Alveolar Repair Research Articles

Alveolar cleft reconstruction with vomerine bone: two surgical procedures in one step: a case series

Aim: Iliac crest (IC) is the most common source of bone for alveolar cleft repair, as it allows for harvesting a large amount of cancellous bone with a high rate of favorable outcomes. Its drawback is the donor-site morbidity. We propose a new technique for alveolar cleft grafting using vomerine bone (VB), which, through bone grafting, reconstructs the alveolus with the VB and simultaneously corrects the nasal septum deviation. Method: We performed 18 alveolar reconstructions with VB in patients with a small bony defect and septal deviation, which would benefit from septoplasty. A matched control group with IC bone grafting was selected. Panoramic X-rays were used for vertical assessment of ossification with the Bergland scale and CT scans for the evaluation of the thickness of the grafted area in the VB and IC groups and compared with an independent samples T-test. A paired T-test compared angular measurements of the septal deviation pre- and post- vomerine grafting. Results: All grafts healed uneventfully, with no complications at the donor site and respiratory function was improved. There was no statistically significant difference in ossification height between VB and IC, the alveolar thickness at the occlusal and middle third was higher with IC. Septal deviation was reduced significantly. Conclusion: Alveolar graft from VB seems to be a viable alternative to IC in patients who present with a mild bony alveolar defect in addition to septal deviation, allowing combined procedures while reducing the morbidity of the donor site.

Does Melatonin Associated with Nanostructured Calcium Phosphate Improve Alveolar Bone Repair?

Background and objectives: Calcium phosphates have been widely used as bone substitutes, but their properties are limited to osteoconduction. The association of calcium phosphates with osteoinductive bioactive molecules has been used as a strategy in regenerative medicine. Melatonin has been studied due to its cell protection and antioxidant functions, reducing osteoclastic activity and stimulating newly formed bone. This study aimed to evaluate the effect of topical application of melatonin associated with nanostructured carbonated hydroxyapatite microspheres in the alveolar bone repair of Wistar rats through histological and histomorphometric analysis. Materials and Methods: Thirty female Wistar rats (300 g) were used, divided randomly into three experimental groups (n = 10), G1: nanostructured carbonated hydroxyapatite microspheres associated with melatonin gel (CHA-M); G2: nanostructured carbonated hydroxyapatite (CHA); G3: blood clot (without alveolar filling). The animals were euthanized after 7 and 42 days of the postoperative period and processed for histological and histomorphometric evaluation. Kruskal-Wallis and Dunn's post-test were applied to investigate statistical differences between the groups at the same time point for new bone and connective tissue variables. Mann-Whitney was used to assess statistical differences between different time points and in the biomaterial variable. Results: Results showed a greater volume of residual biomaterial in the CHA-M than the CHA group (p = 0.007), and there were no significant differences in terms of newly formed bone and connective tissue between CHA and CHA-M after 42 days. Conclusions: This study concluded that both biomaterials improved alveolar bone repair from 7 to 42 days after surgery, and the association of CHA with melatonin gel reduced the biomaterial's biodegradation at the implanted site but did not improve the alveolar bone repair.

Persistent and Enhanced Elimination of Bacteria‐Induced Periodontitis Using a Local Drug Delivery Nanoreactor

AbstractPeriodontitis, one of the most common dental diseases, is the main cause of tooth loss. Bacterial infection and the host immune response are the dominant factors that determine periodontal disease. Therefore, the key factors in the treatment of periodontitis are to remove pathogenic factors and repair periodontal supporting tissues. In this work, a facile and versatile strategy to prepare pH‐sensitive biomineralized nanoparticles constructed with antibiotic to simultaneously deliver antibacterial, anti‐inflammatory, and bone repair capabilities is presented. The experiments in vitro show that the nanoreactor achieves good inhibitory effects on three common periodontal pathogens and has activity against damaging inflammatory mediators, reducing lipopolysaccharide‐induced inflammatory responses. In vivo CT images of the maxillary molar area and histomorphological and immunohistochemical analyses demonstrate that the nanoparticles repair function for periodontal supporting tissues, reverse the loosened alveolar bone tissue, and remodel the periodontal inflammatory microenvironment. Therefore, the present research provides a feasible approach to both prevent the loss of alveolar bone and repair periodontal tissue.

A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Umbilical Cord Stem Cells in Alveolar Cleft Repair

A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Umbilical Cord Stem Cells in Alveolar Cleft Repair

Alveolar Repair Using Cancellous Bone and Beta Tricalcium Phosphate Seeded With Adipose-Derived Stem Cell.

Adipose-derived stem cells (ADSCs) have been subject of several studies due to their abundance, ease of preparation, and application in bone regeneration. We aim to compare effectiveness of alveolar reconstruction utilizing human cancellous freeze-dried graft (HCG) and beta tricalcium phosphate (BTP), both seeded with human ADSC (hADSC) and autologous bone graft (ABG). A 5 × 5 mm alveolar defect in 36 male Wistar rats were treated using: ABG (C), HCG-hADSC (H1), and BTP-hADSC (H2). At 1 and 8 weeks after surgery, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osterix (OSX), and bone morphogenetic protein 2 (BMP2; g/mL) were quantified using immunohistochemistry, while bone tissue volume (BV, mm3), bone tissue volume fraction (BF, percentage), and trabecular thickness of bone (TT, mm) were assessed using micro-computed tomography (CT). One week after surgery, H2 was higher in RUNX2, OSX, ALP, and BMP2 than C (P < .05). Only RUNX2 and OSX were found to be higher in H1 than C, while ALP and BMP2 were higher in H2 than H1. Micro-CT revealed that H2 had a higher TT than C and C had a higher TT than H1 (P < .05). Eight weeks after surgery, both H2 and H1 was higher in RUNX2, OSX, ALP, and BMP2 than C (P < .05). RUNX2 and BMP2 were found to be higher in H1 than H2. Micro-CT revealed that H2 had higher BV and TT than C and H1 (P < .05). Exogenous hADSC strengthened the effectiveness of HCG and BTP to accelerate osteogenesis, osteoconduction, and osteoinduction. The latter was the most successful in bone formation, followed by HCG and ABG.

FTY720 administration results in a M2 associated immunoregulatory effect that positively influences the outcome of alveolar bone repair outcome in mice.

The alveolar bone repair process may be influenced by multiple local and systemic factors, which include immune system cells and mediators. Macrophages allegedly play important roles in the repair process, and the transition of an initial inflammatory M1 profile into a pro-reparative M2 profile theoretically contributes to a favorable repair outcome. In this context, considering immunoregulatory molecules as potential targets for improving bone repair, this study evaluated the role of the immunoregulatory molecule FTY720, previously described to favor the development of the M2 phenotype, in the process of alveolar bone healing in C57Bl/6 (WT) mice. Experimental groups submitted to tooth extraction and maintained under control conditions or treated with FTY720 were evaluated by microtomographic (μCT), histomorphometric, immunohistochemical and molecular analysis to characterize healing and host response features at 0, 1, 3, 7 and 14days. Our results demonstrated that the FTY720 group presented higher bone tissue density, higher bone tissue volume, greater tissue volume fraction, greater number and thickness of trabeculae and a higher number of osteoblasts and osteoclasts than the control group. Accordingly, the bone markers BMP2, BMP7, ALPL, SOST and RANK mRNA expressions increased in the FTY720 treated group. Furthermore, the levels of FIZZ, ARG2 and IL-10 mRNA increased in the FTY720 group together with the presence of CD206+ cells, suggesting that the boost of bone formation mediated by FTY720 involves an increased polarization and activity of M2 macrophages in healing sites. Thus, our results demonstrate that FTY720 favored the process of alveolar bone repair, probably trough a strengthened M2 response, associated with an increased expression of markers osteogenic differentiation and activity markers. Immunoregulatory strategies based in the modulation of macrophage polarization profile can comprise effective tools to improve the bone repair process.

Repair of Alveolar Bone Defects with Osteogenic Polypeptide Modified HA_CF_PEEK Dental Implants

The implant implanted into the body directly interacts with the bone tissue around the implant through its surface. The surface properties of the implant can affect the adhesion, proliferation, and differentiation of surrounding cells and ultimately determine the quality of osseointegration and the effect of implantation surgery. In this project, nano-hydroxyapatite (n-HA) and carbon fiber (CF) were added into the matrix, poly(ether-ether-ketone) (PEEK), forming the composite material HA/CF/PEEK. Since biologically active proteins and peptides can promote cell viability and proliferation, the osteogenic polypeptide sequence BEE1 was polymerized and grafted onto the surface of HA/CF/PEEK composites to generate HA/CF/PEEK-DPP and HA/CF/PEEK-DPP-BEE1 composites. The above materials were tested for physical characterization and in vitro cell activity by establishing a Beagle dog dentition defect model. HA/CF/PEEK type composites were selected for peri-implant bone defect repair and compared with titanium mesh alone or Bio-Gide membrane for alveolar bone defect repair. In the experiment, the HA/CF/PEEK material modified with osteogenic polypeptides changed in element composition, hydrophilicity, and surface morphology. in vitro cell assays detected that the surface of HA/CF/PEEK material modified with osteogenic polypeptides was more conducive to cell adhesion and proliferation and had no cytotoxicity. The peri-implant defect repair test showed that the HA/CF/PEEK-DPP-BEE1 composite material for alveolar bone repair in experimental dogs was better than that of titanium mesh or Bio-Gide membrane. Meanwhile, the mineralization speed and histomorphometry test at the bone defect further proved that this material could better promote bone neogenesis at the defect. Mineralization.

Clinical Application of Allograft Bone of Alveolar Cleft Repair.

To investigate the osteogenic effect of allograft bone (BIO-GENE) and autologous iliac crest bone graft in the alveolar cleft repair. A total of 131 patients with congenital unilateral alveolar cleft who consulted in our hospital from January 2016 to May 2021 were selected and divided into 3 groups according to the different bone restoration materials used. Group A totaling 43 cases was the autologous bone group; group B totaling 41 cases was the BIO-GENE group; and group C totaling 47 cases was the BMP-2+BIO-GENE group. The preoperative and postoperative cone beam CT data of the same patient were imported into MIMICS 21.0 in DICOM format. The preoperative cleft volume and newly formed bone volume were calculated by 3-dimensional reconstruction to measure their osteogenic rate. The differences in osteogenesis rates were not statistically significant in the group B compared with the group A, and in the group C compared with the group B ( P >0.05 for both). The differences in osteogenesis rates were statistically significant in the group C compared with the group A ( P =0.003). Comparative studies found the allograft bone with an ideal artificial material to repair alveolar clefts has become possible. Meanwhile, the addition of BMP-2 in the allograft bone significantly increased the osteogenic rate.

A 3-Dimensional Evaluation of Bone Density in Alveolar Cleft Grafting Methods: Bone Substitutes Versus Autologous Bone.

Secondary alveolar cleft repair using autologous bone graft is currently the gold standard in treating residual alveolar clefts. Despite its effectiveness, this technique is still burdened by several withdrawals, mostly related to donor site morbidity. To decrease disadvantages for patients, numerous attempts in the literature regarding bone substitutes have been described. The aim of this study is to compare the viability of bovine-based replacement bone material with respect of autologous bone graft in alveolar cleft reconstruction, through 3-dimensional alveolar cleft segmentation and bone density evaluation from preoperative and postoperative cone-beam computed tomography. A retrospective cohort study of 10 patients who underwent surgical procedure for alveolar cleft grafting at Sant'Orsola Malpighi University Hospital of Bologna from December 2012 to December 2016 was undertaken. Five patients received autologous bone graft and 5 a bovine bone substitute graft. Preoperative and immediate postoperative orthopanoramic x-rays were recorded. Cone-beam computed tomography scans have recorded both pre and postoperatively. Volumetric evaluation on 3-dimensional cone-beam computed tomography images was performed. Alveolar clefts repaired using substitute bovine bone/biological membrane scaffold had a mean fill of 69.00% of total cleft volume, while this figure was of 67.07% with autologous bone grafting. The immediate postoperative course and subsequent discharge were uneventful for both groups, with a difference in timing. The cost of substitute bovine bone was offset by cost savings associated with a reduction in operative and postoperative and hospitalization time. Bone substitutes showed to be a promising solution in alveolar cleft grafting.

New Insights into the Alveolar Epithelium as a Driver of Acute Respiratory Distress Syndrome.

The alveolar epithelium serves as a barrier between the body and the external environment. To maintain efficient gas exchange, the alveolar epithelium has evolved to withstand and rapidly respond to an assortment of inhaled, injury-inducing stimuli. However, alveolar damage can lead to loss of alveolar fluid barrier function and exuberant, non-resolving inflammation that manifests clinically as acute respiratory distress syndrome (ARDS). This review discusses recent discoveries related to mechanisms of alveolar homeostasis, injury, repair, and regeneration, with a contemporary emphasis on virus-induced lung injury. In addition, we address new insights into how the alveolar epithelium coordinates injury-induced lung inflammation and review maladaptive lung responses to alveolar damage that drive ARDS and pathologic lung remodeling.

Definition of the Region of Interest for the Assessment of Alveolar Bone Repair Using Micro-computed Tomography.

The objective of this study was to evaluate the influence of the extraction socket (distal or lingual root) and the type of region of interest (ROI) definition (manual or predefined) on the assessment of alveolar repair following tooth extraction using micro-computed tomography (micro-CT). The software package used for scanning, reconstruction, reorientation, and analysis of images (NRecon®, DataViewer®, CT-Analyzer®) was acquired through Bruker < https://www.bruker.com > . The sample comprised the micro-CT volumes of seven Wistar rat mandibles, in which the right first molar was extracted. The reconstructed images were analyzed using the extraction sockets, i.e., the distal and intermediate lingual root and the method of ROI definition: manual (MA), central round (CR), and peripheral round (PR). The bone volume fraction (BV/TV) values obtained were analyzed by two-way ANOVA with Tukey's post hoc test (α = 5%). The distal extraction socket resulted in significantly lower BV/TV values than the intermediate lingual socket for MA (P = 0.001), CR (P < 0.001), and PR (P < 0.001). Regarding the ROI, when evaluating the distal extraction socket, the BV/TV was significantly higher (P < 0.001) for MA than for CR and PR, with a lower BV/TV for CR. However, no significant difference was observed for MA (P = 0.855), CR (P = 0.769), or PR (P = 0.453) in the intermediate lingual extraction socket. The bone neoformation outcome (BV/TV) for alveolar bone repair after tooth extraction is significantly influenced by the ROI and the extraction socket. Using the predefined method with a standardized ROI in the central region of the distal extraction socket resulted in the assessment of bone volume, demonstrating the most critical region of the bone neoformation process.

A 3D-printed molybdenum-containing scaffold exerts dual pro-osteogenic and anti-osteoclastogenic effects to facilitate alveolar bone repair

The positive regulation of bone-forming osteoblast activity and the negative feedback regulation of osteoclastic activity are equally important in strategies to achieve successful alveolar bone regeneration. Here, a molybdenum (Mo)-containing bioactive glass ceramic scaffold with solid-strut-packed structures (Mo-scaffold) was printed, and its ability to regulate pro-osteogenic and anti-osteoclastogenic cellular responses was evaluated in vitro and in vivo. We found that extracts derived from Mo-scaffold (Mo-extracts) strongly stimulated osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited differentiation of osteoclast progenitors. The identified comodulatory effect was further demonstrated to arise from Mo ions in the Mo-extract, wherein Mo ions suppressed osteoclastic differentiation by scavenging reactive oxygen species (ROS) and inhibiting mitochondrial biogenesis in osteoclasts. Consistent with the in vitro findings, the Mo-scaffold was found to significantly promote osteoblast-mediated bone formation and inhibit osteoclast-mediated bone resorption throughout the bone healing process, leading to enhanced bone regeneration. In combination with our previous finding that Mo ions participate in material-mediated immunomodulation, this study offers the new insight that Mo ions facilitate bone repair by comodulating the balance between bone formation and resorption. Our findings suggest that Mo ions are multifunctional cellular modulators that can potentially be used in biomaterial design and bone tissue engineering.

A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Fetal Umbilical Cord Stem Cells in Alveolar Cleft Repair

Cleft lip and/or palate (CLP) is one of the most common congenital anomalies1,2 and frequently affects alveolar bone. At many institutions, the standard graft material of alveolar cleft repair (ACR) is autogenous iliac crest bone; however, bone-morphogenetic-protein 2 (BMP-2) delivered on various scaffold materials has shown to be a viable alternative with similar success rates. An alternative potential graft adjunct, fetal human umbilical cord stem cells (h-UCSC), has yet to be explored in vivo.

Failure Rates Based on Alveolar Cleft Size: An Analysis of the Critical Size Defect for rhBMP-2/DBM and ICGB in Alveolar Cleft Repair

Alveolar cleft repair (ACR) using iliac crest bone graft (ICBG) is the standard of care at many institutions for children with complete cleft lip and palate at mixed dentition. Harvesting bone may result in donor site morbidity, protracted operations, and longer hospitalizations. With the advent of recombinant human bone morphogenetic protein (rhBMP-2) and demineralized bone matrix (DBM), the inherent drawbacks of using ICBG during ACR can be avoided. Recent studies demonstrate that rhBMP-2 with DBM (rhBMP-2/DBM) has equal graft success versus ICBG without incurring serious adverse events.

FGF10 Therapeutic Administration Promotes Mobilization of Injury-Activated Alveolar Progenitors in a Mouse Fibrosis Model.

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with dire consequences and in urgent need of improved therapies. Compelling evidence indicates that damage or dysfunction of AT2s is of central importance in the development of IPF. We recently identified a novel AT2 subpopulation characterized by low SFTPC expression but that is enriched for PD-L1 in mice. These cells represent quiescent, immature AT2 cells during normal homeostasis and expand upon pneumonectomy (PNX) and were consequently named injury-activated alveolar progenitors (IAAPs). FGF10 is shown to play critical roles in lung development, homeostasis, and injury repair demonstrated in genetically engineered mice. In an effort to bridge the gap between the promising properties of endogenous Fgf10 manipulation and therapeutic reality, we here investigated whether the administration of exogenous recombinant FGF10 protein (rFGF10) can provide preventive and/or therapeutic benefit in a mouse model of bleomycin-induced pulmonary fibrosis with a focus on its impact on IAAP dynamics. C57BL/6 mice and SftpcCreERT2/+; tdTomatoflox/+ mice aged 8–10 weeks old were used in this study. To induce the bleomycin (BLM) model, mice were intratracheally (i.t.) instilled with BLM (2 μg/g body weight). BLM injury was induced after a 7-day washout period following tamoxifen induction. A single i.t. injection of rFGF10 (0.05 μg/g body weight) was given on days 0, 7, 14, and 21 after BLM injury. Then, the effects of rFGF10 on BLM-induced fibrosis in lung tissues were assessed by H&E, IHC, Masson’s trichrome staining, hydroxyproline and Western blot assays. Immunofluorescence staining and flow cytometry was used to assess the dynamic behavior of AT2 lineage-labeled SftpcPos (IAAPs and mature AT2) during the course of pulmonary fibrosis. We observed that, depending on the timing of administration, rFGF10 exhibited robust preventive or therapeutic efficacy toward BLM-induced fibrosis based on the evaluation of various pathological parameters. Flow cytometric analysis revealed a dynamic expansion of IAAPs for up to 4 weeks following BLM injury while the number of mature AT2s was drastically reduced. Significantly, rFGF10 administration increased both the peak ratio and the duration of IAAPs expansion relative to EpCAMPos cells. Altogether, our results suggest that the administration of rFGF10 exhibits therapeutic potential for IPF most likely by promoting IAAP proliferation and alveolar repair.

Construction of poly-(γ-benzyl‐l‐glutamate) composite microcarriers with osteogenic and angiogenic properties for the restoration of alveolar bone defects

The repair of alveolar bone defects is one of the urgent clinical problems to be solved. Injectable microcarriers show great potential for bone repair due to their ability to fill irregular bone defects. In this study, the ICA@nCP/nHA-g-PBLG composite microcarriers with osteogenic and angiogenic properties were fabricated via double emulsion (W/O/W) method. Firstly, poly-(γ-benzyl‐l‐glutamate) (PBLG) was linkaged onto the surface of nano copper hydroxyphosphate (nCP) and nano hydroxyapatite (nHA) to construct nCP-g-PBLG and nHA-g-PBLG nanohybrids by chemical grafting, respectively. Then, nCP/nHA-g-PBLG porous microcarriers were fabricated via double emulsion (W/O/W) method and immersed in icariin (ICA) solution to obtain ICA@nCP/nHA-g-PBLG composite microcarriers. The composite microcarriers were more conducive to the proliferation of bone marrow mesenchymal stem cells (BMSCs) when the content of nCP and ICA in the composite microcarriers were 0.5 wt% and 0.1 wt%, respectively. The release of Cu2+ in nCP could promote angiogenesis, while the release of ICA could promote the osteogenic differentiation of BMSCs. The ability of ICA@nCP/nHA-g-PBLG microcarriers to restore alveolar bone defects was proved in a rabbit model. In conclusion, the ICA@nCP/nHA-g-PBLG microcarriers exhibited two functions: osteogenesis and angiogenesis, which could be served as a promising implant for alveolar bone defects repair.

Radiological and Microbiological Evaluation of the Efficacy of Alveolar Bone Repair Using Autogenous Dentin Matrix—Preliminary Study

Dental procedures for alveolar bone augmentation may be carried out using autologous bone graft material derived from the patient’s own tooth. The material obtained is subjected to strict procedures aimed at reducing the amount of bacteria in the autograft. The aim of this study was the evaluation of the efficacy of the autogenous dentine matrix produced by grinding the patient’s own tooth for the augmentation of maxillary bone defects and the evaluation of the microbiological status of the material obtained. Alveolar bone repair was performed with an autogenous dentin matrix in four patients. In each case, an autogenous bone graft substitute obtained by grinding the patient’s own tooth was used. The tooth-derived material was then used for alveolar augmentation. The obtained material was tested to assess its microbiological profile. For the purpose of comparison, other materials and tissues were also subjected to microbiological testing. Bone healing was assessed by CBCT (cone beam computed tomography) scanning before and 6 months after surgery using the Hounsfield scale and the ImageJ software. Analysis of the bone regeneration process based on the bone density score in Hounsfield units showed significant differences in measurements on CBCT scans carried out on the treatment site, before surgery, and 6 months after it, using ImageJ software. All bacteria detected in the bone augmentation material constituted the patient’s bacterial flora. The microorganisms present in the augmentation material were also present in the patient’s bone and soft tissues. The use of an autogenous dentin matrix for alveolar bone repair ensures that the proper volume is obtained and that alveolar bone shape is preserved and does not introduce pathogenic microorganisms into the patient. The procedure for preparing and using an autogenous dentin matrix is described based on one clinical case.

133. A Calvarial Defect Murine Model for the Investigation of the Osteogenic Potential of Umbilical Cord Stem Cells in Alveolar Cleft Repair

Purpose: Cleft lip and/or palate (CLP) is one of the most common congenital anomalies and is frequently associated with an alveolar cleft. At many institutions, the standard graft material of alveolar cleft repair (ACR) is autogenous iliac crest bone; however, bone-morphogenetic-protein 2 has shown to be a viable alternative with similar success rates. An alternative potential graft adjunct, umbilical cord stem cells (UCSC), has yet to be explored in vivo. There is ample pre-clinical literature supporting the utility and advantages of UCSC in ACR. Their capacity for self-renewal, pluripotent differentiation, and proliferation allows UCSC to be harnessed for regenerative medicine. Our study seeks to evaluate the feasibility of using UCSC and their osteogenic and regenerative capabilities in a mouse model to improve ACR. Methods: Eighteen FoxN1 mice were included in the study, which were separated into three groups: (1) calvarial defect surgery and no treatment (n=6), (2) calvarial defect surgery with poly(D,L-lactide-co-glycolide) (PLGA) treatment (n=6), (3) calvarial defect surgery with UCSC mixed with PLGA. Calvarial defect surgeries consisted of a sagittal skin incision followed by creation of bilateral, 2mm diameter, full-thickness, parietal bone defects using a 1.8mm dental drill; of note, 2mm is the established critical size defect of murine calvarial bone. The mice underwent microCT imaging at 1-, 2-, 3-, and 4-weeks postoperatively. At 2-weeks postoperatively, one mouse from each group was sacrificed for histologic analysis. At 4-weeks postoperatively, the remaining mice were then sacrificed for histologic examination. Results: All 18 mice underwent calvarial defect surgeries without postoperative complications or infections. All mice were fully ambulatory with no signs of neurologic deficits throughout the 4-week follow-up period. As evidenced by microCT imaging, at 1-, 2-, 3, and, 4-weeks postoperatively, all calvarial defects in groups (1) and (2) remained patent without significant differences in defect sizes between the two groups. Histologically, group (1) and (2) defects demonstrated patency without significant size differences at both 2- or- 4 weeks postoperatively. In contrast, the UCSC group (3) had significantly greater bone fill in the defects at each of the postoperative time points on microCT imaging and demonstrated a lack of patency histologically at final follow-up. Conclusion: These results demonstrate a successful calvarial defect murine model for the investigation of UCSC-mediated osteogenesis and bone repair. Further, our findings provide evidence that PLGA alone has no short-term effect on bone formation nor any unwanted side effects, making it an attractive vehicle for graft substitutes. Further investigation using this UCSC and PLGA scaffold combination in a larger animal porcine model is warranted in hopes of future translation to ACR in patients with CLP.

Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS: New Research Progress and Prospect.

Sepsis is a common critical clinical disease with high mortality that can cause approximately 10 million deaths worldwide each year. Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common clinical complication of sepsis, which occurs primarily as diffuse alveolar injury, hypoxemia, and respiratory distress. The mortality rate of ALI/ARDS is as high as 30%-40%, which greatly endangers human health. Due to the unclear pathogenesis of ALI/ARDS, its treatment is still a worldwide problem. At present, clinical treatment mainly relies on lung-protective ventilation, prone position ventilation, and fluid management. However, there is a lack of effective and specific treatment measures. In recent years, domestic and foreign scholars have committed to basic research on ALI/ARDS, trying to further clarify its pathogenesis and find new targets and methods for the treatment of ALI/ARDS. In this review, we summarize the signaling pathways related to alveolar injury and repair in sepsis-induced ALI/ARDS and their latest research progress. They include the NF-κB, JAK2/STAT3, mitogen-activated protein kinase (MAPK), mTOR, and Notch signaling pathways. Understanding the molecular mechanisms of these signaling pathways in sepsis-induced ALI/ARDS may provide new targets and ideas for the clinical treatment of this disease.

Stem Cells-Loaded 3D-Printed Scaffolds for the Reconstruction of Alveolar Cleft.

The advances in the field of tissue engineering and regenerative medicine have opened new vistas for the repair of alveolar clefts. However, the currently available biomaterials used for the repair of alveolar clefts have poor mechanical properties and biocompatibility, which hinders the treatment outcomes. Here, we aimed to develop 3D printed biomimetic scaffolds that fuses β-tricalcium phosphate (β-TCP) and bone marrow mesenchymal stem cells (BMSCs) for improving the repair of alveolar clefts. The methacrylate gelatin (GelMA) was mixed with β-TCP for the preparation of GelMA/β-TCP hybrid scaffolds via 3D printing platform and chemically cross-linking with UV light. The physicochemical properties of the hydrogel scaffolds were characterized. Moreover, the survival state, proliferation ability, morphological characteristics, and osteogenic induction of BMSCs were examined. The prepared hybrid scaffolds showed good biocompatibility and mechanical properties. BMSCs attached well to the scaffolds and proliferated, survived, differentiated, and stimulated osteogenesis for the reconstruction of alveolar clefts. We expect that use of the prepared hybrid hydrogel scaffold can improve the outcomes of alveolar cleft repair in clinic and expand the application of hybrid hydrogel in tissue engineering repair.