Recruitment Of Stem Cells Research Articles

H3K18 lactylation-mediated VCAM1 expression promotes gastric cancer progression and metastasis via AKT-mTOR-CXCL1 axis

The role of the Immunoglobulin Superfamily (IgSF) as adhesion molecules in orchestrating inflammation is pivotal, yet its specific involvement in gastric cancer (GC) remains unknown. We analyzed IgSF components and discerned conspicuously elevated VCAM1 expression in GC, correlating with a poor prognosis. Remarkably, VCAM1 enhances GC cell proliferation and migration by activating AKT-mTOR signaling. Moreover, lactate in the tumor microenvironment (TME) promotes dynamic lactylation of H3K18 (H3K18la), leading to transcriptional activation of VCAM1 in GC cells. Furthermore, VCAM1 actively mediates intercellular communication in the TME. AKT-mTOR-mediated CXCL1 expression is increased by VCAM1, facilitating the recruitment of human GC-derived mesenchymal stem cells (hGC-MSCs), thereby fostering immunesuppression and accelerating cancer progression. In summary, H3K18 lactylation upregulated VCAM1 transcription, which activated AKT-mTOR signaling, and promoted tumor cell proliferation, EMT Transition and tumor metastasis. VCAM1 upregulated CXCL1 expression by AKT-mTOR pathway, so as to facilitate hGC-MSCs and M2 macrophage recruitment and infiltration. These findings provide novel therapeutic targets for GC.

Multifunctional inverse opal microcarriers‐based cytokines delivery system with stem cell homing capability for osteoarthritis treatment

AbstractOsteoarthritis has been regarded as a complex and serious degenerative disease. Attempts in this area are focused on improving the curative effect of stem cell‐based therapies. In this work, we present a novel inverse opal microcarriers‐based cytokines delivery system to induce autologous stem cell homing for osteoarthritis treatment. Considering their important role in stem cell recruitment and chondrogenic differentiation respectively, platelet‐derived growth factor BB (PDGF‐BB) and transforming growth factor β3 (TGF‐β3) are loaded into inverse opal microcarriers as model cytokines. Since cytokine release induces the corresponding variations in characteristic reflection spectra and structural colors, the inverse opal microcarriers possess the optical self‐reporting capacity to monitor the release process. In vitro cell experiments reveal that inverse opal microcarriers could successfully recruit the gathering of mesenchymal stem cells through the release of loaded cytokines. Based on these features, we have demonstrated the enhanced therapeutic effect of PDGF‐BB and TGF‐β3 loaded inverse opal microcarriers in the treatment of rat osteoarthritis models. These results indicate that the multifunctional inverse opal microcarriers‐based cytokines delivery system would find broad prospects in osteoarthritis treatment and other biomedical fields.

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.

Apt‐19s‐Functionalized 3D‐Printed Mesoporous Bioactive Glass Scaffold Promotes BMSC Recruitment in Bone Regeneration via SDF‐1α/CXCR4 Axis and MAPK Signaling

AbstractDirectional migration and differentiation of stem cells in situ are two essential processes for tissue regeneration. However, transplanted scaffold itself lacks sufficient ability to induce stem cell recruitment. As an artificial synthesized nucleic acid, aptamer 19s (Apt‐19s), with high cost‐effectiveness and bioactivity, demonstrates a robust capacity for specific binding and recruitment of mesenchymal stem cells. In this study, a mesoporous bioactive glass scaffold fabricated via a seamless route of self‐assembly and 3D printing (3D‐MBG), functionalized with Apt‐19s is successfully prepared via physical adsorption and lyophilization with optimized release kinetics and bone marrow‐derived mesenchymal stem cells (BMSCs) recruiting efficiency in vitro. This scaffold significantly enhanced migration and osteogenic differentiation of BMSCs in vitro and in vivo. The mechanism underlying Apt‐19s‐induced BMSCs recruitment is elucidated for the first time, that Apt‐19s promoted BMSCs migration by upregulating stromal cell‐derived factor‐1α (SDF‐1α) gene expression, facilitating SDF‐1α protein translation and secretion, and further activating the SDF‐1α/CXCR4 signaling axis and MAPK pathway. In summary, the Apt‐19s‐functionalized 3D‐MBG scaffold offers an economical and efficient solution for customized bone regeneration in situ, and the elucidation of Apt‐19s‐induced BMSCs recruitment at molecular biological level may shed light on its broader clinical applications.

3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration

Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.

Janus Membrane with Intrafibrillarly Strontium-Apatite-Mineralized Collagen for Guided Bone Regeneration.

Commercial collagen membranes face difficulty in guided bone regeneration (GBR) due to the absence of hierarchical structural design, effective interface management, and diverse bioactivity. Herein, a Janus membrane called SrJM is developed that consists of a porous collagen face to enhance osteogenic function and a dense face to maintain barrier function. Specifically, biomimetic intrafibrillar mineralization of collagen with strontium apatite is realized by liquid precursors of amorphous strontium phosphate. Polycaprolactone methacryloyl is further integrated on one side of the collagen as a dense face, which endows SrJM with mechanical support and a prolonged lifespan. In vitro experiments demonstrate that the dense face of SrJM acts as a strong barrier against fibroblasts, while the porous face significantly promotes cell adhesion and osteogenic differentiation through activation of calcium-sensitive receptor/integrin/Wnt signaling pathways. Meanwhile, SrJM effectively enhances osteogenesis and angiogenesis by recruiting stem cells and modulating osteoimmune response, thus creating an ideal microenvironment for bone regeneration. In vivo studies verify that the bone defect region guided by SrJM is completely repaired by newly formed vascularized bone. Overall, the outstanding performance of SrJM supports its ongoing development as a multifunctional GBR membrane, and this study provides a versatile strategy of fabricating collagen-based biomaterials for hard tissue regeneration.

Strontium-Containing Piezoelectric Biofilm Promotes Dentin Tissue Regeneration.

It remains an obstacle to induce the regeneration of hard dentin tissue in clinical settings. To overcome this, a P(VDF-TrFE) piezoelectric film with 2 wt% SrCl2 addition is designed. The biofilm shows a high flexibility, a harmonious biocompatibility, and a large piezoelectric d33 coefficient of 14 pC N-1, all contributing to building an electric microenvironment that favor the recruitment of dental pulp stem cells (DPSCs) and their differentiation into odontoblasts during normal chewing, speaking, etc. On the other hand, the strontium ions can be gradually released from the film, thus promoting DPSC odonto-differentiation. In vivo experiments also demonstrate that the film induces the release of dentin minerals and regeneration of dentin tissue. In the large animal dentin defect models, this piezoelectric film induces in situ dentin tissue formation effectively over a period of three months. This study illustrates a therapeutic potential of the piezoelectric film to improve dentin tissue repair in clinical settings.

Engineered Microchannel Scaffolds with Instructive Niches Reinforce Endogenous Bone Regeneration by Regulating CSF-1/CSF-1R Pathway.

Structural and physiological cues provide guidance for the directional migration and spatial organization of endogenous cells. Here, a microchannel scaffold with instructive niches is developed using a circumferential freeze-casting technique with an alkaline salting-out strategy. Thereinto, polydopamine-coated nano-hydroxyapatite is employed as a functional inorganic linker to participate in the entanglement and crystallization of chitosan molecules. This scaffold orchestrates the advantage of an oriented porous structure for rapid cell infiltration and satisfactory immunomodulatory capacity to promote stem cell recruitment, retention, and subsequent osteogenic differentiation. Transcriptomic analysis as well as its in vitro and in vivo verification demonstrates that essential colony-stimulating factor-1 (CSF-1) factor is induced by this scaffold, and effectively bound to the target colony-stimulating factor-1 receptor (CSF-1R) on the macrophage surface to activate the M2 phenotype, achieving substantial endogenous bone regeneration. This strategy provides a simple and efficient approach for engineering inducible bone regenerative biomaterials.

Biodegradable Nanoflowers with Abaloparatide Spatiotemporal Management of Functional Alveolar Bone Regeneration.

Post-extraction alveolar bone atrophy greatly hinders the subsequent orthodontic tooth movement (OTM) or implant placement. In this study, we synthesized biodegradable bifunctional bioactive calcium phosphorus nanoflowers (NFs) loaded with abaloparatide (ABL), namely ABL@NFs, to achieve spatiotemporal management for alveolar bone regeneration. The NFs exhibited a porous hierarchical structure, high drug encapsulation efficacy, and desirable biocompatibility. ABL was initially released to recruit stem cells, followed by sustained release of Ca2+ and PO43- for in situ interface mineralization, establishing an osteogenic "biomineralized environment". ABL@NFs successfully restored morphologically and functionally active alveolar bone without affecting OTM. In conclusion, the ABL@NFs demonstrated promising outcomes for bone regeneration under orthodontic condition, which might provide a desirable reference of man-made "bone powder" in the hard tissue regeneration field.

Engineering a Hybrid Ti6Al4V-Based System for Responsive and Consistent Osteogenesis.

As the aging population increases worldwide, the incidence of musculoskeletal diseases and the need for orthopedic implants also arise. One of the most desirable goals in orthopedic reconstructive therapies is de novo bone formation. Yet, reproducible, long-lasting, and cost-effective strategies for implants that strongly induce osteogenesis are still in need. Nanoengineered titanium substrates (and their alloys) are among the most used materials in orthopedic implants. Although having high biocompatibility, titanium alloys hold a low bioactivity profile. The osteogenic capacity and osseointegration of Ti-based implantable systems are limited, as they critically depend on the body-substrate interactions defined by blood proteins adsorbed into implant surfaces that ultimately lead to the recruitment, proliferation, and differentiation of mesenchymal stem cells (MSCs) to comply bone formation and regeneration. In this work, a hybrid Ti6Al4V system combining micro- and nanoscale modifications induced by hydrothermal treatment followed by functionalization with a bioactive compound (fibronectin derived from human plasma) is proposed, aiming for bioactivity improvement. An evaluation of the biological activity and cellular responses in vitro with respect to bone regeneration indicated that the integration of morphological and chemical modifications into Ti6Al4V surfaces induces the osteogenic differentiation of MSCs to improve bone regeneration by an enhancement of mineral matrix formation that accelerates the osseointegration process. Overall, this hybrid system has numerous competitive advantages over more complex treatments, including reproducibility, low production cost, and potential for improved long-term maintenance of the implant.

Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.

The Added Value of a Collagenated Thermosensitive Bone Substitute as a Scaffold for Bone Regeneration.

A pre-hydrated thermosensitive collagenated biomaterial which sets at body temperature and maintains the space of the missing alveolar bone volume, OsteoBiol GTO® (GTO), has been released as a bone substitute. This study was designed to check its angiogenic and osteogenic potentials compared to OsteoBiol Gen-Os® (Gen-Os) and Geistlich Bio-Oss® (Bio-Oss). Samples of materials were incubated in culture media to obtain the extracts. Collagen release was measured in the extracts, which were used to investigate human periodontal ligament (hPDL) cell proliferation (MTT), colonization (Scratch assays) and growth factor release (ELISA). The effects on endothelial cell proliferation (MTT) and organization (Matrigel® assays) were also studied. Finally, endothelial and mesenchymal Stem Cell (hMSC) recruitment (Boyden Chambers) were investigated, and hMSC Alkaline Phosphatase (ALP) activity was measured. A higher collagen concentration was found in GTO extract, which led to significantly higher hPDL cell proliferation/colonization. All materials increased VEGF/FGF-2 growth factor secretion, endothelial cell recruitment, proliferation, and organization, but the increase was highest with GTO. All materials increased hMSC recruitment and ALP activity. However, the increase was highest with collagenated GTO and Gen-Os, which enhanced C5a and BMP-2 secretion. Overall, GTO has higher angiogenic/osteogenic potentials than the collagenated Gen-Os and the anorganic Bio-Oss. It provides a suitable scaffold for endothelial and mesenchymal stem cell recruitment, which represent essential bone regeneration requirements.

Polysaccharide hybrid scaffold encapsulated endogenous factors for microfracture enhancement by sustainable release and cell recruitment

Autologous matrix-induced chondrogenesis improves microfracture (MF), but the lack of functional cells and factors inhibit a curative effect. Here, inspired by the healing process of wounds, we prepared a polysaccharide hybrid scaffold (HDCP) to immobilize endogenous growth factors (eGFs), which were derived from platelet-rich plasma (PRP). Compared with the absence of PRP, the hybrid cross-linking network endowed this scaffold with a denser pore structure, enhanced mechanical properties, and slower protein mass transfer rate, thus ensuring the long-term sustainable release of eGFs. In vitro studies confirmed that HDCP promoted bone marrow mesenchymal stem cell recruitment, proliferation, and chondrogenic differentiation. In vivo implantation indicated that HDCP regenerated a smooth articular cartilage surface with a regular fibrous matrix arrangement structure, and the mechanical strength of the regenerated cartilage considerably improved. The obvious MF enhancement implied that PRP and polysaccharide scaffold hybridization could be used as an implantable matrix for cartilage repair.

Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche

Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low leukemic infiltration of the BM. In particular, we observe interferon gamma (IFN-γ) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EVAML) are sufficient to trigger this inflammatory HSPC response, both in vitro and in vivo. Altogether, our studies indicate that HSPCs are an unrecognized component of the inflammatory adaptation of the BM by leukemic cells. The pro-inflammatory conversion and long-lived presence of HSPCs in the BM along with their regenerative re-expansion during remission may impact clonal selection and disease evolution.

Innovative approaches in regenerative endodontics

Background: Biomimicry or biomimetics refers to developing materials and techniques inspired by natural systems. In dentistry, this approach aims to replicate natural tooth structures and functions, addressing limitations of conventional materials and techniques. Regenerative endodontics, including cell homing and revascularization, represents significant advancements in this field, focusing on pulp-dentin regeneration and tooth vitality restoration. Aim: This review explores innovative biomimetic approaches in regenerative endodontics, including the latest techniques and their clinical implications. It aims to assess the effectiveness and future prospects of these methods in enhancing tooth repair and regeneration. Methods: The review synthesizes current literature on regenerative endodontic procedures, including cell homing, revascularization, scaffold implantation, and gene therapy. It examines experimental studies, clinical trials, and advancements in biomimetic materials and techniques, highlighting their applications and outcomes. Results: The review finds that regenerative endodontics has evolved from traditional apexification to advanced techniques such as cell homing and revascularization. Cell homing, which leverages the body’s natural healing processes without cell transplantation, shows promise in generating pulp-dentin tissue. Revascularization, involving the induction of a blood clot and stem cell recruitment, has demonstrated potential in restoring vitality to necrotic teeth.

ZO-1 regulates the migration of mesenchymal stem cells in cooperation with α-catenin in response to breast tumor cells

sMesenchymal stem cells are recruited from the bone marrow into breast tumors, contributing to the creation of a tumor microenvironment that fosters tropism for breast tumors. However, the intrinsic mechanisms underlying the recruitment of bone marrow-derived mesenchymal stem cells (MSCs) into the breast tumor microenvironment are still under investigation. Our discoveries identified zonula occludens-1 (ZO-1) as a specific intrinsic molecule that plays a vital role in mediating the collective migration of MSCs towards breast tumor cells and transforming growth factor beta (TGF-β), which is a crucial factor secreted by breast tumor cells. Upon migration in response to MDA-MB-231 cells and TGF-β, MSCs showed increased formation of adherens junction-like structures (AJs) expressing N-cadherin and α-catenin at their cell-cell contacts. ZO-1 was found to be recruited into the AJs at the cell-cell contacts between MSCs. Additionally, ZO-1 collaborated with α-catenin to regulate AJ formation, dependently on the SH3 and GUK domains of the ZO-1 protein. ZO-1 knockdown led to the impaired migration of MSCs in response to the stimuli and subsequent downregulation of AJs formation at the cell-cell contacts during MSCs migration. Overall, our study highlights the novel role of ZO-1 in guiding MSC migration towards breast tumor cells, suggesting its potential as a new strategy for controlling and re-engineering the breast tumor microenvironment.

Regulatory effects of stress release from decellularized periosteum on proliferation, migration, and osteogenic differentiation of periosteum-derived cells.

Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the biological effects of periosteal prestress release on periosteum-derived cells (PDCs) and the potential mechanisms of endogenous stem cell recruitment. Decellularized periosteum with natural extracellular matrix (ECM) components was obtained by a combination of physical, chemical, and enzymatic decellularization. The decellularized periosteum removed immunogenicity while retaining the natural network structure and composition of the ECM. The Young's modulus has no significant difference between the periosteum before and after decellularization. The extracted PDCs were further composited with the decellularized periosteum and subjected to 20% stress release. It was found that the proliferative capacity of PDCs seeded on decellularized periosteum was significantly enhanced 6 h after stress release of the periosteum. The cell culture supernatant obtained after periosteal prestress release was able to significantly promote the migration ability of PDCs within 24 h. Enzyme-linked immunosorbnent assay (ELISA) experiments showed that the expression of stroma-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in the supernatant increased significantly after 3 h and 12 h of stress release, respectively. Furthermore, periosteal stress release promoted the high expression of osteogenic markers osteocalcin (OCN), osteopontin (OPN), and collagen type I of PDCs. The change in stress environment caused by the release of periosteal prestress was sensed by integrin β1, a mechanoreceptor on the membrane of PDCs, which further stimulated the expression of YAP in the nucleus. These investigations provided a novel method to evaluate the importance of mechanical stimulation in periosteum, which is also of great significance for the design and fabrication of artificial periosteum with mechanical regulation function.

Bioinspired soft-hard combined system with mild photothermal therapeutic activity promotes diabetic bone defect healing via synergetic effects of immune activation and angiogenesis.

Background: The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced bone homeostasis. Thus, an advanced multifunctional therapeutic platform capable of simultaneously achieving immune regulation, bacterial elimination, and tissue regeneration is urgently designed for augmented bone regeneration under diabetic pathological milieu. Methods and Results: Herein, a photoactivated soft-hard combined scaffold system (PGCZ) was engineered by introducing polydopamine-modified zeolitic imidazolate framework-8-loaded double-network hydrogel (soft matrix component) into 3D-printed poly(ε-caprolactone) (PCL) scaffold (hard matrix component). The versatile PGCZ scaffold based on double-network hydrogel and 3D-printed PCL was thus prepared and features highly extracellular matrix-mimicking microstructure, suitable biodegradability and mechanical properties, and excellent photothermal performance, allowing long-term structural stability and mechanical support for bone regeneration. Under periodic near-infrared (NIR) irradiation, the localized photothermal effect of PGCZ triggers the on-demand release of Zn2+, which, together with repeated mild hyperthermia, collectively accelerates the proliferation and osteogenic differentiation of preosteoblasts and potently inhibits bacterial growth and biofilm formation. Additionally, the photoactivated PGCZ system also presents outstanding immunomodulatory and ROS scavenging capacities, which regulate M2 polarization of macrophages and drive functional cytokine secretion, thus leading to a pro-regenerative microenvironment in situ with enhanced vascularization. In vivo experiments further demonstrated that the PGCZ platform in conjunction with mild photothermal therapeutic activity remarkably attenuated the local inflammatory cascade, initiated endogenous stem cell recruitment and neovascularization, and orchestrated the osteoblast/osteoclast balance, ultimately accelerating diabetic bone regeneration. Conclusions: This work highlights the potential application of a photoactivated soft-hard combined system that provides long-term biophysical (mild photothermal stimulation) and biochemical (on-demand ion delivery) cues for accelerated healing of diabetic bone defects.

Revascularization in Immature Permanent Teeth - A Case Series

Immature permanent teeth with developing, root apices with dental pulp infections resulting from caries or trauma represent a formidable clinical challenge. Biologically based principles of regenerative endodontic procedures in the treatment of immature, necrotic teeth have replaced the traditional ‘apexification’ procedures. The purpose of this case series was to investigate the outcome of the pulpal revascularization procedure on immature permanent teeth with or without apical periodontitis. The case series comprised 3 patients (8–11 years of age), consisting of 4 incisors and 1 premolar with incompletely formed apex with or without signs or symptoms of periapical pathology. Induction of blood clot was the technique selected for root closure if the tooth was asymptomatic following the placement of intracanal antibiotic paste for 3 weeks. Apexification was initiated if the tooth remains symptomatic. Out of the five teeth revascularisation was successful, and continued root-end closure was obtained in four teeth. One tooth remained symptomatic and apexification was initiated. One patient failed to follow up for the study. Revascularisation by induction of apical bleeding is a potential source of stem cells for the continued root maturation and it creates a blood clot that would act as a biologic scaffold for the recruited stem cells.

Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells

Stem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models. We find that BP@SDF1-α can efficiently recruit exogenous SCs and endogenous S/PCs to corpus cavernosum and main pelvic ganglion (MPG) by local administration. Of note, ascribing to endogenous S/PCs recruitment, it also successfully alleviates ED in BCNI rat models by enhancing the protein expression levels of α-SMA, CD31, and nNOs, and eliciting less collagen deposition in the penis after its combined injection at corpus cavernosum and MPG. Thus, this study provides a new insight into the treatment of ED with endogenous S/PCs.Biodegradable Nano Black Phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve Injury Rat Model by recruiting endogenous Stem/Progenitor cells