation of new bone and cartilage tissue in vivo, on account of the stimulation effect of released bioactive ions. Therefore, the prepared composite hydrogel scaffolds is expected to provide a new therapeutic strategy for the postoperative adjuvant treatment of chondrosarcoma.

A one-step polyphenol-based functionalization strategy of dual-enhanced antibacterial and osteogenic surfaces

Infected bone defect is a critical problem in clinical practice of orthopedics. To solve this problem, implants with dual-functional surfaces which possess both antibacterial and osteogenic properties have extensive applications. However, there remains a pressing need to develop a convenient strategy for preparing such surfaces facilely. In this study, we reported a novel one-step polyphenol-based surface functionalization strategy for preparing two fibrous membranes with antibacterial and osteogenic capabilities. The formation of RGD-HHC36 (RH) or RGD-polyhexamethylene guanidine (RP) coating was fabricated by Michael reaction with poly (tannic acid) (PTA) to produce dual-functional fibrous membranes (PLA-RH and PLA-RP, respectively). The surfaces of PLA-RH and PLA-RP exhibited increased roughness and hydrophilicity. In vitro tests revealed that PLA-RH and PLA-RP could eradicate over 99% of clinically common pathogenic bacteria while exhibiting significant improvements in the adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, RNA-Seq analysis revealed that the up-regulation of Chrdl1 played a key role in promoting ossification through activation of the CHRDL1-BMP4 pathway. The favourable in vivo anti-infection and osteogenesis-promoting performances were demonstrated in an infected bone defect model. PLA-RH and PLA-RP inhibited bacterial infection in the early stage, and enhanced osteogenesis in the late stage. This study provides a facile and universal strategy for designing and fabricating dual-functional surfaces for antibacterial application and tissue regeneration simultaneously.

Electrospun polycaprolactone/graphene oxide scaffolds with secondary surface porosity and gelatin-coating

Polycaprolactone (PCL) is a versatile and biodegradable synthetic polymer widely used in tissue regeneration applications owing to its versatility and mechanical properties. In this study, we employed a three-level strategy to develop innovative PCL-based scaffold biomaterials using electrospinning. First, we incorporated graphene oxide (GO); second, we introduced secondary surface porosity (SSP) through non-solvent induced phase separation (NIPS) with a diameter of approximately 2 μm; and third, we applied a gelatin coating (Gt). The inclusion of GO resulted in both a reduction in fiber size and a decrease in the size of the secondary surface pores formed on the fibers. Additionally, the incorporation of GO led to a noteworthy 20-fold increase in gelatin adhesion compared to pure SSP-PCL scaffolds. However, the mechanical properties of the gelatin-coated scaffolds exhibited a decrease compared to the uncoated scaffolds. This reduction is primarily attributed to the decrease in crystallinity in coating gelatin scaffold. Furthermore, GO and gelatin played critical roles in enhancing biodegradation and bioactivity, promoting hydroxyapatite formation on the surface of SSP-PCL scaffolds. In vitro cell viability tests demonstrated the cytocompatibility of PCL, PCL/Gt, and PCL/Gt/GO electrospun SSP scaffolds, facilitating the adhesion of human mesenchymal stem cells. Our study introduces an innovative strategy for fabricating PCL scaffolds through electrospinning, incorporating SSP for improved gelatin adsorption, and holds great promise for tissue engineering applications.

Strontium/Silicon/Calcium-Releasing Hierarchically Structured 3D-Printed Scaffolds Accelerate Osteochondral Defect Repair.

Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self-healing capacity and damaging bone structures. To tackle this problem, a scaffold-mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε-caprolactone) and strontium (Sr)-doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn-embedded scaffolds (SrBGn-µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation-related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow-derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn-µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.

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.