Osteoporotic Bone Regeneration via Plenished Biomimetic PLGA Scaffold with Sequential Release System.

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.

Human Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Neural Differentiation of Neural Progenitor Cells.

Mesenchymal stem cells (MSCs) have been adopted in various preclinical and clinical studies because of their multipotency and low immunogenicity. However, numerous obstacles relating to safety issues remain. Therefore, MSC-derived extracellular vesicles (EVs) have been recently employed. EVs are nano-sized endoplasmic reticulum particles generated and released in cells that have similar biological functions to their origin cells. EVs act as cargo for bioactive molecules such as proteins and genetic materials and facilitate tissue regeneration. EVs obtained from adipose-derived MSC (ADMSC) also have neuroprotective and neurogenesis effects. On the basis of the versatile effects of EVs, we aimed to enhance the neural differentiation ability of ADMSC-derived EVs by elucidating the neurogenic-differentiation process. ADMSC-derived EVs isolated from neurogenesis conditioned media (differentiated EVs, dEVs) increased neurogenic ability by altering innate microRNA expression and cytokine composition. Consequently, dEVs promoted neuronal differentiation of neural progenitor cells in vitro, suggesting that dEVs are a prospective candidate for EV-based neurological disorder regeneration therapy.

Adenophora triphylla var. japonica Inhibits Candida Biofilm Formation, Increases Susceptibility to Antifungal Agents and Reduces Infection.

(1) Background: Candida is the most common cause of fungal infections worldwide, but due to the limited option of antifungal therapies, alternative strategies are required. (2) Methods: Adenophora triphylla var. japonica extract was used for the biofilm formation assay using RPMI1640. The combinatorial antifungal assay, the dimorphic transition assay, and the adherence assay were done to see the influence of inhibition of biofilm formation. qRT-PCR analysis were performed to check the gene expression. (3) Results: Adenophora triphylla var. japonica extract inhibited the Candida biofilm formation. Treatment of extract increased the antifungal susceptibility of miconazole from a 37% reduction in fungal growth to 99.05%, and also dose-dependently reduced the dimorphic transition of Candida and the attachment of Candida to HaCaT cells. The extract blocked the expression of hyphal-related genes, extracellular matrix genes, Ras1-cAMP-PKA pathway genes, Cph2-Tec1 pathway gene, and MAP kinase pathway gene. (4) Conclusions: In this study, the treatment of Adenophora triphylla var. japonica extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is a good target for the development of antifungal adjuvants, and Adenophora triphylla var. japonica extract should be a good candidate for biofilm-associated fungal infections.

Enhancing Neurogenesis of Neural Stem Cells Using Homogeneous Nanohole Pattern-Modified Conductive Platform.

Biocompatible platforms, wherein cells attach and grow, are important for controlling cytoskeletal dynamics and steering stem cell functions, including differentiation. Among various components, membrane integrins play a key role in focal adhesion of cells (18-20 nm in size) and are, thus, highly sensitive to the nanotopographical features of underlying substrates. Hence, it is necessary to develop a platform/technique that can provide high flexibility in controlling nanostructure sizes. We report a platform modified with homogeneous nanohole patterns, effective in guiding neurogenesis of mouse neural stem cells (mNSCs). Sizes of nanoholes were easily generated and varied using laser interference lithography (LIL), by changing the incident angles of light interference on substrates. Among three different nanohole patterns fabricated on conductive transparent electrodes, 500 nm-sized nanoholes showed the best performance for cell adhesion and spreading, based on F-actin and lamellipodia/filopodia expression. Enhanced biocompatibility and cell adhesion of these nanohole patterns ultimately resulted in the enhanced neurogenesis of mNSCs, based on the mRNAs expression level of the mNSCs marker and several neuronal markers. Therefore, platforms modified with homogeneous nanohole patterns fabricated by LIL are promising for the precise tuning of nanostructures in tissue culture platforms and useful for controlling various differentiation lineages of stem cells.

Three-Dimensional Graphene-RGD Peptide Nanoisland Composites That Enhance the Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells.

Graphene derivatives have immense potential in stem cell research. Here, we report a three-dimensional graphene/arginine-glycine-aspartic acid (RGD) peptide nanoisland composite effective in guiding the osteogenesis of human adipose-derived mesenchymal stem cells (ADSCs). Amine-modified silica nanoparticles (SiNPs) were uniformly coated onto an indium tin oxide electrode (ITO), followed by graphene oxide (GO) encapsulation and electrochemical deposition of gold nanoparticles. A RGD-MAP-C peptide, with a triple-branched repeating RGD sequence and a terminal cysteine, was self-assembled onto the gold nanoparticles, generating the final three-dimensional graphene-RGD peptide nanoisland composite. We generated substrates with various gold nanoparticle-RGD peptide cluster densities, and found that the platform with the maximal number of clusters was most suitable for ADSC adhesion and spreading. Remarkably, the same platform was also highly efficient at guiding ADSC osteogenesis compared with other substrates, based on gene expression (alkaline phosphatase (ALP), runt-related transcription factor 2), enzyme activity (ALP), and calcium deposition. ADSCs induced to differentiate into osteoblasts showed higher calcium accumulations after 14-21 days than when grown on typical GO-SiNP complexes, suggesting that the platform can accelerate ADSC osteoblastic differentiation. The results demonstrate that a three-dimensional graphene-RGD peptide nanoisland composite can efficiently derive osteoblasts from mesenchymal stem cells.

Effects of two-dimensional materials on human mesenchymal stem cell behaviors.

Graphene, a typical two-dimensional (2D) material, is known to affect a variety of stem cell behaviors including adhesion, spreading, growth, and differentiation. Here, we report for the first time the effects of four different emerging 2D materials on human adipose-derived mesenchymal stem cells (hADMSCs). Graphene oxide (GO), molybdenum sulfide (MoS2), tungsten sulfide (WS2), and boron nitride (BN) were selected as model two-dimensional materials and were coated on cell-culture substrates by a drop-casting method. Acute toxicity was not observed with any of the four different 2D materials at a low concentration range (<5 µg/ml). Interestingly, the 2D material-modified substrates exhibited a higher cell adhesion, spreading, and proliferation when compared with a non-treated (NT) substrate. Remarkably, in the case of differentiation, the MoS2-, WS2-, and BN-modified substrates exhibited a better performance in terms of guiding the adipogenesis of hADMSCs when compared with both NT and GO-modified substrates, based on the mRNA expression level (qPCR) and amount of lipid droplets (ORO staining). In contrast, the osteogenesis was found to be most efficiently induced by the GO-coated substrate (50 µg/mL) among all 2D-material coated substrates. In summary, 2D materials could act as favorable sources for controlling the stem cell growth and differentiation, which might be highly advantageous in both biomedical research and therapy.

Multifunctional vitamin D-incorporated PLGA scaffold with BMP/VEGF-overexpressed tonsil-derived MSC via CRISPR/Cas9 for bone tissue regeneration.

Guiding endogenous regeneration of bone defects using biomaterials and regenerative medicine is considered an optimal strategy. One of the effective therapeutic approaches involves using transgene-expressed stem cells to treat tissue destruction and replace damaged parts. Among the various gene editing techniques for cells, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is considered as a promising method owing to the increasing therapeutic potential of cells by targeting specific sites. Herein, a vitamin D-incorporated poly(lactic-co-glycolic acid) (PLGA) scaffold with bone morphogenetic protein 2 (BMP2)/vascular endothelial growth factor (VEGF)-overexpressed tonsil-derived MSCs (ToMSCs) via CRISPR/Cas9 was introduced for bone tissue regeneration. The optimized seeding ratio of engineered ToMSCs on the scaffold demonstrated favorable immunomodulatory function, angiogenesis, and osteogenic activity in vitro. The multifunctional scaffold could potentially support stem cell in vivo and induce the transition from M1 to M2 macrophage with magnesium hydroxide and vitamin D. This study highlights the improved synergistic effect of a vitamin D-incorporated PLGA scaffold and a gene-edited ToMSCs for bone tissue engineering and regenerative medicine.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease.

INTRODUCTION: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging. OBJECTIVES: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds. METHODS: Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold. RESULTS: With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD. CONCLUSION: Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

Comparative analysis of LC-MS/MS and real-time PCR assays for efficient detection of potential allergenic silkworm.

The silkworm (Bombyx mori) has long been valued food and feed in East Asia for its abundant nutritional and medicinal attributes, conversely, it can elicit allergic responses in susceptible individuals. Therefore, the development of silkworm detection method is required to avert allergenic incidents. In this study, two methodologies, tandem mass spectrometry (LC-MS/MS) and real-time PCR, were developed to achieve effective silkworm detection. These methods exhibited exceptional sensitivity in identifying silkworm presence in processed foods. Furthermore, model cookies spiked with silkworm were used to validate the sensitivities of LC-MS/MS (0.0005%) and real-time PCR (0.001%). Overall, these techniques were useful for trace silkworm detection in food products; therefore, they may help prevent allergic reactions. To the best of our knowledge, this study represents the first comparison of LC-MS/MS and real-time PCR methods for silkworm detection, marking an important contribution to the field. Data are available from ProteomeXchange under identifier PXD042494.

Therapeutic potential of luteolin-loaded poly(lactic-co-glycolic acid)/modified magnesium hydroxide microsphere in functional thermosensitive hydrogel for treating neuropathic pain.

Neuropathic pain (NP) is a debilitating condition stemming from damage to the somatosensory system frequently caused by nerve injuries or lesions. While existing treatments are widely employed, they often lead to side effects and lack specificity. This study aimed to alleviate NP by developing an innovative sustained-release thermosensitive hydrogel system. The system incorporates hyaluronic acid (HA)/Pluronic F127 injectable hydrogel and bupivacaine (Bup, B) in combination with poly(lactic-co-glycolic acid; PLGA)/modified magnesium hydroxide (MH)/luteolin (Lut; PML) microspheres (PML@B/Gel). The PML@B/Gel was designed for localized and prolonged co-delivery of Bup and Lut as an anesthetic and anti-inflammatory agent, respectively. Our studies demonstrated that PML@B/Gel had exceptional biocompatibility, anti-inflammatory, and antioxidant properties. In addition, it exhibited efficient pain relief in in vitro cellular assays. Moreover, this functional hydrogel showed substantial sustained drug release while diminishing microglial activation. Consequently, it effectively mitigated mechanical allodynia and thermal hyperalgesia in in vivo rat models of chronic constriction injury (CCI). Based on our research findings, PML@B/Gel emerges as a promising therapeutic approach for the protracted treatment of NP.

Injectable Microparticle-containing hydrogel with controlled release of bioactive molecules for facial rejuvenation.

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin's components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

Hierarchical Chitin Nanocrystal-Based 3D Printed Dual-Layer Membranes Hydrogels: A Dual Drug Delivery Nano-Platform for Periodontal Tissue Regeneration.

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

Synergistic effect of Hypoxic Conditioning and Cell-Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration.

Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell-tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long-term manner. Cell-tethering colloidal hydrogels that are composed of tyramine-conjugated gelatin prevent cells from egressing through on-cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host-implant interactions. Oxygenating microparticles encapsulated in tyramine-conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic-conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti-inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC-tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.

Nature-Inspired Chiral Structures: Fabrication Methods and Multifaceted Applications.

Diverse chiral structures observed in nature find applications across various domains, including engineering, chemistry, and medicine. Particularly notable is the optical activity inherent in chiral structures, which has emerged prominently in the field of optics. This phenomenon has led to a wide range of applications, encompassing optical components, catalysts, sensors, and therapeutic interventions. This review summarizes the imitations and applications of naturally occurring chiral structures. Methods for replicating chiral architectures found in nature have evolved with specific research goals. This review primarily focuses on a top-down approach and provides a summary of recent research advancements. In the latter part of this review, we will engage in discussions regarding the diverse array of applications resulting from imitating chiral structures, from the optical activity in photonic crystals to applications spanning light-emitting devices. Furthermore, we will delve into the applications of biorecognition and therapeutic methodologies, comprehensively examining and deliberating upon the multifaceted utility of chiral structures.

Multifunctional PDO Thread Coated with Mg(OH)2/ZnO Nanoparticles and Asiaticoside for Improved Facial Lifting.

As interest in skin aesthetics increases, treatments to suppress aging are increasing. Among them, a facelift is the most effective procedure for improving wrinkles. However, side effects including inflammatory reactions occur due to the limitations of the PDO thread itself used during the procedure. In this paper, to improve the function of PDO thread, inorganic particles such as magnesium hydroxide (MH) and zinc oxide (ZO) and a biologically active agent, asiaticoside, were coated on the surface of PDO thread using ultrasonic coating technology. The coated thread exhibited excellent biocompatibility, promoted collagen synthesis, reduced inflammation, and stimulated angiogenesis in vitro and in vivo. The multifunctional PDO thread has shown promising potential for skin regeneration without inducing fibrosis. Such a practical coating system and the developed multifunctional PDO thread suggest new possibilities for developing safer and more effective materials in cosmetic and regenerative medicine to prevent aging and improve skin aesthetics.

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon.

Drug-eluting balloon (DEB) system has been widely utilized for percutaneous coronary intervention (PCI), treating atherosclerosis to overcome the limitations of cardiovascular stents. With the anti-proliferative drug, everolimus (EVL), nitric oxide (NO) plays a key bioregulator role to facilitate the angiogenesis of endothelial cells (ECs) and inhibit the cell proliferation of smooth muscle cells (SMCs) in the lesions of cardiovascular diseases. Due to the very short lifetime and limited exposure area of NO in the body, the continuous release and efficient delivery of NO must be carefully considered. In this respect, a liposome-containing disulfide bonding group was introduced as a delivery vehicle of EVL and NO with the continuous release of NO via successive reaction cycles with GSH and SNAP in the blood vessel without the need for exogenous stimulations. With a multilayer coating platform consisting of a polyvinylpyrrolidone (PVP)/EVL-laden liposome with NO (EVL-NO-Lipo)/PVP, we precluded the loss of the EVL-encapsulated liposome with NO release during the transition time and maximized the transfer rate from the surface of DEB to the tissues. The sustained release of NO was monitored using a nitric oxide analyzer (NOA), and the synergistic bioactivities of EVL and NO were proved in EC and SMC with angiogenesis and cell proliferation-related assays. From the results of hemocompatibility and ex vivo studies, the feasibility was provided for future in vivo applications of the multilayer-coated DEB system.

Nitric Oxide-Releasing Bioinspired Scaffold for Exquisite Regeneration of Osteoporotic Bone via Regulation of Homeostasis.

Osteoporotic bone regeneration is a challenging process which involves the occurrence of sophisticated interactions. Although various polymeric scaffolds have been proposed for bone repair, research on osteoporotic bone regeneration remains practically limited. In particular, achieving satisfactory bone regeneration when using osteoporotic drugs is challenging including bisphosphonates. Here, a novel nitric oxide-releasing bioinspired scaffold with bioactive agents for the exquisite regeneration of osteoporotic bone is proposed. The bone-like biomimetic poly(lactic-co-glycolic acid) scaffold is first prepared in combination with organic/inorganic ECM and magnesium hydroxide as the base implant material. Nanoparticles containing bioactive agents of zinc oxide (ZO), alendronate, and BMP2 are incorporated to the biomimetic scaffold to impart multifunctionality such as anti-inflammation, angiogenesis, anti-osteoclastogenesis, and bone regeneration. Especially, nitric oxide (NO) generated from ZO stimulates the activity of cGMP and protein kinase G; in addition, ZO downregulates the RANKL/osteoprotegerin ratio by suppressing the Wnt/ß-catenin signaling pathway. The new bone is formed much better in the osteoporotic rat model than in the normal model through the regulation of bone homeostasis via the scaffold. These synergistic effects suggest that such a bioinspired scaffold could be a comprehensive way to regenerate exceptionally osteoporotic bones.

Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury.

Traumatic spinal cord injury results in permanent and serious neurological impairment, but there is no effective treatment yet. Tissue engineering approaches offer great potential for the treatment of SCI, but spinal cord complexity poses great challenges. In this study, the composite scaffold consists of a hyaluronic acid-based hydrogel, decellularized brain matrix (DBM), and bioactive compounds such as polydeoxyribonucleotide (PDRN), tumor necrosis factor-α/interferon-γ primed mesenchymal stem cell-derived extracellular vesicles (TI-EVs), and human embryonic stem cell-derived neural progenitor cells (NPC). The composite scaffold showed significant effects on regenerative prosses including angiogenesis, anti-inflammation, anti-apoptosis, and neural differentiation. In addition, the composite scaffold (DBM/PDRN/TI-EV/NPC@Gel) induced an effective spinal cord regeneration in a rat spinal cord transection model. Therefore, this multimodal approach using an integrated bioactive scaffold coupled with biochemical cues from PDRN and TI-EVs could be used as an advanced tissue engineering platform for spinal cord regeneration.

Multi-modulation of immune-inflammatory response using bioactive molecule-integrated PLGA composite for spinal fusion.

Despite current developments in bone substitute technology for spinal fusion, there is a lack of adequate materials for bone regeneration in clinical applications. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commercially available, but a severe inflammatory response is a known side effect. Bone graft substitutes that enhance osteogenesis without adverse effects are needed. We developed a bioactive molecule-laden PLGA composite with multi-modulation for bone fusion. This bioresorbable composite scaffold was considered for bone tissue engineering. Among the main components, magnesium hydroxide (MH) aids in reduction of acute inflammation affecting disruption of new bone formation. Decellularized bone extracellular matrix (bECM) and demineralized bone matrix (DBM) composites were used for osteoconductive and osteoinductive activities. A bioactive molecule, polydeoxyribonucleotide (PDRN, PN), derived from trout was used for angiogenesis during bone regeneration. A nano-emulsion method that included Span 80 was used to fabricate bioactive PLGA-MH-bECM/DBM-PDRN (PME2/PN) composite to obtain a highly effective and safe scaffold. The synergistic effect provided by PME2/PN improved not only osteogenic and angiogenic gene expression for bone fusion but also improved immunosuppression and polarization of macrophages that were important for bone tissue repair, using a rat model of posterolateral spinal fusion (PLF). It thus had sufficient biocompatibility and bioactivity for spinal fusion.

Pectolinarin Inhibits the Bacterial Biofilm Formation and Thereby Reduces Bacterial Pathogenicity.

Bacterial biofilms are a growing problem as it is a major cause of nosocomial infection from urinary catheters to chronic tissue infections and provide resistance to a variety of antibiotics and the host's immune system. The effect of pectolinarin on the biofilm formation in Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Streptococcus mutans, Streptococcus sobrinus, Staphylococcus aureus, Pseudomonas aeruginosa, Cutibacterium acnes, and Porphyromonas gingivalis was studied in TSBg (tryptic soy broth supplemented with 1% glucose). Pectolinarin inhibited biofilm formation of E. faecalis (IC50 = 0.39 µg/mL), E. faecium (IC50 = 0.19 µg/mL), E. coli (IC50 = 0.25 µg/mL), S. mutans (IC50 = 1.2 µg/mL), S. sobrinus (IC50 = 1.4 µg/mL), S. aureus (IC50 = 0.39 µg/mL), P. aeruginosa (IC50 = 0.9 µg/mL), P. acnes (IC50 = 12.5 µg/mL), and P. gingivalis (IC50 = 9.0 µg/mL) without inhibiting the bacterial growth. Pectolinarin also showed increased susceptibility of antibacterial activity with commercially available antibiotics including ampicillin, vancomycin, streptomycin, and oxytetracyclin against E. faecalis and E. faecium. Finally, pectolinarin dose-dependently reduced the expression of genes including cytolysin genes (cylLS, cylR2 and cylM), quorum sensing (QS) genes (fsrB, fsrC, gelE, ebpA, ebpB, acm, scm and bps), and biofilm virulence genes (esp) of E. faecalis and E. faecium. Pectolinarin reduced the bacterial biofilm formation, activated the antibacterial susceptibility, and reduced the bacterial adherence. These results suggest that bacterial biofilm formation is a good target to develop the antibacterial agents against biofilm-related infections.