Transferring emergence profile and position of interim restorative implant fixture. A novel digital technique.

The present technical article describes a protocol to digitally reproduce the emergence profile of an interim implant prosthesis (IP) and to transfer its macrogeometry into the definitive restoration. The purpose of this protocol was to minimize alterations in the gingival architecture developed during the interim restorative phase of a single implant that could potentially jeopardize its esthetic outcome. The process included obtaining an intraoral scan with the interim IP in situ, a duplicate of this intraoral scan that was used to capture the exact position of the implant, and an extraoral scan of the prosthesis. These data could then be imported into IOS software to create a model where the patients' soft tissue was incorporated with precision, allowing for the fabrication of a definitive crown with an optimal soft tissue adaptation. As there are few articles in the scientific literature that have reported a consistent method to replicate the emergence profile of an interim IP, the present technical article aims to highlight the potential of utilizing the emergence profile of an interim IP created by IOS software.

Guided Bone Regeneration: Novel Use of Fixation Screws as an Alternative to Using the Buccoapical Periosteum for Membrane Stabilization With Sutures-Two Case Reports.

Guided bone regeneration (GBR) requires a stable graft-membrane complex. This article presents a novel technique that uses membrane fixation screws to serve as anchors for membrane stabilization sutures without the need for periosteal dissection and biting of the buccoapical periosteum. This technique may be a viable alternative when there is a preference to avoid the complexities of periosteal suturing and direct membrane fixation using tacks or screws. The technique, which utilizes anchoring screws as mooring lines, can be used at the time of tooth extraction as well as for ridge augmentation of an edentulous site in preparation for future dental implant placement. Two case reports are presented that illustrate the feasibility of the technique, in which the integrity and stability of a resorbable membrane is preserved prior to final closure, suggesting that screws used as anchors for stabilization sutures might be a predictable option when addressing challenging horizontal defects requiring GBR.

The Ribroast Technique™: An Alternative Method to Stabilize a Resorbable Collagen Membrane for Guided Bone Regeneration.

Stabilization of the graft-membrane complex during guided bone regeneration is a critically important aspect of implant dentistry. Several articles in the dental literature have introduced the utilization of periosteal biting stabilization sutures, rather than fixation screws and pins, to stabilize a bioabsorbable collagen membrane. This article reviews the concept of stabilization using sutures in periodontal regeneration and describes an alternative method, the Ribroast technique™, to stabilize a bioabsorbable membrane, whereby single periosteal biting horizontal mattress sutures are placed along the length of the defect to achieve sufficient stabilization. Two cases are presented that highlight the utility of this technique. Guidelines and limitations for the use of periosteal biting sutures are also discussed along with considerations and protocols that may be useful for improving treatment outcomes.

Use of a Sugar-Crosslinked Collagen Membrane in Conjunction With a Dehydrated Amnion/Chorion Membrane for Guided Bone Regeneration Around Immediate Implants.

Several bioabsorbable membranes have been proposed to exclude soft-tissue ingrowth and to stabilize the bone graft when guided bone regeneration (GBR) is performed. The properties of the various membranes differ slightly due to variances in composition and manufacturing processes affecting their handling and suitability for specific techniques. The aim of this article is to present a technique to perform GBR with the use of a sugar-crosslinked absorbable collagen membrane in conjunction with a dehydrated amnion/chorion membrane (dHACM). This technique can be used to perform GBR at the time of tooth extraction and for ridge augmentation of an edentulous site in preparation for future dental implant placement. The use of a collagen membrane in combination with a dHACM can facilitate stabilization of the bone graft and membrane by providing the benefits of a long-lasting bioabsorbable collagen membrane in addition to the unique benefits of an amnion/chorion membrane, which has been shown to provide growth factors to the surgical site that have potential to enhance regenerative outcomes.

Thermally responsive hydrogel for atrial fibrillation related stroke prevention.

Atrial fibrillation induced stroke accounts for up to 15% of all strokes. These strokes are caused approximately 90% of the time by clot formation in the left atrial appendage (LAA). To prevent these clots, the most common approach is to administer blood thinners. However, contraindications prevent some people from being able to have blood thinners. Devices have been developed to seal the LAA to prevent clot formation in these patients. Current devices, such as the LARIAT® tie off the LAA theoretically preventing blood from entering the LAA. These have had limited clinical success mainly due to failure to completely close the LAA leaving holes and orifices for thrombi to form. To overcome this lack of complete closure, many surgeons use off-label approaches, classically filling the LAA filamentous coils, to cover these holes. Although this usually helps largely cover the holes, placement is challenging, the coils can migrate, the holes are not fully closed as there is space within and around the coils that don't fully mold to the LAA geometry. Furthermore, the coils can develop device related thrombi defeating their purpose. Therefore, these are not fully sufficient to complement the closure techniques in closing the LAA. To address limitation of the closure devices and coil sealing of remaining holes, we developed a thermally responsive hydrogel (Thermogel) that solidifies once injected into the LAA to uniformly and fully close off the LAA thus preventing clot formation and device related thrombi. This Thermogel consists of three portions: 1) a structural component composed of thiolated Pluronic F127 for gel to solid transition following injection, 2) Heparin for anticoagulation, and 3) Dopamine for adhesion to the surrounding endothelium in the turbulent flow encountered in cardiovascular applications. Here we have demonstrated that Thermogel, in conjunction with the LARIAT®, is capable of filling the defects in small and large animals through catheter injection. Thermogel was biocompatible and led to atrophy of the LAA at 5 weeks in a large animal model. Given the advantages of this Thermogel for sealing this defect and ability to be delivered through an endovascular approach, Thermogel presents a viable adjuvant to current occlusion-based treatments for sealing cardiovascular defects.

Transferring the finish line of an interim restorative to the definitive cast in biologically oriented preparation technique (BOPT) procedures: A dental technique.

The biologically oriented preparation technique (BOPT) uses a vertical tooth preparation and simultaneously a controlled rotary instrumentation of the gingival sulcus. The resulting blood clot is stabilized with the interim restoration. However, accurate transfer of the emergence profile of the interim crown to the definitive restoration is essential to maintain the gingival architecture. This technique article describes clinical and laboratory procedures to predictably transfer the emergence profile of the interim crown to duplicate the gingival architecture in the definitive restoration.

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique.

BACKGROUND: Bone marrow aspirate (BMA) is a common source for harvesting mesenchymal stem cells (MSCs), other progenitor cells, and associated cytokines and growth factors to be used in the biologic treatment of various orthopaedic pathologies. The aspirate is commonly centrifuged into a concentrated volume that can be immediately administered to a patient using commercially available kits. However, the handling and efficacy of BMA concentrate (BMAC) are still controversial. PURPOSE: To characterize BMA versus BMAC for MSC quantity, potency, and cytokine profile. STUDY DESIGN: Controlled laboratory study. METHODS: From 8 participants (age, 17-68 years), 30 mL of bone marrow was aspirated by a single surgeon from either the proximal humerus or distal femur and was separated into 2 equal samples. One sample was kept as BMA, and the other half was centrifuged into BMAC. The 2 samples then underwent flow cytometry for detection of MSCs, cell analysis for colony-forming units (CFUs), and cytokine profiling. A 2-tailed t test was used to detect differences between MSCs, CFUs, and cytokine density concentrations between BMA and BMAC. RESULTS: The average concentration of MSCs in both BMA and BMAC was 0.001%. Average MSC events detected by flow cytometry were significantly higher in BMA versus BMAC (15.1 and 8.1, respectively; P < .045). Expanded MSCs demonstrated similar phenotypes, but CFUs were significantly increased in BMA compared with BMAC (104 vs 68 CFUs, respectively; P < .001). Total protein concentration and cytokine profiling demonstrated great variability between BMA and BMAC and between patients. Most importantly, BMAC failed to concentrate MSCs in 6 of 8 samples. CONCLUSION: There is great variability in MSC concentration, total protein concentration, and cytokine profile between BMA and BMAC. CLINICAL RELEVANCE: When studying the clinical efficacy of BMAC, one must also evaluate the sample itself to determine the presence, concentration, and potency of MSCs if this is to be considered a cell-based therapy. Further standard operating procedures need to be investigated to ensure reproducible results and appropriate treatments.

The Use of a Collagen Scaffold to Augment Buccal Ridge Contour Concurrently with Implant Placement: A Two-Case Report.

The aim of this report is to present a technique for buccal soft tissue contour augmentation with the use of a porcine volume-stable collagen matrix (VSCM). Augmentation of buccal soft tissue at the time of implant placement is often a necessity but is mostly performed using autogenous tissue. The technique using a VSCM can be done at the time of implant placement or, in the case of a two-stage procedure, at the time of implant uncovering. Here, clinical outcomes are reported in two cases when using VSCM concurrently with implant placement at sites in need of buccal contour augmentation to achieve a functional, esthetic result. The use of a xenograft poses several advantages over autogenous tissue while providing similar gains in soft tissue thickness. By eliminating the need to harvest a soft tissue graft from the palate, patient morbidity is reduced, and the reliance on palatal tissue thickness, to determine the amount of achievable augmentation, is eliminated.

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting.

Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.

Acute Physiologic Effects of Performing Yoga in The Heat on Energy Expenditure, Range of Motion, and Inflammatory Biomarkers.

Performing yoga in a heated environment (HY) is a popular exercise mode purported to improve range of motion (ROM), body composition, and aerobic fitness. The purpose of this investigation was to compare a session of HY to room temperature yoga (RTY) with regards to ROM, oxygen consumption, caloric expenditure, and biomarkers of acute stress and inflammation. Sixteen experienced yoga practitioners (F14, M2; 40 ± 11yr; 22.6 ± 1.8 kg/m2) completed a 1-hour standardized Bikram sequence in HY (105°F, 40°C) and RTY (74°F, 23.3°C) conditions (order of conditions randomized, humidity standardized at 40%). Intra-exercise metabolic gas exchange and heart rate (HR) was monitored using a metabolic cart. ROM measures were taken pre and post-exercise at the elbow, shoulder, hip, and knee. Cytokines interleukin 6,10 (IL-6, IL-10) and tumor-necrosis-factor alpha (TNF-α) were analyzed from blood samples collected pre- and 30-minutes post-exercise. Intra-exercise metabolic gas exchange and heart rate (HR) was monitored using a metabolic cart. Both bouts elicited similar acute changes in ROM although HY elicited a greater increase in hip abduction (RTYΔ° = 2.3 ± 1.3|HYΔ° = 6.6 ± 1.5; p < 0.05). Mean VO2, peak VO2, %VO2max, HR, and kcal expenditure did not differ between conditions. RER was lower during the HY (RTY = 0.95 ± 0.02| HY = 0.89 ± 0.02; p < 0.05) with a concomitant elevation in fat oxidation (RTY = 0.05 ± 0.01|HY = 0.09 ± 0.01, g·min-1; p < 0.05) and decrease in carbohydrate oxidation (RTY = 0.51 ± 0.04|HY = 0.44 ± 0.03, g·min-1; p < 0.05). Serum IL-6 was increased (15.5 ± 8.0-fold) following HY only (p < 0.05). HY does not significantly elevate aerobic energy cost compared to RTY but may acutely increase fat substrate utilization and hip ROM. Future studies remain needed to establish dose-response relationships for including HY or RTY into well-rounded fitness programs.

Biomimetic Tissue Engineering: Tuning the Immune and Inflammatory Response to Implantable Biomaterials.

Regenerative medicine technologies rely heavily on the use of well-designed biomaterials for therapeutic applications. The success of implantable biomaterials hinges upon the ability of the chosen biomaterial to negotiate with the biological barriers in vivo. The most significant of these barriers is the immune system, which is composed of a highly coordinated organization of cells that induce an inflammatory response to the implanted biomaterial. Biomimetic platforms have emerged as novel strategies that aim to use the principle of biomimicry as a means of immunomodulation. This principle has manifested itself in the form of biomimetic scaffolds that imitate the composition and structure of biological cells and tissues. Recent work in this area has demonstrated the promising potential these technologies hold in overcoming the barrier of the immune system and, thereby, improve their overall therapeutic efficacy. In this review, a broad overview of the use of these strategies across several diseases and future avenues of research utilizing these platforms is provided.

Immune tuning scaffold for the local induction of a pro-regenerative environment.

In mammals, tissue regeneration is accomplished through a well-regulated, complex cascade of events. The disruption of the cellular and molecular processes involved in tissue healing might lead to scar formation. Most tissue engineering approaches have tried to improve the regenerative outcome following an injury, through the combination of biocompatible materials, stem cells and bioactive factors. However, implanted materials can cause further healing impairments due to the persistent inflammatory stimuli that trigger the onset of chronic inflammation. Here, it is described at the molecular, cellular and tissue level, the body response to a functionalized biomimetic collagen scaffold. The grafting of chondroitin sulfate on the surface of the scaffold is able to induce a pro-regenerative environment at the site of a subcutaneous implant. The early in situ recruitment, and sustained local retention of anti-inflammatory macrophages significantly reduced the pro-inflammatory environment and triggered a different healing cascade, ultimately leading to collagen fibril re-organization, blood vessel formation, and scaffold integration with the surrounding native tissue.

Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes.

Clinical trials have demonstrated that heparan sulfate (HS) could be used as a therapeutic agent for the treatment of inflammatory diseases. Its anti-inflammatory effect makes it suitable for the development of biomimetic innovative strategies aiming at modulating stem cells behavior toward a pro-regenerative phenotype in case of injury or inflammation. Here, we propose collagen type I meshes fabricated by solvent casting and further crosslinked with HS (HS-Col) to create a biomimetic environment resembling the extracellular matrix of soft tissue. HS-Col meshes were tested for their capability to provide physical support to stem cells' growth, maintain their phenotypes and immunosuppressive potential following inflammation. HS-Col effect on stem cells was investigated in standard conditions as well as in an inflammatory environment recapitulated in vitro through a mix of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-gamma; 20 ng/ml). A significant increase in the production of molecules associated with immunosuppression was demonstrated in response to the material and when cells were grown in presence of pro-inflammatory stimuli, compared to bare collagen membranes (Col), leading to a greater inhibitory potential when mesenchymal stem cells were exposed to stimulated peripheral blood mononuclear cells. Our data suggest that the presence of HS is able to activate the molecular machinery responsible for the release of anti-inflammatory cytokines, potentially leading to a faster resolution of inflammation.

Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue.

Musculoskeletal reconstruction is an ongoing challenge for surgeons as it is required for one out of five patients undergoing surgery. In the past three decades, through the close collaboration between clinicians and basic scientists, several regenerative strategies have been proposed. These have emerged from interdisciplinary approaches that bridge tissue engineering with material science, physiology, and cell biology. The paradigm behind tissue engineering is to achieve regeneration and functional recovery using stem cells, bioactive molecules, or supporting materials. Although plenty of preclinical solutions for bone and cartilage have been presented, only a few platforms have been able to move from the bench to the bedside. In this review, we highlight the limitations of musculoskeletal regeneration and summarize the most relevant acellular tissue engineering approaches. We focus on the strategies that could be most effectively translate in clinical practice and reflect on contemporary and cutting-edge regenerative strategies in surgery. Stem Cells Translational Medicine 2017;6:2186-2196.

Hyaluronic acid coatings as a simple and efficient approach to improve MSC homing toward the site of inflammation.

A major challenge in regenerative medicine is to improve therapeutic cells' delivery and targeting using an efficient and simple protocol. Mesenchymal stem cells (MSC) are currently employed for the treatment of inflammatory-based diseases, due to their powerful immunosoppressive potential. Here we report a simple and versatile method to transiently overexpress the hyaluronic acid (HA) receptor, CD44, on MSC membranes, to improve their homing potential towards an inflammatory site without affecting their behavior. The effect of HA-coatings on murine MSC was functionally determined both, in vitro and in vivo as a consequence of the transient CD44 overexpression induced by HA. Data obtained from the in vitro migration assay demonstrated a two-fold increase in the migratory potential of HA-treated MSC compared to untreated cells. In an LPS-induced inflamed ear murine model, HA-treated MSC demonstrated a significantly higher inflammatory targeting as observed at 72 hrs as compared to untreated cells. This increased accumulation for HA-treated MSC yielded a substantial reduction in inflammation as demonstrated by the decrease in the expression of pro-inflammatory markers and by the induction of a pro-regenerative environment.

Corrigendum: Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes.

[This corrects the article on p. 54 in vol. 5, PMID: 28983481.].