Osteo Science Foundation 2022 Meeting, “Regenerative Solutions to Common Problems”

A Fibrin Hydrogel Encapsulated with Gingival-Derived MSC Extracellular Vesicle-Laden Small Intestine Submucosa Construct Promotes Tongue Myomucosal Regeneration in Rats

Puhan He, DMD; Qilin Xu, DMD, PhD; Qunzhou Zhang, PhD; Rabie M. Shanti, DMD, MD; Anh D. Le, DDS, PhD;

Abstract

Reconstruction of large craniofacial tissue defects, particularly, reconstruction of the tongue defects following ablative surgery of oral cancer, remains one of the major challenges in oral and maxillofacial surgery. Even though much progress has been made in reconstructive principles and techniques, fully functional recovery of the tongue defects is still a great challenge. Currently, microvascular soft tissue free flaps, made up of skin, subcutaneous adipose tissue and fascia, are the gold standard for tongue reconstruction. However, these free flaps do not allow for both structural and functional restoration of the tongue, for example the restoration of its muscular-like tissues and critical vocal, chewing, swallowing, and tasting functions. Meanwhile, harvesting these flaps may result in donor site morbidity and varying degree of edema, limb weakness, and scar formation. In recent years, much efforts have been made to explore the use of mesenchymal stem cells (MSCs) and their derivative cell-free products, e.g. extracellular vesicles (EVs), in combination with biomaterials to generate tissue engineering and regenerative (TE/RM) products to facilitate repair/regeneration of damaged tissues. Most recently, we have shown that combined use of EVs released by gingiva-derived mesenchymal stem cells (GMSC-EVs) and porcine small intestine submucosa extracellular matrix (SIS-ECM) could facilitate myomucosal regeneration in tongue defects of rats. This work aims to bring the TE/RM product closer to clinical application by using GMSC-EVs encapsulated in fibrin hydrogel as a delivery system. We hypothesize that fibrin hydrogel can provide a sustained release of EVs allowing for greater myomucosal regeneration. Specifically, we aim to determine the therapeutic effect and regenerative potential of SIS constructs laden with GMSC-derived EVs encapsulated in fibrin hydrogel in a critical-sized tongue defect model in rats as well as determine potential mechanisms involved.

Presented by

Puhan He

Institution

University of Pennsylvania School of Dental Medicine

Other Affiliations

Hospital of University of Pennsylvania;

Keywords

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Mandibular Alveolar Distraction Osteogenesis to Achieve Adequate Vertical Bone for Implant Placement

Eric Silver, DMD, MD

Abstract

Achieving adequate bony height for pre-prosthetic dental implant placement can be fraught with challenges. Adequate bone for dental implant placement is critical for several reasons, including osseointegration, prevention of peri-implantitis, and proper prosthetic restoration. Several techniques are available, including guided bone regeneration and autogenous grafting. However, these methods are often unpredictable and may involve substantial secondary site morbidity. A method that has been employed to provide improved bony height is alveolar distraction osteogenesis (ADO). With this technique, the segment to be mobilized is created via osteotomies. An internal distractor device is then fixated with an external pin that can be activated by the patient on an outpatient basis. After a latency period of 7 to 10 days, distraction is commenced at a rate of 0.5 to 1 mm per day. Here, we present a case report of a patient who underwent mandibular ADO for eventual dental implant placement due to severely deficient alveolar height.

Presented by

Eric Silver

Institution

Kings County Hospital Center

Keywords

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The Recurrence Risk of Oropharyngeal Malignancies with Hyperbaric Oxygen Therapy of Osteoradionecrosis: a Systematic Review

Pooyan Sadr Eshkevari

Abstract

Objectives: Does HBO increase the risk of recurrence of malignancy? We explored the evidence on potential effect of HBO in recurrence of oropharyngeal cancer in oral osteoradionecrosis through a systematic scoping review.

Materials and Methods: PRISMA extension for Scoping Reviews was followed. Google scholar, clinicaltrials.gov, and Cochrane databases were searched. PICOS: (P) oropharyngeal cancer post radiation, (I) HBO therapy, (C) no HBO therapy control or no control (historical control or expected recurrence rate for the involved tumor), (O) tumor recurrence (metastasis an/or local recurrence), (S) controlled trials, cohorts, series. Duplicates were removed in EndNote, and abstract exclusion was done in Rayyan. 12 records met the inclusion criteria.

Results: Trials: a total of 168 patients were assessed, 78 of which received HBO and 90 served as control. One study recruited patients requiring dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy (53 non-HBO/47 HBO). Recurrence was seen in 6 controls (11%) and 7 HBO patients (15%) without statistical significance. The other trial recruited patients with established ORN and enrolled a total of 68 patients (37 in non-HBO/31 in HBO). A total of 2 recurrences were observed. Cohorts: from 1979 to 2017, these cohorts included 327 non-HBO and 317 HBO patients and the recurrence rate ranged from 0-2. Series: 4 refuting recurrence and 1 supporting it (reporting undiagnosed cancer was misdiagnosed as ORN).

Conclusion: The inconsistency of included RCTs in terms of indication of HBO may not allow pooling of the data for a systematic review. This is however worth exploration for the cohorts and case-series if needed with caution to adjust for the use or not of surgery and/or medication therapy, follow-up length and other associated factors. Majority of the literature consistently refutes potential increase in recurrent rate because of HBO. This needs to be further studied.

Presented by

Pooyan Sadr Eshkevari

Institution

University of Louisville, Oral and Maxillofacial Surgery

Keywords

Osteoradionecrosis, Hyperbaric Oxygen Therapy, Oropharyngeal Cancer, Recurrence

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SCAFFOLD-FREE FACIAL NERVE CONDUIT ENGINEERED USING DENTAL PULP STEM CELLS

Matthew Dailey DDS, MD; Michelle Drewry, MS; Kristi Rothermund BS, HTL (ASCP); Fatima Syed-Picard MSE, PhD

Abstract

Current treatments of facial nerve injury result in poor functional outcomes due to inefficient axon regeneration and aberrant reinnervation of target muscles. To address these clinical challenges, bioactive scaffold-free cell sheets were engineered using dental pulp stem/progenitor cells and their aligned extracellular matrix (ECM). Dental pulp stem/progenitor cells (DPCs) endogenously supply high levels of neurotrophic factors (NTFs), growth factors capable of stimulating axonal regeneration, and an aligned extracellular matrix (ECM) provides guidance cues to direct axon extension. Human DPCs were grown on a substrate comprising parallel micro-grooves, inducing the cells to align and deposit a linearly aligned, collagenous ECM. The resulting cell sheets were robust and could be easily removed from the underlying substrate. DPC sheets produced NTFs at levels previously shown capable of promoting axon regeneration, and moreover, inducing DPC alignment increased the expression of select NTFs relative to unaligned controls. Furthermore, the aligned DPC sheets were able to stimulate functional neuritogenic effects in neuron-like cells in vitro. Neuronally- differentiated neuroblastoma cells produced neurites that were significantly more oriented and less branched when cultured on aligned cell sheets relative to unaligned sheets. Our data demonstrates that the linearly aligned DPC sheets can both support axon regeneration and improve axonal guidance which, when applied to a facial nerve injury, will result in more accurate reinnervation. Impact: We have developed a bioactive scaffold-free cell sheet that enhances axon regeneration and effectively orients axon extension. This scaffold-free cell sheet may bypass the challenges associated with the current standard of care for treating nerve injuries. The aligned DPC sheets generated here could be used in combination with commercially available nerve conduits to enhance their bioactivity or be formed into stand-alone scaffold free nerve conduits capable of facilitating improved facial nerve recovery.

Presented by

Matthew Dailey <daileymt@upmc.edu>

Institution

University of Pittsburgh

Other Affiliations

Department of Oral and Maxillofacial Surgery, Department of Oral Biology, Center for Craniofacial Regeneration, Department of Bioengineering, McGowan Institute for Regenerative Medicine

Keywords

Nerve, Regeneration, Nerve Regeneration, Stem Cells, Translational Science

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Innervated Bioengineered Salivary Gland to Model SARS-CoV-2 Infectivity

Caitlynn M. L. Barrows, Danielle Wu, Robert Witt, Laura Smith Callahan, Simon Young, Mary C. Farach-Carson

Abstract

The ongoing COVID-19 pandemic reports >33 million confirmed cases and over 1 million deaths globally. The virus, severe acute respiratory syndrome Coronavirus – 2 (SARS-CoV-2), primarily infects lung tissue by binding to the angiotensin converting enzyme 2 (ACE2) receptor. The primary means of transmission is airborne through inhaled respiratory droplets leading to infections in the lungs or respiratory pathway. SARS-CoV-2 also has the potential to infect oral tissues, specifically salivary glands, evidenced by the presence of SARS-CoV-2 particles in whole saliva. Tissue engineering strategies for salivary gland regeneration has provided a unique model for testing the ability for SARS-CoV-2 to infect salivary glands. However, tissue engineered models require a ductal system that mimics native tissue as the ductal cells interface directly with the oral cavity which is the likely route of salivary gland infection by SARS-CoV-2. To achieve a ductal lumen-like structure requires additional cues, additionally, tissue engineering strategies rely on the differentiation of salivary stem/progenitor cells which do not initially express ACE2. Here we examine the potential to utilize cues provided by the nervous system to induct ductal lumen formation and the effects of different basement membrane components on ACE2 expression.

Presented by

Caitlynn Barrows

Institution

University of Texas Health Science Center - School of Dentistry, Houston, TX

Other Affiliations

. Christiana Care Health Center, Newark, Delaware, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA

Keywords

Salivary Gland Biology, Tissue Engineering, SARS-CoV-2, ACE2

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Does Bone Grafting Increase Primary Stability of Dental Implants Placed in Sites of Previous Failure?

Brian R Carr DMD, Timothy W Neal DDS, Richard Finn DDS

Abstract

Purpose The purpose of this study was to determine if bone grafting at the time of implant removal due to failure increases primary stability of an implant subsequently placed at the same site.

Materials and Methods A retrospective cohort study was conducted to evaluate dental implants placed between 2015 and 2016 at the Veterans Affairs North Texas Health Care System in Dallas. The primary predictor variable was placement of a bone graft (1cc of MinerOss; manufactured by Collagen Matrix, Inc., Oakland, NJ) at the time of explantation due to implant movement/failure. The primary outcome variable was primary stability at the time of reimplantation, defined as resistance of the implant to rotational forces, measured as insertional torque to the lowest Ncm which stopped the implant motor from further advancing the implant and the next 10 Ncm value not achieved ( ie , >30 Ncm, <40 Ncm). All implants were placed after six months from the time of explantation. A secondary outcome variable was early implant failure, defined as implant exfoliation noted by the patient or failure due to implant movement or pain necessitating explantation prior to prosthesis loading. Descriptive, bivariate, and multiple logistic regression analyses were performed with p<0.05 used to determine statistical significance.

Results One hundred and three patients had 214 implants placed. Of the 214 implants placed, eight were placed in sites of previous failure. Five of the eight implants were placed in sites that were bone grafted at the time of explantation, while three of the implants were placed in sites that were not bone grafted. The mean insertional torque value at reimplantation for bone grafted sites was higher than sites that were not bone grafted (40-49 Ncm versus 30-39 Ncm), but this was not statistically significant (Student’s t-test, p=0.174).

Subgroup analysis found that the bone grafting group had one early failure (20%), and the non-bone grafting group had one early failure (33%). There was no significant difference between bone grafting at the time of explantation and the incidence of early failures after reimplantation (OR 0.500; 95% CL 0.02-12.90, p=1).

Discussion The results of this preliminary study suggest there is no association between bone grafting at the time of explantation and primary stability as determined by insertional torque values of dental Implants placed in sites of previous failure. Subgroup analysis showed bone grafting at the time of explantation was not associated with protection against subsequent early failure.

Presented by

Brian Carr

Institution

University of Texas Southwestern Medical Center, Department of Surgery, Division of Oral and Maxillofacial Surgery

Other Affiliations

Veterans Affairs North Texas Health Care System in Dallas

Keywords

Dental Implants; Bone Grafting

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Available February 18th, 1-2pm

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Osteo Science Foundation 2022 Meeting, “Regenerative Solutions to Common Problems”