Gelatin Enhances the Wet Mechanical Properties of Poly(D,L-Lactic Acid) Membranes.

Biodegradable (BP) poly(D,L-lactic acid) (PDLLA) membranes are widely used in tissue engineering. Here, we investigate the effects of varying concentrations of PDLLA/gelatin membranes electrospun in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP; C3H2F6O) solvent on their mechanical and physical properties as well as their biocompatibility. Regardless of the environmental conditions, increasing the gelatin content resulted in elevated stress and reduced strain at membrane failure. There was a remarkable difference in strain-to-failure between dry and wet PDLLA/gelatin membranes, with wet strains consistently higher than those of the dry membranes because of the hydrophilic nature of gelatin. A similar wet strain (εw = 2.7-3.0) was observed in PDLLA/gelatin membranes with a gelatin content between 10 and 40%. Both dry and wet stresses increased with increasing gelatin content. The dry stress on PDLLA/gelatin membranes (σd = 6.7-9.7 MPa) consistently exceeded the wet stress (σw = 4.5-8.6 MPa). The water uptake capacity (WUC) improved, increasing from 57% to 624% with the addition of 40% gelatin to PDLLA. PDLLA/gelatin hybrid membranes containing 10 to 20 wt% gelatin exhibited favorable wet mechanical properties (σw = 5.4-6.3 MPa; εw = 2.9-3.0); WUC (337-571%), degradability (11.4-20.2%), and excellent biocompatibility.

Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.

Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (P < 0.05). These key genera were correlated with BV/TV and BV (P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.

Cationic Biopolymeric Scaffold of Chelating Nanohydroxyapatite Self-Regulates Intraoral Microenvironment for Periodontal Bone Regeneration.

Periodontal bone defect is a common but longstanding healthcare issue since traditional bone grafts have limited functionalities in regulating complex intraoral microenvironments. Here, a porous cationic biopolymeric scaffold (CSC-g-nHAp) with microenvironment self-regulating ability was synthesized by chitosan-catechol chelating the Ca2+ of nanohydroxyapatite and bonding type I collagen. Chitosan-catechol's inherent antibacterial and antioxidant abilities endowed this scaffold with desirable abilities to eliminate periodontal pathogen infection and maintain homeostatic balances between free radical generation and elimination. Meanwhile, this scaffold promoted rat bone marrow stromal cells' osteogenic differentiation and achieved significant ectopic mineralization after 4 weeks of subcutaneous implantation in nude mice. Moreover, after 8 weeks of implantation in the rat critical-sized periodontal bone defect model, CSC-g-nHAp conferred 5.5-fold greater alveolar bone regeneration than the untreated group. This cationic biopolymeric scaffold could regulate the local microenvironment through the synergistic effects of its antibacterial, antioxidant, and osteoconductive activities to promote solid periodontal bone regeneration.

LIPUS-S/B@NPs regulates the release of SDF-1 and BMP-2 to promote stem cell recruitment-osteogenesis for periodontal bone regeneration.

Purpose: Poly (lactic-co-glycolic acid)-based nanoparticles (PLGA NPs) have been widely used as the carrier for sustainable drug delivery. However, the drug release from the NPs was usually incomplete and uncontrollable. Herein, a low intensity pulsed ultrasound (LIPUS) assisted SDF-1/BMP-2@nanoparticles (S/B@NPs) system was fabricated to facilitate stem cell recruitment-osteogenesis for periodontal bone regeneration. Methods: In this work, S/B@NPs were prepared with double-emulsion synthesis method. Then the S/B release profile from NPs was evaluated with or without low intensity pulsed ultrasound treatment. Afterwards, the stem cell recruiting and osteoinductive capacities of LIPUS-S/B@NPs were detected with human periodontal ligament cells (hPDLCs) in vitro and in a rat periodontal bone defect model. Results: The results indicated that S/B@NPs were successfully prepared and LIPUS could effectively regulate the release of S/B and increase their final releasing amount. Moreover, LIPUS-S/B@NPs system significantly promoted hPDLCs migrating and osteogenesis in vitro and recruiting rBMSCs to the rat periodontal defect and facilitated bone regeneration in vivo. Conclusion: Our LIPUS assisted S/B@NPs system can effectively facilitate stem cell recruitment and periodontal bone regeneration. Considering its reliable safety and therapeutic effect on bone fracture, LIPUS, as an adjuvant therapy, holds great potential in the regulation of drug delivery systems for bone healing.

Bisphosphonate-Modified Functional Supramolecular Hydrogel Promotes Periodontal Bone Regeneration by Osteoclast Inhibition.

Regeneration of periodontal tissue remains a challenge. Under periodontitis, osteoclasts are overactivated and bone loss occurs. We incorporated sodium alendronate (Alen), a medication commonly used to treat osteoporosis, into a supramolecular hydrogel system in order to create a novel biomaterial that would promote periodontal bone regeneration by inhibiting osteoclast overactivation. The Nap-Gly-Phe-Phe (NapGFF) peptide chain was modified to synthesize the functional Nap-Alen gelator. Afterward, the Nap-Alen/HAP supramolecular hydrogel composite with a suitable hydroxyapatite (HAP) ratio was constructed, which has outstanding mechanical properties and 3D structure. In addition to its good biocompatibility, it can inhibit the proliferation of bone marrow-derived macrophages (BMDMs) and differentiation of osteoclasts. Due to the simultaneous introduction of porous HAP, the hydrogel with a nanofiber structure was formed into a 3D mesh-like sparse porous composite hydrogel. While enhancing the mechanical properties of the gel, the porous structure facilitated the attachment and migration of bone regeneration-related cells. Therefore, it can effectively promote the regeneration of periodontal bone. In the future, by modifying the biophysical properties and loading stem cells or cytokines, this supramolecular hydrogel composite constructed in this study may provide a new strategy for tissue regeneration engineering and provide a preliminary experimental basis for relevant clinical translational studies.

Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(dl-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell "recruitment-osteogenesis" cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simultaneously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/ß-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

A Biomimetic Smart Nanoplatform as "Inflammation Scavenger" for Regenerative Therapy of Periodontal Tissue.

Introduction: The functional reconstruction of periodontal tissue defects remains a clinical challenge due to excessive and prolonged host response to various endogenous and exogenous pro-inflammatory stimuli. Thus, a biomimetic nanoplatform with the capability of modulating inflammatory response in a microenvironment-responsive manner is attractive for regenerative therapy of periodontal tissue. Methods: Herein, a facile and green design of engineered bone graft materials was developed by integrating a biomimetic apatite nanocomposite with a smart-release coating, which could realize inflammatory modulation by "on-demand" delivery of the anti-inflammatory agent through a pH-sensing mechanism. Results: In vitro and in vivo experiments demonstrated that this biocompatible nanoplatform could facilitate the clearance of reactive oxygen species in human periodontal ligament stem cells under inflammatory conditions via inhibiting the production of endogenous proinflammatory mediators, in turn contributing to the enhanced healing efficacy of periodontal tissue. Moreover, this system exhibited effective antimicrobial activity against common pathogenic bacteria in the oral cavity, which is beneficial for the elimination of exogenous pro-inflammatory factors from bacterial infection during healing of periodontal tissue. Conclusion: The proposed strategy provides a versatile apatite nanocomposite as a promising "inflammation scavenger" and propels the development of intelligent bone graft materials for periodontal and orthopedic applications.

An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration.

BACKGROUND: The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes. RESULTS: Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration. CONCLUSIONS: Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials.

Immunomodulatory effect of dimethyloxallyl glycine/nanosilicates-loaded fibrous structure on periodontal bone remodeling.

BACKGROUND/PURPOSE: Relieving immuno-inflammatory responses is the prerequisite step for treating periodontitis. The angiogenic small molecule, dimethyloxalylglycine (DMOG), and osteoinductive inorganic nanomaterial, nanosilicate (nSi) have a powerful effect on bone regeneration, whereas the roles in osteoimmunomodulation have not been totally uncovered. Our study aimed to explore the immunomodulatory effect of DMOG/nSi-loaded fibrous membranes on periodontal bone remodeling. MATERIALS AND METHODS: The fibrous membranes were prepared by incorporating DMOG and nSi into poly (lactic-co-glycolic acid) (PLGA) with electrospinning. The morphology features, surface chemical property and biocompatibility of DMOG/nSi-PLGA fibrous membranes were characterized. Thereafter, the fibrous membranes were implanted into rat periodontal defects, bone remodeling potential and immunomodulatory effect were evaluated by micro-computed tomography (micro-CT), histological evaluation and immunohistochemical analysis. RESULTS: DMOG/nSi-PLGA membranes possessed favorable physicochemical properties and biocompatibility. After the fibrous membranes implanted into periodontal defects, DMOG/nSi-PLGA membranes could relieve immuno-inflammatory responses of the defects (reduction of inflammatory cell infiltration, CD40L and CD11b-positive cells), increased CD206-positive M2 macrophages, and eventually facilitated periodontal bone regeneration. CONCLUSION: DMOG/nSi-PLGA fibrous membranes exert protective effects during periodontal bone defect repairing, and steer immune response towards bone regeneration. Consequently, DMOG/nSi-PLGA fibrous membranes may serve as a promising scaffold in periodontal tissue engineering.

Stromal cell-derived factor-1/Exendin-4 cotherapy facilitates the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo.

OBJECTIVES: Stromal cell-derived factor-1 (SDF-1) actively directs endogenous cell homing. Exendin-4 (EX-4) promotes stem cell osteogenic differentiation. Studies revealed that EX-4 strengthened SDF-1-mediated stem cell migration. However, the effects of SDF-1 and EX-4 on periodontal ligament stem cells (PDLSCs) and bone regeneration have not been investigated. In this study, we aimed to evaluate the effects of SDF-1/EX-4 cotherapy on PDLSCs in vitro and periodontal bone regeneration in vivo. METHODS: Cell-counting kit-8 (CCK8), transwell assay, qRT-PCR and western blot were used to determine the effects and mechanism of SDF-1/EX-4 cotherapy on PDLSCs in vitro. A rat periodontal bone defect model was developed to evaluate the effects of topical application of SDF-1 and systemic injection of EX-4 on endogenous cell recruitment, osteoclastogenesis and bone regeneration in vivo. RESULTS: SDF-1/EX-4 cotherapy had additive effects on PDLSC proliferation, migration, alkaline phosphatase (ALP) activity, mineral deposition and osteogenesis-related gene expression compared to SDF-1 or EX-4 in vitro. Pretreatment with ERK inhibitor U0126 blocked SDF-1/EX-4 cotherapy induced ERK signal activation and PDLSC proliferation. SDF-1/EX-4 cotherapy significantly promoted new bone formation, recruited more CXCR4+ cells and CD90+ /CD34- stromal cells to the defects, enhanced early-stage osteoclastogenesis and osteogenesis-related markers expression in regenerated bone compared to control, SDF-1 or EX-4 in vivo. CONCLUSIONS: SDF-1/EX-4 cotherapy synergistically regulated PDLSC activities, promoted periodontal bone formation, thereby providing a new strategy for periodontal bone regeneration.

The use of TLR2 modified BMSCs for enhanced bone regeneration in the inflammatory micro-environment.

The repair of periodontal bone tissue defects in patients with periodontitis is one of the major challenges for dentists. Stem cell-based bone regeneration has been considered as a promising strategy to restore the lost periodontal bone tissue. However, the local inflammatory environment of periodontal tissue affects stem cell-based periodontal bone regeneration. Toll-like receptor 2 (TLR2), a member of the TLR family, plays an important role in regulating immunoreaction. Previous studies have shown that the activation of TLR2 signaling pathway is involved in enhancing tissue vascularization and wound healing. However, the mechanisms underlying the therapeutic effects of TLR2 on regulating bone marrow stromal cells (BMSCs) mediated periodontal bone tissue regeneration still need to be further investigated. In this study, we tested the effect of TLR2 on regulating BMSCs mediated alveolar bone regeneration by establishing a TLR2 gene-modified canine BMSCs using a lentivirus. Activation of TLR2 significantly enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and bone morphogenetic protein 2 (BMP-2) and then upregulated the expression of their downstream osteogenic and angiogenic related gene in BMSCs. TLR2-BMSCs mediated bone regeneration in canine tooth extraction sockets under an inflammatory environment demonstrated that activation of the TLR2 signaling pathway significantly stimulated BMSCs meditated angiogenesis and osteogenesis.

Sustained Release of Two Bioactive Factors from Supramolecular Hydrogel Promotes Periodontal Bone Regeneration.

Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destruction but remains challenging. In research, biomaterials are used to encapsulate stem cells or bioactive factors for periodontal bone regeneration, but, to the best of our knowledge, using a supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect areas to promote periodontal bone regeneration has not been reported. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with SDF-1 and BMP-2 to prepare a supramolecular hydrogel, SDF-1/BMP-2/NapFFY. In vitro and in vivo results indicated that these two bioactive factors were ideally, synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of periodontal bone tissues. Specifically, after the bone defect areas were treated with our SDF-1/BMP-2/NapFFY hydrogel for 8 weeks using maxillary critical-sized periodontal bone defect model rats, a superior bone regeneration rate of 56.7% bone volume fraction was achieved in these rats. We anticipate that our SDF-1/BMP-2/NapFFY hydrogel could replace bone transplantation in the clinic for the repair of periodontal bone defects and periodontally accelerated osteogenic orthodontics in the near future.

Modulating macrophage responses to promote tissue regeneration by changing the formulation of bone extracellular matrix from filler particles to gel bioscaffolds.

Extracellular matrices (ECMs) derived from native tissues/organs have been used as biomaterials for tissue engineering and regenerative medicine in a wide range of preclinical and clinical settings. The success or failure of these applications is largely contingent on the host responses to the matrices in vivo. Despite retaining their native structural and functional proteins, bone ECM-based transplants have been reported to evoke adverse immune responses in many cases; thus, optimizing the immunomodulatory properties of bone ECMs is critical for ensuring downstream regenerative outcomes. Using a simple digestion-neutralization protocol, we transformed the commonly used bone-derived filler particles into gel bioscaffolds. Instead of inducing macrophages toward proinflammatory (M1) polarization, as reported in the literature and confirmed in the present study for ECM particles, the ECM gels were found to be more likely to polarize macrophages toward regulatory/anti-inflammatory (M2) phenotypes, leading to enhanced tissue regeneration in a rat periodontal defect model. The present work demonstrates a simple, practical and economical strategy to modify the immunomodulatory properties of bone ECMs before their in vivo transplantation and hence has important implications that may facilitate the use of ECM-based bioscaffolds derived from diverse sources of tissues for regenerative purposes.

Antimicrobial photodynamic active biomaterials for periodontal regeneration.

OBJECTIVE: Biomaterials for periodontal regeneration may have insufficient mechanical and antimicrobial properties or are difficult to apply under clinical conditions. The aim of the present study was to develop a polymeric bone grafting material of suitable physical appearance and antimicrobial photodynamic activity. METHODS: Two light curable biomaterials based on urethane dimethacrylate (BioM1) and a tri-armed oligoester-urethane methacrylate (BioM2) that additionally contained a mixture of ß-tricalcium phosphate microparticles and 20wt% photosensitizer mTHPC (PS) were fabricated and analyzed by their compressive strength, flexural strength and modulus of elasticity. Cytotoxicity was observed by incubating eluates and in direct-contact to MC3T3-E1 cells. Antimicrobial activity was ascertained on Porphyromonas gingivalis and Enterococcus faecalis upon illumination with laser light (652nm, 1×100J/cm2, 2×100J/cm2). RESULTS: The compressive strength, flexural strength and elastic modulus were, respectively, 311.73MPa, 22.81MPa and 318.85MPa for BioM1+PS and 742.37MPa, 7.58MPa and 406.23MPa for BioM2+PS. Both materials did not show any cytotoxic behavior. Single laser-illumination (652nm) caused total suppression of P. gingivalis (BioM2+PS), while repeated irradiation reduced E. faecalis by 3.7 (BioM1+PS) and 3.1 (BioM2+PS) log-counts. SIGNIFICANCE: Both materials show excellent mechanical and cytocompatible properties. In addition, irradiation with 652nm induced significant bacterial suppression. The manufactured biomaterials might enable a more efficient cure of periodontal bone lesions. Due to the mechanical properties functional stability might be increased. Further, the materials are antimicrobial upon illumination with light that enables a trans-mucosal eradication of residual pathogens.

Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice.

BACKGROUND: Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model. METHODS: In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation. RESULTS: Our study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm(3)) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm(3)) (P < 0.05). The percentage of bone in the periodontium in the hDPSC injection group was 12.8 ± 4.4 %, while it was 17.4 ± 5.3 % in the hDPSC sheet group (P < 0.05). CONCLUSION: Both hDPSC injection and cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.

Local administration of stromal cell-derived factor-1 promotes stem cell recruitment and bone regeneration in a rat periodontal bone defect model.

Stromal cell-derived factor-1 (SDF-1) recruits adult stem/progenitor cells via its specific receptor, C-X-C motif receptor 4 (CXCR4), to promote heart, kidney and tendon regeneration, but little is known about the effects of SDF-1 on bone regeneration in periodontal diseases. The objective of this study was to investigate whether local administration of SDF-1 in a collagen membrane scaffold enhanced the recruitment of host stem cells and improved periodontal bone defect repair. To this end, bone defects were established on the buccal side of bilateral mandibles in Wistar rats. After application of collagen membranes loaded with SDF-1 or phosphate-buffered saline (PBS) to the defects, the effects of SDF-1 on stem cell recruitment, inflammatory cell responses, angiogenesis, osteoclastogenesis, scaffold degradation, and bone regeneration were evaluated. It showed that SDF-1 recruited host-derived mesenchymal stem cells and hematopoietic stem cells to the wound area and significantly reduced the CD11b+ inflammatory cell response. Moreover, SDF-1 increased vascular formation, induced early bone osteoclastogenesis, accelerated scaffold degradation, and promoted the quality and quantity of regenerated bone. Our results suggest that this cell-free approach by local administration of SDF-1 may be an effective strategy for development as a simple and safe technique for periodontal bone regeneration.