Autologous Ilium Grafts: Long‐Term Results on Immediate or Staged Functional Rehabilitation of Mandibular Segmental Defects Using Dental Implants after Tumor Resection

BackgroundIt is a challenge for clinicians to restore oral function in patients with segmental defects of the mandible because of tumor extirpation. Dental implant therapy following vascularized autologous ilium grafts is an effective method to restore oral function in patients with mandibular segmental defects.PurposeThe aim of this retrospective study was to investigate the long‐term clinical outcomes of ilium grafts combined with immediate or staged mandibular dental implant therapy to restore craniofacial defects resulting from tumor resection.Materials and MethodsOver a 5‐year period (2000–2004), 32 patients who underwent mandibular segmental resection for tumors were treated with vascularized ilium grafts to augment bone volume. Seventeen patients received phase I therapy (immediate placement of implants), and 15 patients underwent phase II therapy (delayed placement of implants). A total of 110 dental implants were placed in these patients for mandibular restoration of the defective areas. Information regarding implant success and survival rates, marginal bone loss, soft tissue inflammation, complications of prosthesis, and patient satisfaction for the 8 to 12 years following oral reconstruction was obtained from patient records.ResultsAlthough there was mild evidence of bone graft resorption, the vascularized autogenous ilium bone grafts were successful in all patients. The cumulative patient survival and success rate of the implants were 96.4% and 91.8%, respectively. The mean peri‐implant bone resorption ranged from 1.0 to 1.2 mm over the 8‐ to 12‐year follow‐up period. The annual mean number of complications/repairs was from 0.11 to 0.07 per patient during the 8‐ to 12‐year follow‐up. Over 80% of the patients were fully satisfied with their restoration of oral function.ConclusionsThis study demonstrates that reconstruction of mandibular segmental defects because of resection of mandibular tumors using dental implants therapy combined with vascularized autogenous ilium grafts is an effective method to restore oral function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112185/1/cid12169.pd

Restoration of Oral Function for Adult Edentulous Patients with Ectodermal Dysplasia: A Prospective Preliminary Clinical Study

BackgroundTherapy with zygomatic implants (ZIs) or conventional implants (CIs) has proven to be an effective method to restore oral function for systemically healthy patients. However, it is still a major challenge to fully restore oral function to edentulous adult patients with ectodermal dysplasia (ED).PurposeThe aim of this study was to determine an effective treatment protocol for restoring oral function using ZIs and CIs to edentulous adult ED patients.Materials and MethodsTen edentulous adult ED patients were treated in this study. The treatment protocol involved the following: (1) bone augmentation in the region of the anterior teeth; (2) placement of two ZIs and four CIs in the maxilla, and four CIs in the mandible; (3) fabrication of dental prosthesis; and (4) psychological and oral education. Following treatment of these patients, implant success rates, biological complications, patient satisfaction, and psychological changes were recorded.ResultsAlthough there was evidence of bone graft resorption in the maxilla, bone augmentation of the mandible was successful in all patients. Nine CIs in the maxilla failed and were removed. All ZIs were successful, and the CIs success rates were 77.50% in the maxilla and 100% in the mandible, with a mean of 88.75%. The mean peri‐implant bone resorption for the CIs ranged from 1.3 ± 0.4 mm to 1.8 ± 0.6 mm, and four cases exhibited gingival hyperplasia in the maxilla and mandible. One hundred percent of the patients were satisfied with the restoration of their oral function, and >50% of the patients exhibited enhanced self‐confidence and self‐esteem.ConclusionsThis study demonstrates that oral function can be restored in edentulous adult ED patients using a comprehensive and systematic treatment protocol involving psychological and oral education, bone augmentation, implant placement, and denture fabrication. Despite these positive outcomes, bone augmentation remains challenging in the anterior region of the maxilla for edentulous adult ED patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115948/1/cid12296.pd

Gadolinium‐Doped Iron Oxide Nanoprobe as Multifunctional Bioimaging Agent and Drug Delivery System

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116012/1/adfm201502868.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116012/2/adfm201502868-sup-0001-S1.pd

The Bone-Forming Effects of HIF-1α-Transduced BMSCs Promote Osseointegration with Dental Implant in Canine Mandible

The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore the oral function. Gene-transduced stem cells provide a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants with tissue engineering technology. Our previous studies have demonstrated that the hypoxia-inducible factor-1α (HIF-1α) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the function of HIF-1α was validated for the first time in a preclinical large animal canine model in term of its ability to promote new bone formation in defects around implants as well as the osseointegration between tissue-engineered bone and dental implants. A lentiviral vector was constructed with the constitutively active form of HIF-1α (cHIF). The ectopic bone formation was evaluated in nude mice. The therapeutic potential of HIF-1α-overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1α mediated canine BMSCs significantly promoted new bone formation both subcutaneously and in mesi-implant defects, including increased bone volume, bone mineral density, trabecular thickness, and trabecular bone volume fraction. Furthermore, osseointegration was significantly enhanced by HIF-1α-overexpressing canine BMSCs. This study provides an important experimental evidence in a preclinical large animal model concerning to the potential applications of HIF-1α in promoting new bone formation as well as the osseointegration of immediate implantation for oral function restoration

Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone

miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects

Abstract Background Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge. Many studies have emphasized the osteogenic and angiopoietic abilities of stem cells for tissue regeneration. We previously showed that microRNA-21 (miRNA-21) can promote angiogenesis in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). In the present study, the role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated. Methods Western blotting and qPCR were performed to investigate the influences of miRNA-21 on osteogenic differentiation of BMSCs. The effects of miRNA-21 on PTEN/PI3K/Akt/HIF-1α pathway were also assessed using western blotting. To further evaluate the roles of miRNA-21 in osteogenesis in vivo, we conducted animal experiments in rat and canine. New bone formation was assessed using micro-CT and histological methods. Results In the present study, we found that miRNA-21 promotes the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro. Using gain- and loss-of-function studies, we found that miRNA-21 promoted the osteogenic ability of BMSCs by increasing P-Akt and HIF-1α activation. Finally, we verified the essential role of miRNA-21 in osteogenesis by implanting a miRNA-21-modified BMSCs/β-tricalcium phosphate (β-TCP) composite into critical size defects. Radiography, micro-CT, and histology revealed significantly greater volume of new bone formation in the miRNA-21 group than in the control group. Conclusion In conclusion, our study demonstrated an essential role of miRNA-21 in promoting maxillofacial bone regeneration via the PTEN/PI3K/Akt/HIF-1α pathway

MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing.

Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis

Immunohistochemical analysis of new bone formation in each group in the subcutaneous nude mice.

<p>Immunostaining for GFP of (a) CMPC group, (b) Lenti-GFP group, (c) Lenti-HIF group, and (d) Lenti-cHIF group. The GFP, HIF, and cHIF groups show positive brown staining in fibroblastic-like tissue and bone matrix (red arrow). The strong HIF-1α expression was stained in both the bone and the surrounding fibroblastic-like tissue (red arrows) in (g) Lenti-HIF group and (h) Lenti-cHIF group. There was no obvious positive staining in (e) the CMPC group or (f) the Lenti-GFP group (a–h, 400×).</p

Radiography and micro-CT evaluation of bone repair and osseointegration at 12 weeks after implantation.

<p>X-ray images were taken immediately after surgery and at 12 weeks (A-a). The morphology of the newly formed bone in the defects was reconstructed using micro-CT (A-b). Morphometric analysis of the BV/TV (B-a), BMD (B-b), Tb.N (B-c), and Tb.Th (B-d). (**, <i>P</i><0.01, the target gene groups compared to the blank group, the GFP group or the CMPC group).</p

New bone formation and mineralization determined histomorphometrically by TE, CA, and AL fluorescent quantification, which represent the mineralization level at 12 weeks after the operation (A).

<p>Parts a, b, c, d, and e are confocal laser scanning microscopy images for each group. Parts a4, b4, c4, d4, and e4 represent merged images of the three fluorochromes for the same group. Parts a5, b5, c5, d5, and e5 represent the merged images of the three fluorochromes together with the plain confocal laser microscopy image for the same group. (B) The graph shows the percentage of each fluorochrome area in each group. (** <i>P</i><0.01, target gene groups compared with the GFP group, Blank group or CMPC group; #, <i>P</i><0.05, the cHIF group compared to the HIF group).</p