Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking

Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn2+) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO2 group, Zn2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.

Postoperative Inhaled Steroids Following Glottic Airway Surgery Reduces Granulation Tissue Formation

Objectives: Transoral laser surgery for glottic stenosis (transverse cordotomy and anteromedial arytenoidectomy (TCAMA)) is often complicated by granulation tissue (GT) formation. GT can cause dyspnea and may require surgical removal to alleviate airway obstruction. Inhaled corticosteroids (ICS) have been shown to reduce benign vocal fold granulomas, however its use to prevent GT formation has not been described. We aimed to analyze the effect of immediate postoperative ICS on GT formation in patients undergoing transoral laser surgery for glottic stenosis. Methods: A retrospective analysis of patients that had transoral laser surgery for glottic stenosis from 2000 to 2019 was conducted. Surgical instances were grouped into those that received postoperative ICS and those that did not. Demographics, diagnosis, comorbidities, intraoperative adjuvant therapy, and perioperative medications were collected. Differences in GT formation and need for surgical removal were compared between groups. A multivariate exact logistic regression model was performed. Results: Forty-four patients were included; 16 required 2 glottic airway surgeries (60 surgical instances). Of the 23 instances where patients received immediate postoperative ICS, 0 patients developed GT; and of the 37 instances that did not receive postoperative ICS, 15 (40.5%) developed GT ( P < .0001). Eight (53.3%) of these cases returned to the OR for GT removal. ICS use was solely associated with the absence of GT formation ( P = .042) in the multivariate analysis. Conclusions: Immediate postoperative use of ICS seems to be a safe and effective method to prevent granulation tissue formation and subsequent surgery in patients following transoral laser airway surgery for glottic stenosis.

Proliferation activity in the polyps of Cassiopea xamachana: where the planuloid buds grow

Polyps of the Cassiopeidae family possess a unique type of asexual reproduction by producing free-swimming buds — planuloids. The process of planuloid development and transformation to polyp has been described earlier, however, the source of tissue formation is still poorly studied. Using the method of EdU incorporation we have analyzed DNA synthesis activity during planuloid formation and growth in Cassiopea xamachana. We revealed the active proliferation zone at the early stage of bud formation. This zone continued to function during planuloid growth, providing the formation of polyp structures, and preserved in polyp calyx after metamorphosis. Its proliferation activity varied at different growth stages, whereas the localization remained relatively the same.

mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype

Diabetic wounds are recalcitrant to healing. One of the important characteristics of diabetic trauma is impaired macrophage polarization with an excessive inflammatory response. Many studies have described the important regulatory roles of microRNAs (miRNAs) in macrophage differentiation and polarization. However, the differentially expressed miRNAs involved in wound healing and their effects on diabetic wounds remain to be further explored. In this study, we first identified differentially expressed miRNAs in the inflammation, tissue formation and reconstruction phases in wound healing using Illumina sequencing and RT-qPCR techniques. Thereafter, the expression of musculus (mmu)-miR-145a-5p (“miR-145a-5p” for short) in excisional wounds of diabetic mice was identified. Finally, expression of miR-145a-5p was measured to determine its effects on macrophage polarization in murine RAW 264.7 macrophage cells and wound healing in diabetic mice. We identified differentially expressed miRNAs at different stages of wound healing, ten of which were further confirmed by RT-qPCR. Expression of miR-145a-5p in diabetic wounds was downregulated during the tissue formation stage. Furthermore, we observed that miR-145a-5p blocked M1 macrophage polarization while promoting M2 phenotype activation in vitro. Administration of miR-145a-5p mimics during initiation of the repair phase significantly accelerated wound healing in db/db diabetic mice. In conclusion, our findings suggest that rectifying macrophage function using miR-145a-5p overexpression accelerates diabetic chronic wound healing.

Burn Care in the Era of Rapid Enzymatic Debridement: Challenging the Dogma that Healing Beyond 21 Days Results in Hypertrophic Scarring

Deep burns are characterized by the presence of a necrotic eschar that delays healing and results in a local and systemic inflammatory response and following healing by secondary intention: heavy scarring. Early surgical debridement followed by grafting was a major advance in deep burn care and is now the standard of care, reducing mortality and hypertrophic scarring. Eschars have alternatively been managed by non-surgical, autolytic debridement, which often results in infection-inflammation, slow epithelialization, granulation tissue formation and subsequent scarring. Studies based on these traditional approaches have demonstrated an association between delayed wound closure (beyond 21 days) and scarring. Early enzymatic debridement with NexoBrid (NXB) followed by appropriate wound care is a novel minimally invasive modality that challenges the well-accepted dictum of a high risk of hypertrophic scarring associated with wound closure that extends beyond 21 days. This is not surprising since early and selective removal of only the necrotic eschar often leaves enough viable dermis and skin appendages to allow healing by epithelialization over the dermis. In the absence of necrotic tissue, healing is similar to epithelialization of clean dermal wounds (like many donor sites) and not healing by the secondary intention that is based on granulation tissue formation and subsequent scarring. If and when granulation islands start to appear on the epithelializing dermis, they and the inflammatory response generally can be controlled by short courses (1-3 days) of topically applied low strength corticosteroid ointments minimizing the risk of hypertrophic scarring, albeit with wound closure delayed beyond the magic number of 21 days. Results from multiple studies and field experience confirm that while deep burns managed with early enzymatic debridement often require more than 21 days to reepithelialize, long-term cosmetic results are at least as good as with excision and grafting.

Pectin-Based Scaffolds for Tissue Engineering Applications

Tissue engineering (TE) is an interdisciplinary field that was introduced from the necessity of finding alternative approaches to transplantation for the treatment of damaged and diseased organs or tissues. Unlike the conventional procedures, TE aims at inducing the regeneration of injured tissues through the implantation of customized and functional engineered tissues, built on the so-called ‘scaffolds’. These provide structural support to cells and regulate the process of new tissue formation. The properties of the scaffold are essentials, and they can be controlled by varying the biomaterial formulation and the fabrication technology used to its production. Pectin is emerging as an alternative biomaterial to non-degradable and high-cost petroleum-based biopolymers commonly used in this field. It shows several promising properties including biocompatibility, biodegradability, non-toxicity and gelling capability. Pectin-based formulations can be processed through different fabrication approaches into bidimensional and three-dimensional scaffolds. This chapter aims at highlighting the potentiality in using pectin as biomaterial in the field of tissue engineering. The most representative applications of pectin in preparing scaffolds for wound healing and tissue regeneration are discussed.

Theracal lc: A boon to dentistry

TheraCal LC, the focus of this article, is a material that creates a new category of resin-modified calcium silicates (RMCS). It is a light-cured, resin-based, and highly radiopaque liner designed to release calcium to promote hard-tissue formation, and is indicated for use under direct restorative materials as a replacement to calcium hydroxide and other calcium silicate-based materials, glass ionomers, eugenol-based sedative materials, and pulp capping restoratives. TheraCal LC exhibits several properties to help maintain ideal hard-tissue health and to reduce the incidence of postoperative sensitivity. This article is aimed to review the composition, method of application, setting reaction, properties and uses of TheraCal LC. TheraCal LC is interesting and promising product, which have the potential of creating major contributions to maintaining pulp vitality.

Gelatin-Alginate Coacervates Optimized by DOE to Improve Delivery of bFGF for Wound Healing

Metabolic disorders in diabetic patients are associated with altered protein and lipid metabolism and defects in granulation tissue formation, resulting in non-healing wounds such as diabetic foot ulcers (DFU). Growth factors have essential roles in tissue re-epithelization and angiogenesis during wound healing. In this study, a complex coacervate was evaluated as an enhanced delivery system for fibroblast growth factor (bFGF) to control its release rate and protect it from proteases. Coacervates composed of gelatin Type A (GA) and sodium alginate (SA) were optimized by the Design of Experiments (DOE), with the polymer ratio and the medium’s pH as the independent variables, and turbidity, particle size, polydispersity index, and encapsulation efficiency (EE, %) as the responses. The optimized coacervate protected bFGF from trypsin digestion and showed controlled release compared with bFGF in solution or a physical mixture of GA and SA. It enhanced the viability, migration, and procollagen I C-terminal propeptide synthesis of human dermal fibroblasts in hyperglycemic conditions. In summary, the DOE approach was successfully applied to optimize bFGF GA-SA coacervates as a potential novel therapeutic modality to treat DFU.

Histometric and Histological Analysis of Bone to Screw Contact Between Metallic and Absorbable 2.0 Fixation System: A Pilot Study in Dogs

ObjectiveTo evaluate the bone/screw interface of a titanium IF system and an absorbable IF system.Materials and methodsTwelve male adult dogs were subjected to osteotomy performed between the third and fourth mandibular premolars, been divided into two groups (control or experimental side). Two miniplates were applied to fix mandible fragments. Histometric values for bone-to-screw contact (BSC), bone-to-screw distance (BSD) and histological findings were evaluated at 2 and 18 weeks.ResultsDifference in BSC were detected from absorbable and metallic monocortical group on the experimental side at 2 weeks (p = 0.0041). Larger BSDs were detected at buccal bicortical absorbable experimental sides (p = 0.0041), with larger distances detected from the vestibular side to the lingual cortical side (p < 0.0001) and on the control side at 18 weeks (p = 0.0143), having metallic group significant BSD results on the experimental side at 2 weeks (p = 0.047). Connective tissue was noted on vestibular cortical side in monocortical and bicortical absorbable screw groups. ConclusionsAbsorbable bicortical screws with splint had histometric and histological behaviors similar to metallic bicortical group at lingual cortical side.Clinical RelevanceInion absorbable bicortical screws did not promote connective tissue formation at lingual cortical side.