Bone-like Tissue Research Articles

Osteosarcoma with Pathological Fracture: A Rare Case Report

Introduction: Osteosarcoma is a primary malignant bone tumor originating from stem cells and is characterized by the proliferation of tumor cells that directly form immature bone or bone-like tissue. Osteosarcoma represents only 3% to 5% of all spinal malignancies. The aim of study is to discuss the importance of diagnostic investigation for a relatively rare case of spinal osteosarcoma. Case presentation: A 49 years old female came to the Emergency Unit, with a chief complaint of bilateral weakness of lower extremities for 1 year and worsening in 2 weeks. Upon examination, the initial diagnosis was mistaken for a spinal canal stenosis because metastatic bone disease from previous history of malignant melanoma. Subsequently, a decompression with stabilization fusion and biopsy is performed. Primary osteosarcoma was confirmed from histopathology results. Further chemotherapy is planned referring to confirmed primary osteosarcoma on histopathology. Discussion: Spinal osteosarcoma is very rare. Osteosarcoma occurs most frequently in the appendicular skeleton, especially the distal femur and proximal tibial metaphysis, which account for 90% of all cases. Primary osteosarcomas of the vertebral column are uncommon and occur dominantly in the vertebral body. Biopsy remains the gold standard of care for diagnosis. Conclusion: The performance of MRI and pathologic evaluation with immunohistochemistry is particularly important for the differential diagnosis of soft tissue tumors. Histopathologic analysis also plays an important role in differentiating from metastatic bone disease. An aggressive treatment plan and long-term follow-up are mandatory in managing this case. Keywords: osteosarcoma, spinal osteosarcoma, spinal canal stenosis, malignancy, pathological fracture, rare case.

GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.

To investigate the biological regulatory function of Gremlin1 (GREM1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) in dental pulp stem cells (DPSCs), and determine the underlying molecular mechanism involved. Alkaline phosphatase (ALP) activity, alizarin red staining, scratch migration assays and in vitro and in vivo osteo-/dentinogenic marker detection of bone-like tissue generation in nude mice were used to assess osteo-/dentinogenic differentiation. Coimmunoprecipitation and polypeptide microarray assays were employed to detect the molecular mechanisms involved. The data revealed that knockdown of GREM1 promoted ALP activity, mineralisation in vitro and the expression of osteo-/dentinogenic differentiation markers and enhanced osteo-/ dentinogenesis of DPSCs in vivo. GREM1 bound to YWHAH in DPSCs, and the binding site was also identified. Knockdown of YWHAH suppressed the osteo-/dentinogenesis of DPSCs in vitro, and overexpression of YWHAH promoted the osteo-/dentinogenesis of DPSCs in vitro and in vivo. Taken together, the findings highlight the critical roles of GREM1-YWHAH in the osteo-/dentinogenesis of DPSCs.

Biocompatibility Evaluation of an Artificial Metallic Bone with Lattice Structure for Reconstruction of Bone Defect.

Mandibular reconstruction for large bone defects is performed with consideration of patients' specific morphology and sufficient strength. Metal additive manufacturing techniques have been used to develop biomaterials for mandibular reconstruction. Titanium artificial mandibles with a lattice structure have been proposed, and the optimal conditions for their strength to withstand mechanical stress around the mandible have been reported. This study investigated the biocompatibility of a titanium artificial bone with a lattice structure fabricated under optimal conditions. The samples were fabricated using metal additive manufacturing. Body diagonals with nodes (BDN) were selected as suitable lattice structures. Dode medium (DM) was selected for comparison. The samples were implanted into rabbit tibial defects and resected with the surrounding bone at two and four weeks. Specimens were evaluated radiographically, histologically, and histomorphometrically. Radiopacity in each lattice structure was observed at two and four weeks. Histological evaluation showed trabecular bone-like tissue inside the BDN compared to the DM at four weeks. No significant differences were noted in the bone volume inside the structures. This study demonstrated the in vivo compatibility of artificial metallic bones with a BDN structure under mechanical stress conditions.

Histological analysis and etiology of a pathological iguanodontian femur from England.

Derived ornithopods, such as hadrosaurids, show a high occurrence of fossilized lesions and diseases. However, paleopathologies in iguanodontians seem to be less common, considering the rich fossil record of these taxa in Europe, in particular in Belgium, Britain and Spain. Here, we describe an iguanodontian femur discovered in England that exhibits a large overgrowth of its lateral aspect, not previously recognized in any other similar remains. The specimen was scanned with micro-computed tomography (microCT) and later sectioned in three sites of the overgrowth for histological analysis. The femur belongs to an early adult Iguanodontia indet., based on the presence of a woven parallel fibered complex in the outer cortex and three to four lines of arrested growth. Internal analysis of the dome-like overgrowth suggests it can be diagnosed as a fracture callus. The injury might have negatively impacted upon the animal's locomotion as the trauma had occurred in the region above the knee, a crucial spot for hindlimb musculature. Finally, a cancellous medullary bone-like tissue was recognized in the medullary cavity next to the pathological overgrowth. An attempt was made to determine the precise nature of this tissue, as medullary bone is linked with the ovulation period in (avian) dinosaurs, whereas other types of endosteal, medullary bone-like tissue have previously been recognized in pathological bones.

Predentin's influence on clastic cell behavior in human external cervical resorption: Evidence from a case study

External cervical resorption (ECR) is an aggressive disease characterized by resorption of the tooth root structure. While the pericanalar resorption-resistant sheet (PRRS) impedes ECR progression towards the pulp, the underlying mechanisms of its protective role in human teeth remain unclear. This study aimed to elucidate the pathology of ECR in a 31-year-old female patient by employing radiographic, histological, and immunohistochemical analyses of an extracted tooth. Histological examination revealed that the PRRS comprised dentin, predentin, and reparative bone-like tissue. Notably, clastic cells were observed on the surfaces of all three tissues within the same specimens. Immunohistochemical staining for cathepsin K demonstrated diminished resorptive activity of clastic cells on predentin compared to dentin and bone-like tissue. These findings suggest a potential role for predentin in attenuating clastic cell activity, potentially serving as the final barrier safeguarding the pulp tissue.

A case of dedifferentiated liposarcoma discovered due to an intrascrotal calcified ossification.

Dedifferentiated liposarcoma is a rare cancer with a poor prognosis. A 52-year-old man presented with a chief complaint of a mass in his left scrotum. He came with suspected testicular tumor, but all the measured tumor markers were negative. Imaging test showed approximately 2cm diameter mass accompanied by calcification with some substantial components between the testis and epididymis. Left high testicular resection was performed. The tumor had no continuity between the testis and epididymis, and the spermatic cord transection was negative. Pathological findings showed well differentiated fatty component and a dedifferentiated component around the trabecular bone-like tissue. We observed dedifferentiated dysmorphic cells mixed with fatty droplets of unequal size. Immunostaining led to the diagnosis of dedifferentiated liposarcoma. No additional postoperative therapy was performed. The possibility of dedifferentiated liposarcoma should be kept in mind even if mass is confined to the scrotum and consisted of calcification. In the case of an intrascrotal calcified mass with malignant perspective, radical surgery is highly recommended.

Biphasic Calcium Phosphate and Activated Carbon Microparticles in a Plasma Clot for Bone Reconstruction and In Situ Drug Delivery: A Feasibility Study.

The development of bone-filling biomaterials capable of delivering in situ bone growth promoters or therapeutic agents is a key area of research. We previously developed a biomaterial constituting biphasic calcium phosphate (BCP) microparticles embedded in an autologous blood or plasma clot, which induced bone-like tissue formation in ectopic sites and mature bone formation in orthotopic sites, in small and large animals. More recently, we showed that activated carbon (AC) fiber cloth is a biocompatible material that can be used, due to its multiscale porosity, as therapeutic drug delivery system. The present work aimed first to assess the feasibility of preparing calibrated AC microparticles, and second to investigate the properties of a BCP/AC microparticle combination embedded in a plasma clot. We show here, for the first time, after subcutaneous (SC) implantation in mice, that the addition of AC microparticles to a BCP/plasma clot does not impair bone-like tissue formation and has a beneficial effect on the vascularization of the newly formed tissue. Our results also confirm, in this SC model, the ability of AC in particle form to adsorb and deliver large molecules at an implantation site. Altogether, these results demonstrate the feasibility of using this BCP/AC/plasma clot composite for bone reconstruction and drug delivery.

Gold capped mesoporous bioactive glass guides bone regeneration via BMSCs recruitment and drug adaptive release

Recruiting endogenous stem cells and achieving controlled drug release are crucial for in situ bone regeneration. However, it remains challenging to design functional platforms that can effectively recruit stem cells and deliver drugs at an appropriate dose and a time-dependent manner under specific stimulus conditions. Herein, mesoporous bioactive glass (MBG), nanoreservoirs of the simvastatin (Sim), was end-capped with E7 peptide-modified gold nanoparticles (Au-NPs). This unique design allowed for effective recruitment of endogenous stem cells and enabled the sustained release of simvastatin. The released simvastatin facilitated the osteogenic differentiation of stem cells, supporting bone-like tissue reconstruction. Meanwhile, under near-infrared light irradiation, MBG@Sim-Au-E7 exhibited adaptive degradation and sustained release of simvastatin and active ions. This capability regulated the osteogenic microenvironment, further facilitating bone regeneration. In addition, the results of in vivo experiments showed that the healing of skull defect was significantly improved by MBG@Sim-Au-E7 after NIR irradiation. These findings highlight the potential of MBG@Sim-Au-E7 as a promising approach for preparing functional bone healing materials.

Unraveling the transcriptome profile of pulsed electromagnetic field stimulation in bone regeneration using a bioreactor-based investigation platform

IntroductionHuman mesenchymal stem cells (hMSCs) sense and respond to biomechanical and biophysical stimuli, yet the involved signaling pathways are not fully identified. The clinical application of biophysical stimulation including pulsed electromagnetic field (PEMF) has gained momentum in musculoskeletal disorders and bone tissue engineering. MethodologyWe herein aim to explore the role of PEMF stimulation in bone regeneration by developing trabecular bone-like tissues, and then, culturing them under bone-like mechanical stimulation in an automated perfusion bioreactor combined with a custom-made PEMF stimulator. After selecting the optimal cell seeding and culture conditions for inspecting the effects of PEMF on hMSCs, transcriptomic studies were performed on cells cultured under direct perfusion with and without PEMF stimulation. ResultsWe were able to identify a set of signaling pathways and upstream regulators associated with PEMF stimulation and to distinguish those linked to bone regeneration. Our findings suggest that PEMF induces the immune potential of hMSCs by activating and inhibiting various immune-related pathways, such as macrophage classical activation and MSP-RON signaling in macrophages, respectively, while promoting angiogenesis and osteogenesis, which mimics the dynamic interplay of biological processes during bone healing. ConclusionsOverall, the adopted bioreactor-based investigation platform can be used to investigate the impact of PEMF stimulation on bone regeneration.

Guided Autotransplantation of an Immature Premolar to the Maxillary Incisor Region with Immediate Restoration of Esthetics: A Case Report

This case report describes the treatment of two maxillary central incisors following a traumatic injury with tooth #8 developing replacement resorption and #9 developing inflammatory root resorption. A 10-year-old girl presented complaining of pain in her maxillary central incisors. Upon clinical examination, teeth #8 and #9 were tender to percussion and palpation of the buccal soft tissues. Thermal and electrical pulpal sensitivity tests for teeth #8 and #9 were negative. An intraoral periapical radiograph revealed resorptive defects in tooth #8, which were filled with bone-like tissue, while tooth #9 had radiolucent resorptive defects along the root surface and a periapical radiolucency. A diagnosis of replacement resorption was made for tooth #8 and external inflammatory root resorption for tooth #9. Tooth #8 was treated with a multidisciplinary approach utilizing a guided template for premolar autotransplantation with an immediate veneer restoration, while tooth #9 was managed with root canal treatment using a tricalcium silicate cement to fill the canal. At the 1, 4, 8, 12, and 24-month follow-ups, the patient remained asymptomatic, and there was no radiographic evidence of root or periapical pathosis on either tooth. The root-end of the donor tooth transplanted to the #8 site continued to develop. This case report highlights successful interdisciplinary management of two forms of root resorption using modern treatment strategies that provided immediate function and esthetics to the maxillary central incisors in a young patient following trauma.

Modeling of intramembranous ossification using human pluripotent stem cell-derived paraxial mesoderm derivatives

Vertebrates form their skeletal tissues from three distinct origins (the neural crest, paraxial mesoderm, and lateral plate mesoderm) through two distinct modes of ossification (intramembranous and endochondral ossification). Since the paraxial mesoderm generates both intramembranous and endochondral bones, it is thought to give rise to both osteoprogenitors and osteo-chondroprogenitors. However, it remains unclear what directs the paraxial mesoderm-derived cells toward these different fates in distinct skeletal elements during human skeletal development. To answer this question, we need experimental systems that recapitulate paraxial mesoderm-mediated intramembranous and endochondral ossification processes. In this study, we aimed to develop a human pluripotent stem cell (hPSC)-based system that models the human intramembranous ossification process. We found that spheroid culture of the hPSC-derived paraxial mesoderm derivatives generates osteoprogenitors or osteo-chondroprogenitors depending on stimuli. The former induced intramembranous ossification, and the latter endochondral ossification, in mouse renal capsules. Transcriptional profiling supported the notion that bone signatures were enriched in the intramembranous bone-like tissues. Thus, we developed a system that recapitulates intramembranous ossification, and that enables the induction of two distinct modes of ossification by controlling the cell fate of the hPSC-derived paraxial mesoderm derivatives.

Osseointegrability of 3D-printed porous titanium alloy implant on tibial shaft bone defect in rabbit model.

Previous studies have demonstrated the ability of osseointegration of porous titanium implants in cancellous bone. Our study was designed to (i) investigate the ability of bone ingrowth into 3D-printed porous titanium alloy implant on the cortical bone of rabbits using CT-scan and histology, and (ii) to identify the consistency of the radiology information between clinical Cone Beam Computed Tomography (CBCT) and Micro Computed Tomography (μCT) in the evaluation of bone ingrowth. The porous titanium alloy implants were 3D-printed employing the Electron Beam Melting (EBM) technology with an intended pore size of 600 μm and porosity of approximately 50 percent. Each implant was inserted into tibial diaphysis in one rabbit and its pores were classified as contacting bone or non-contacting bone. Depending on the time of explantation, the rabbits were divided into two groups: group 1 consisting of 6 rabbits between 13 and 20 weeks and group 2 consisting of 6 rabbits between 26 and 32 weeks. Tissue ingrowth into the non-bone contacting pores were evaluated by CBCT and histology. μCT was used to further investigate the bone ingrowth into four implants (two from each group were randomly chosen). The CBCT detected the present of tissue with bone-like density in both bone-contacting pores and non-bone-contacting pores of all implants. The μCT analysis also supported this result. All the bone-like tissues were then histologically confirmed to be mature bone. The analysis of CBCT data to assess bone ingrowth in porous implants had the sensitivity, specificity, positive and negative predictive values of 85, 84, 93 and 70 percent, respectively, when considering μCT assessment as the gold standard. Fully porous titanium alloy implant has great potential to reconstruct diaphyseal bone defect due to its good ability of osseointegration. CBCT is a promising method for evaluation of bone ingrowth into porous implants.

Ant-nest type porous scaffold with micro-struts consisting of carbonate apatite for promoting bone formation and scaffold resorption.

Scaffolds having appropriate mechanical strength and providing a proper microenvironment for osteogenesis are expected to be effective alternatives to autografts for bone regeneration. In this study, ant-nest type porous (ANP) scaffolds consisting of CO3 Ap were fabricated using calcium carbonate powder or slurry and two types of polyurethane foam through a dissolution-precipitation reaction. ANP-type, three-dimensional, interconnected porous CO3 Ap scaffolds were fabricated by burning out the struts of polyurethane foams embedded in CaCO3 , followed by compositional transformation from CaCO3 to CO3 Ap. The types of polyurethane foam and impregnation methods of CaCO3 into polyurethane form affected the geometry of the resulting ANP structures. Mechanical and in vivo biological performances of these scaffolds relied on the geometry of the ANP structures. The ANP structures displayed had a clear structural advantage in bone regeneration, owing to the promotion of cell and tissue migration throughout the scaffolds. In particular, ANP-structured scaffolds, which had highest porosity, interconnectivity, and smallest strut thickness, had a mechanical strength comparable to cancellous bone, formed more new bone, were highly resorbed, resulting in cancellous bone-like bone tissue regeneration at 12 weeks of healing. The results suggest that bone regeneration after the migration of cell and tissue into the entire scaffolds is affected by strut thickness preferentially over porosity and interconnectivity. ANP-structured CO3 Ap scaffolds are attractive for bone regeneration.

A Novel Bioimplant Comprising Ad-BMP9-Transfected BMSCs and GelMA Microspheres Produced from Microfluidic Devices for Bone Tissue Engineering

Oral and maxillofacial bone defect repair in patients remains challenging in clinical treatment due to the different morphologies of bone defects. An injectable hydrogel of microspheres with sustained bone morphogenetic protein 9 (BMP9) expression for oral and maxillofacial bone defect repair has been developed. This study is bioinspired by the substantial osteogenesis property of recombinant adenoviruses expressing bone morphogenetic protein 9 (Ad-BMP9) and minimally invasive treatment by injection. A novel scaffold encompassing bone mesenchymal stem cells (BMSCs) transfected with Ad-BMP9 was produced and cocultured on a superficial surface of monodisperse photocrosslinked methacrylate gelatin hydrogel microspheres (GelMA/MS, produced with microfluidic technology). The biological tests including live/dead cell staining, phalloidin staining, cell counting kit-8 (CCK-8) assay, alkaline phosphatase (ALP) activity and staining, alizarin red S staining, and quantitative real-time polymerase chain reaction (RT-qPCR), revealed that the hydrogel microspheres exhibited good biocompatibility and remarkably promoted the osteogenic differentiation of BMSCs in vitro. In addition, a small needle was injected the innovative scaffold beneath the nude mice’s skin. The micro-CT and histological staining assay results demonstrated that the new implant, with high blood vessel formation markers (CD31-positive cells) expression over four and eight weeks, achieved significant vascularized bone-like tissue formation. Consequently, the injectable hydrogel microspheres, cocultured with BMSC transfected with Ad-BMP9, enhanced vascularized bone regeneration, therefore representing a facile and promising technique for the minimally invasive treatment of oral and maxillofacial bone defects.

Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture

Healthy bone is maintained by the process of bone remodeling. An unbalance in this process can lead to pathologies such as osteoporosis which are often studied with animal models. However, data from animals have limited power in predicting the results that will be obtained in human clinical trials. In search for alternatives to animal models, human in vitro models are emerging as they address the principle of reduction, refinement, and replacement of animal experiments (3Rs). At the moment, no complete in vitro model for bone-remodeling exists. Microfluidic chips offer great possibilities, particularly because of the dynamic culture options, which are crucial for in vitro bone formation. In this study, a scaffold free, fully human, 3D microfluidic coculture model of bone remodeling is presented. A bone-on-a-chip coculture system was developed in which human mesenchymal stromal cells differentiated into the osteoblastic lineage and self-assembled into scaffold free bone-like tissues with the shape and dimensions of human trabeculae. Human monocytes were able to attach to these tissues and to fuse into multinucleated osteoclast-like cells, establishing the coculture. Computational modeling was used to determine the fluid flow induced shear stress and strain in the formed tissue. Furthermore, a set-up was developed allowing for long-term (35 days) on-chip cell culture with benefits including continuous fluid-flow, low bubble formation risk, easy culture medium exchange inside the incubator and live cell imaging options. This on-chip coculture is a crucial advance towards developing in vitro bone remodeling models to facilitate drug testing.

Spatiotemporal and microstructural characterization of heterotopic ossification in healing rat Achilles tendons.

Achilles tendon rupture is a common debilitating medical condition. The healing process is slow and can be affected by heterotopic ossification (HO), which occurs when pathologic bone-like tissue is deposited instead of the soft collagenous tendon tissue. Little is known about the temporal and spatial progression of HO during Achilles tendon healing. In this study we characterize HO deposition, microstructure, and location at different stages of healing in a rat model. We use phase contrast-enhanced synchrotron microtomography, a state-of-the-art technique that allows 3D imaging at high-resolution of soft biological tissues without invasive or time-consuming sample preparation. The results increase our understanding of HO deposition, from the early inflammatory phase of tendon healing, by showing that the deposition is initiated as early as one week after injury in the distal stump and mostly growing on preinjury HO deposits. Later, more deposits form first in the stumps and then all over the tendon callus, merging into large, calcified structures, which occupy up to 10% of the tendon volume. The HOs were characterized by a looser connective trabecular-like structure and a proteoglycan-rich matrix containing chondrocyte-like cells with lacunae. The study shows the potential of 3D imaging at high-resolution by phase-contrast tomography to better understand ossification in healing tendons.

Characterization of three-dimensional bone-like tissue growth and organization under influence of directional fluid flow.

The transition in the field of bone tissue engineering from bone regeneration to in vitro models has come with the challenge of recreating a dense and anisotropic bone-like extracellular matrix (ECM). Although the mechanism by which bone ECM gains its structure is not fully understood, mechanical loading and curvature have been identified as potential contributors. Here, guided by computational simulations, we evaluated cell and bone-like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human mesenchymal stromal cells were seeded on donut-shaped silk fibroin scaffolds and osteogenically stimulated for 42 days statically or in a flow perfusion bioreactor. After 14, 28, and 42 days, constructs were investigated for cell and tissue growth and organization. As a result, directional fluid flow was able to improve organic tissue growth but not organization. Cells tended to orient in the tangential direction of the channel, possibly attributed to its curvature. Based on our results, we suggest that organic ECM production but not anisotropy can be stimulated through the application of fluid flow. With this study, an initial attempt in three-dimensions was made to improve the resemblance of in vitro produced bone-like ECM to the physiological bone ECM.

Engineering of an Osteoinductive and Growth Factor‐Free Injectable Bone‐Like Microgel for Bone Regeneration (Adv. Healthcare Mater. 11/2023)

Biomineralization Article 2200976 by Luiz E. Bertassoni and co-workers presents injectable cell-laden bone-like tissue constructs that show promise as minimally invasive and growth factor-free alternatives to bone autografts for repair and regeneration of critical sized bone defects. By approximating the cellular, structural, and chemical composition of native bone, the engineered microconstructs promote native-like mechanisms of osteogenesis via unique mechanotransductive and phosphate signaling pathways.

Engineering of an Osteoinductive and Growth Factor-Free Injectable Bone-Like Microgel for Bone Regeneration.

Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. Bone morphogenetic protein-loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes. This highlights the need to develop biomaterials that closely approximate the structure and composition of bone autografts, which are inherently osteoinductive and biologically active with embedded living cells, without the need for added supplements. Here, injectable growth factor-free bone-like tissue constructs are developed, that closely approximate the cellular, structural, and chemical composition of bone autografts. It is demonstrated that these micro-constructs are inherently osteogenic, and demonstrate the ability to stimulate mineralized tissue formation and regenerate bone in critical-sized defects in-vivo. Furthermore, the mechanisms that allow human mesenchymal stem cells (hMSCs) to be highly osteogenic in these constructs, despite the lack of osteoinductive supplements, are assessed, whereby Yes activated protein (YAP) nuclear localization and adenosine signaling appear to regulate osteogenic cell differentiation. The findings represent a step toward a new class of minimally invasive, injectable, and inherently osteoinductive scaffolds, which are regenerative by virtue of their ability to mimic the tissue cellular and extracellular microenvironment, thus showing promise for clinical applications in regenerative engineering.

The Role of SDF-1α-CXCR4/CXCR7 in Migration of Human Periodontal Ligament Stem Cells.

Regenerative endodontic procedures (REPs) are a research hotspot in the endodontic field. One of the biggest problems of REPs is that it is difficult to realize regeneration of pulp-dentin complex and functional reconstruction. The reason is still not clear. We hypothesize that the migration may be different in different dental stem cells. Periodontal ligament stem cells (PDLSCs) may migrate faster than stem cells of apical papilla (SCAPs), differentiating into cementum-like tissue, bone-like tissue and periodontal ligament-like tissue and, finally affecting the outcomes of REPs. Hence, this study aimed to explore the mechanism that regulates the migration of PDLSCs. After isolating and culturing PDLSCs and SCAPs from human third molars, we compared the migration of PDLSCs and SCAPs. Then we investigated the role of SDF-1α-CXCR4/CXCR7 axis in PDLSC migration. We further investigated the impact of Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) on PDLSC migration and the potential mechanism. PDLSCs showed better migration under both noninflammatory and inflammatory conditions than SCAPs. SDF-1α can promote the migration of PDLSCs by elevating the expression of CXCR4 and CXCR7, increasing the interaction between them, promoting expression of β-arrestin1 and activating the ERK signaling pathway. P. gingivalis LPS can promote the migration of PDLSCs toward SDF-1α through increasing the expression of CXCR4 via the NF-κB signaling pathway, promoting the expression of β-arrestin1, and activating the ERK signaling pathway. This study helped elucidate the potential reason for the difficulty in forming pulp-dentin complex.