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Following implant placement, a soft tissue barrier will form at the healing abutment connection called peri-implant mucosa. The dimension of this anatomical structure seems to play a key role in maintaining long-term peri-implant and marginal bone level stability. In its early stages, soft tissue healing is a process involving many cellular and molecular events. Enamel matrix derivative (EMD) may improve and accelerate soft tissue wound healing and inflammatory resolution. In the present split-mouth randomized clinical trial, EMD was used to influence the early phase of soft tissue healing around dental implants placed with a single-stage approach into a completely healed ridge. A total of 60 implants were placed in 30 patients (2 implants per patient, one in the test group and one in the control group). In the test sites, EMD was administered around the healing abutment before soft tissues were sutured. Soft tissue healing index (HI) and secondary endpoints (clinical, radiographic, and patientreported outcomes) were measured. Better outcomes were recorded in patients receiving EMD for all parameters. The present results support the use of EMD to improve and accelerate soft tissue wound healing around implants. [ABSTRACT FROM AUTHOR]

Multiple adjacent gingival recessions (MAGRs) are commonly treated with autogenous grafts. However, several intra- and postsurgical complications have been described following autogenous grafts, leading clinicians to explore the use of different biomaterials to treat these conditions. The aim of the present study was to evaluate the root coverage outcomes of a novel porcine-derived acellular dermal matrix (PADM) in combination with the tunneled coronally advanced flap (TCAF) for the treatment of MAGRs. Ten patients with 33 type 1 recession defects (RT1s) were treated with PADM + TCAF. The outcomes of interest included the mean root coverage (mRC), the frequency of complete root coverage (CRC), changes in keratinized tissue width, volumetric gain at the treated sites (assessed with digital intraoral scanning), and patient-reported outcome measures. All treated sites healed uneventfully, and no complications were noted throughout the study. At 6 months, a statistically significant reduction in recession was noted at the treated sites, exhibiting an overall mRC of 89.14% ± 19.15% and a CRC of 72.7%. The average volume gain after 6 months was 26.28 ± 11.71 mm3, and the mean distance between the surface/mean thickness of the reconstructed volume (DD) was 0.63 ± 0.28 mm. The region-specific volumetric analysis revealed an overall higher linear dimensional gain at the midroot aspect (range: 0.72 to 0.78 mm, assessed 1 to 4 mm apical to the cementoenamel junction) compared to the other regions. The present study presents the clinical and volumetric outcomes of PADM + TCAF for the treatment of MAGRs. A significant amount of volumetric gain was also observed at 6 months as a result of the treatment, along with satisfactory esthetic and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To answer the following question: "Do recombinant, purified, and concentrated growth factors enhance the regenerative potential of particulate bone graft substitutes in maxillary sinus floor augmentation (MSA)" Materials and Methods: Human studies comparing histomorphometric data on new bone formation, residual graft material, and fibrous tissue ratio (outcomes of interest) following MSA procedures employing particulate bone grafts/substitutes in combination or not with growth factors were retrieved from PubMed/MEDLINE, Web of Science, Cochrane, and Scopus online databases and complemented with a hand search. Controlled studies published in English up to December 2022 and reporting on histomorphometric data expressed as volume percentage of the outcomes of interest were considered. Risk of bias was assessed, and a meta-analysis was performed to investigate the effects of supplementary growth factors on new bone formation, remaining graft particles, and fibrous tissue ratio. Results: Data were included from 613 samples in 477 patients reported in 22 publications. Meta-analysis showed that platelet-rich plasma or platelet-rich fibrin resulted in 49% more new bone formation than in control group areas (P = .004), and those areas supplemented with growth factors presented 57% less residual graft particles after healing (P < .0001). A significant (P = .03) 1.85-fold increase in connective tissue formation was noted in areas treated with recombinant human bone morphogenetic proteins (rhBMPs) after healing. Conclusions: Selective supplementary growth factors may enhance new bone formation and accelerate particulate graft turnover, while rhBMP may significantly increase connective tissue formation in MSA procedures in humans. [ABSTRACT FROM AUTHOR]

Purpose: To assess the healing process of the extraction socket and the dimensional changes that occur after alveolar ridge preservation utilizing a polylactide-co-glycolide scaffold (PLGA). Materials and Methods: The present study involved the extraction of 28 teeth from 14 patients. The total number of sockets was 28, which were divided into two groups consisting of 14 test sockets and 14 control sockets. The study group (SG) was subjected to socket preservation with a PLGA scaffold while the control group (CG) was left for spontaneous healing. The dimensions were measured before and after operation at 1, 3, and 5 mm below the alveolar crest horizontally and the height of buccolingual bone vertically. Results: According to the histologic analyses, the PLGA scaffold was resorbed within 4 months. CBCT imaging revealed a decrease in the horizontal crest dimension at three distinct coronoapical levels in SG, measuring 2.05 ± 1.05 mm at -1 mm, 1.51 ± 0.89 mm at -3 mm, and 0.92 ± 0.7 mm at -5 mm. CG showed readings of 1.22 ± 1 at -1 mm, 0.92 ± 0.67 at -3 mm, and 0.73 ± 0.69 at -5 mm. In comparison to CG, SG showed a significant reduction in horizontal losses at -1 mm. Vertical crest dimensions decreased by 1.64 ± 1.11 mm for the buccal bone height and by 1.56 ± 1.08 mm for lingual bone height in SG; in CG, the buccal and lingual bone height had mean values of 2.08 ± 1.44 mm and 1.73 ± 1.27 mm, respectively. There was no statistically significant difference observed in the vertical losses between the groups. Conclusions: Following a period of 4 months, the PLGA scaffold was completely resorbed. Based on CBCT measurements, horizontal resorption was lower than CG at -1 mm coronally. [ABSTRACT FROM AUTHOR]

Purpose: To examine the behavior and function of human gingival fibroblasts growing on healing abutments with or without laser-textured topography. Materials and Methods: Human primary gingival connective tissue fibroblasts were cultured on healing abutments with machined or laser-textured (Laser-Lok, BioHorizons) surfaces. Cellular and molecular responses were evaluated by a variety of tests, including cell density assay (WST-1), fluorescence microscopy, real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and detachment tests. Results: The machined surface showed monodirectional traces and scratches from milling, whereas the laser-textured surface showed a distinct morphology consisting of monodirectional mesoscale channels (15-µm pitch) and woven oblique microridges formed within the channels. There were no differences in initial fibroblast attachment, subsequent fibroblast proliferation, or collagen production between the machined and laser-textured surfaces. Fibroblasts growing on a laser-textured surface were found to spread in one direction along the mesochannels, while cells growing on machined surfaces tended to spread randomly. Fibroblasts on laser-textured surfaces were 1.8 times more resistant to detachment than those on machined surfaces. An adhesive glycoprotein (fibronectin) and transmembrane adhesion linker gene (integrin ß-1) were upregulated on laser-textured surfaces. Conclusions: The increased fibroblast retention, uniform growth, and increased transcription of cell adhesion proteins compellingly explain the enhanced tissue-level response to laser-created and hybrid-textured titanium surfaces. These results provide a cellular and molecular rationale for the tissue reaction to this unique surface; in addition, they support its extended use, from implants and healing abutments to diverse prosthetic components where enhanced soft tissue responses would be desirable. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical effectiveness of regenerative treatment of intrabony defects in combination with consecutive orthodontic therapy with clear aligners in stage IV (type 2) periodontitis. Method and materials: Ten patients with a total of 103 intrabony defects were analyzed after regenerative surgery using collagen-deproteinized bovine bone mineral with or without collagen membrane or enamel matrix derivative followed by orthodontic therapy with clear aligners. Changes in radiographic bone level and probing pocket depths were evaluated after 1 year (T1) and at final splinting (T2) after orthodontic tooth movement. Results: Mean radiographic bone level gain was significant, with 2.13 ± 1.64 mm at T1 and 3.02 ± 2.00 mm at T2. Mean probing pocket depth was significantly reduced from 5.40 ± 1.80 mm at baseline to 3.78 ± 1.73 mm at T1, and remained stable with 3.73 ± 1.70 mm at T2. Pocket closure (≤ 4 mm probing pocket depth) was accomplished in 76% of all defects. Tooth loss amounted to 2.9%. Conclusion: Within the limitations of the retrospective study design, the findings suggest that the interdisciplinary treatment of periodontitis stage IV by regenerative periodontal surgery and consecutive orthodontic therapy with clear aligners can lead to favorable results. [ABSTRACT FROM AUTHOR]

Successful bone augmentation relies on primary wound closure. The labial frenum is a soft tissue that connects the lip to the alveolar mucosa or gingiva. However, the frenum may exert biomechanical forces to the wound edge, causing wound instability. The aim of this study is to review the frenum composition and classifications and to understand the significance of the frenum in wound stability upon bone regeneration. Together with a manual search, an electronic search was conducted through three online databases on studies published until September 2022. A total of 300 articles were identified, and 9 studies were included in this review. Two of the included studies discovered that 35% to 37.5% of the labial frenum had muscle fibers. Other studies showed that the labial frenum was mainly composed of connective tissue with elastic fibers. There are two widely used classifications for the frenum based on its morphology and attachment position. No studies specifically evaluated the impact of the frenum on bone regeneration, but the frenum location intercorrelated with the amount of keratinized tissue, which could influence wound stability. A modified frenum classification for the edentulous ridge and a decision diagram to manage the frenum is proposed for research and evidence-based practice. [ABSTRACT FROM AUTHOR]

Purpose: To answer the following focus question: In preclinical in vivo experimental models, do oral implants placed in overdimensioned (OD) sites present greater biomechanical properties and histomorphometric parameters of osseointegration compared to implants placed in standard or undersized implant sockets? Materials and Methods: Online databases were searched for controlled animal studies reporting on OD sites up to February 2023. The relative implant-final drill discrepancy (IDD) was used to categorize the control and test groups according to surgical drilling protocol: (1) control: undersized (IDD > 0.5 mm) or standard (IDD = 0.2 to 0.5 mm); and (2) test OD: stress-free oversized (IDD = 0.0 to -0.1 mm); test GAP: friction-free oversized (IDD = -0.1 mm). Random-effects meta-analyses were performed for the outcomes of insertion and removal torque values (ITV and RTV, respectively), bone-to-implant contact (%BIC), and bone density (%BD) for short- (0 to 2 weeks), intermediate- (3 to 4 weeks), and long-term (= 5 weeks) healing periods. Results: Of the 527 records identified, 13 studies met the eligibility criteria. Histologically, the OD and GAP groups prevented ischemic necrosis and extensive bone resorption at the bone-implant interface in both the marginal cortical layer and the trabeculae. Faster and increased rates of bone formation, characterized by primary osteons and highly vascularized tissue, took place in OD sites between 1 and 5 weeks of healing. Meta-analyses indicated statistically significant benefits in favor of (1) control vs OD for short-term healing in extraoral sites, with pooled estimates (weighted mean difference) of ITV = 25.35 Ncm, %BIC = 2.10%, and %BD = 26.19%; (2) control vs OD for long-term healing in intraoral sites, with %BD = 11.69%; (3) control vs GAP for intermediate-term healing in extraoral sites, with %BD = 3.03%; and (4) control vs GAP for long-term healing in extraoral sites, with RTV = 5.57 Ncm. Conclusions: Oversized surgical preparation of the implant site does not seem to provide any additional benefit compared to standard or undersized sites regarding quantitative parameters of osseointegration. However, it does minimize marginal bone resorption and yields better-quality bone healing, despite the comparable results among different experimental animal models in the late postoperative period. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. Method and materials: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. Results: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. Conclusion: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes; however, fundamental features of these cells are poorly understood. Here we show that following spinal cord injury or stroke, 90% and 10% of border-forming astrocytes derive, respectively, from proliferating local astrocytes and oligodendrocyte progenitor cells in adult mice of both sexes. Temporal transcriptome analysis, single-nucleus RNA sequencing and immunohistochemistry show that after focal CNS injury, local mature astrocytes dedifferentiate, proliferate and become transcriptionally reprogrammed to permanently altered new states, with persisting downregulation of molecules associated with astrocyte-neuron interactions and upregulation of molecules associated with wound healing, microbial defense and interactions with stromal and immune cells. These wound repair astrocytes share morphologic and transcriptional features with perimeningeal limitans astrocytes and are the predominant source of neuroprotective borders that re-establish CNS integrity around lesions by separating neural parenchyma from stromal and immune cells as occurs throughout the healthy CNS.

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels. Using single-cell RNA sequencing, we further show that heavily crosslinked hydrogels increase inflammation and lead to the formation of a distinct macrophage subpopulation exhibiting signs of oxidative activity and cell fusion. Conversely, lightly crosslinked hydrogels are more readily taken up by macrophages and integrated within the tissue. The physical properties differentially affect macrophage and fibroblast interactions, with heavily crosslinked hydrogels promoting pro-fibrotic fibroblast activity that drives macrophage fusion through RANKL signaling. These findings suggest that tuning the physical properties of hydrogels can guide cellular responses and improve healing, offering insights for designing better biomaterials for wound treatment.

Diabetic foot ulcers (DFU) are chronic, refractory wounds caused by diabetic neuropathy, vascular disease, and bacterial infection, and have become one of the most serious and persistent complications of diabetes mellitus because of their high incidence and difficulty in healing. Its malignancy results from a complex microenvironment that includes a series of unfriendly physiological states secondary to hyperglycemia, such as recurrent infections, excessive oxidative stress, persistent inflammation, and ischemia and hypoxia. However, current common clinical treatments, such as antibiotic therapy, insulin therapy, surgical debridement, and conventional wound dressings all have drawbacks, and suboptimal outcomes exacerbate the financial and physical burdens of diabetic patients. Therefore, development of new, effective and affordable treatments for DFU represents a top priority to improve the quality of life of diabetic patients. In recent years, nanozymes-based diabetic wound therapy systems have been attracting extensive interest by integrating the unique advantages of nanomaterials and natural enzymes. Compared with natural enzymes, nanozymes possess more stable catalytic activity, lower production cost and greater maneuverability. Remarkably, many nanozymes possess multienzyme activities that can cascade multiple enzyme-catalyzed reactions simultaneously throughout the recovery process of DFU. Additionally, their favorable photothermal-acoustic properties can be exploited for further enhancement of the therapeutic effects. In this review we first describe the characteristic pathological microenvironment of DFU, then discuss the therapeutic mechanisms and applications of nanozymes in DFU healing, and finally, highlight the challenges and perspectives of nanozyme development for DFU treatment.

Finding the optimal treatment strategy to accelerate wound healing is of utmost importance, but it presents a formidable challenge owing to the intrinsic nonlinear nature of the process. We propose an adaptive closed-loop control framework that incorporates deep learning, optimal control and reinforcement learning to accelerate wound healing. By adaptively learning a linear representation of nonlinear wound healing dynamics using deep learning and interactively training a deep reinforcement learning agent for tracking the optimal signal derived from this representation without the need for intricate mathematical modelling, our approach has not only successfully reduced the wound healing time by 45.56% compared to the one without any treatment, but also demonstrates the advantages of offering a safer and more economical treatment strategy. The proposed methodology showcases a significant potential for expediting wound healing by effectively integrating perception, predictive modelling and optimal adaptive control, eliminating the need for intricate mathematical models.

Objective: Mucogingival surgery involving tissue grafts is commonly employed for cosmetic procedures like root coverage, and is increasingly applied in implant therapy to modulate peri-implant soft tissues and enhance implant survival. These procedures involve harvesting autologous connective or epithelial connective tissue, often from the palate or tuber maxillae. However, this can cause patient morbidity due to postoperative pain. Substitute materials, including animal-derived and xenografts, have been developed but lack qualities of autologous grafts. Method and materials: To address postoperative discomfort, a novel technique, named "palatal shield," using composite resin stabilized on adjacent teeth's palatal surface is proposed as an aid to donor site healing after mucogingival procedures. Two cases are reported where this technique was successfully applied. The first case involves a 53-year-old woman undergoing free gingival graft surgery for peri-implant treatment. The second case features a 58-year-old man receiving subepithelial connective tissue graft surgery for root sensitivity. Results: Ten days post surgery, both patients reported excellent postoperative comfort. The technique's effectiveness is highlighted in these cases, demonstrating its applicability in various surgical cases involving free gingival graft or connective tissue graft harvesting. Conclusion: The proposed "palatal shield" technique offers several advantages, including enhanced patient comfort, ease of application, and cost-effectiveness, making it a promising addition to mucogingival surgical procedures. [ABSTRACT FROM AUTHOR]

Vertical ridge augmentation in the anterior mandible is a technically delicate procedure that requires knowledge of some anatomical structures to reduce intra- and postoperative complications. Proper soft tissue management is one of the primary aspects to the success of these techniques, enabling tension-free primary wound closure and preventing membrane exposure. This cadaveric and clinical study provides an anatomical overview of the lingual portion of the anterior mandible. Moreover, there is a description of a novel surgical approach for release of the lingual flap that will help clinicians achieve primary closure without incurring intrasurgical complications. [ABSTRACT FROM AUTHOR]

Traditional GBR procedures have been associated with frequent complications and compromised peri-implant esthetics. Tunneling techniques have been proposed as a promising alternative in this regard. More recently, a subperiosteal minimally invasive aesthetic ridge augmentation technique (SMART) was reported to have been clinically successful in a prospective case series. This technique includes the use of a bone graft/recombinant human platelet-derived growth factor-BB combination delivered to the site by a tunneling method. However, published histologic information regarding the nature of the regenerated tissue has been limited. The current study evaluated the histologic and histomorphometric findings of four human specimens harvested at 2, 5, 9, and 14 months after ridge augmentation using the SMART method. Evaluations of the wound healing and bone regeneration sequence over time found that the ridge augmentation was the result of extensive new bone formation that progressed through the woven bone to lamellar bone stages, with remodeling of the xenogeneic graft material and replacement by patient bone. This is the first study utilizing sequential human specimens to histologically examine the chronology of wound healing following alveolar ridge augmentation. [ABSTRACT FROM AUTHOR]

Successful rehabilitation of severely atrophic, short-span edentulous ridges in esthetic regions can seldom be done without some form of vertical ridge augmentation (VRA). The best available evidence shows that guided bone regeneration procedures may present a very predictable option with reduced potential for complications compared to alternative options. The present case series presents a novel technique to achieve predictable VRA with a low complication rate using tenting screws and cross-linked resorbable membranes. A total of 10 patients (5 men, 5 women) with severe vertical defects in the esthetic zone participated in this study. Following a mean healing time of 9.3 months, the mean defect resolution was 80%, with a mean vertical bone gain of 6.2 ± 1.61 mm. Only one case presented with reduced defect resolution (50%); however, the bone gain for this case was 6 mm. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the usefulness of ridge augmentation using a customized titanium mesh (CTM) that was preformed by trimming and bending the commercial titanium mesh on a virtually reconstructed 3D acrylic resin model using clinical, radiologic, histologic, and histomorphometric analyses. Materials and Methods: This study was designed prospectively for patients who required vertical ridge augmentation using a staged approach before implant surgery. After installation of the CTM, grafting was performed using deproteinized porcine bone mineral covered with an absorbable membrane. Computed tomography was performed preoperatively and 6 months after simultaneous/staged guided bone regeneration to measure planned, reconstructed, and lacking bone volume, and the reconstruction rate was calculated based on these values. Clinical complications were also recorded, particularly the mesh exposure rate. At re-entry, the bone core was obtained using a trephine bur, and histologic and histomorphometric analyses were performed. Results: A total of 10 sites in eight patients were used for the study analysis. The mean planned bone volume was 1.15 cm3 (range: 0.78 to 1.56 cm3), mean lacking bone volume was 0.13 cm3 (range: 0 to 0.59 cm3), and mean reconstructed bone volume was 1.02 cm3 (range: 0.56 to 1.43 cm3). The exposure rate was 30% (3 out of 10 sites). The reconstruction rate was over 80%, except for one case that showed suppuration. From histomorphometric analysis, 27.52% ± 16.87% of new bone, 7.62% ± 5.19% of residual graft, and 64.86% ± 23.76% of connective tissue were observed. The core biopsy samples demonstrated different pseudoperiosteum layer appearances based on the healing stage of the augmented sites. In the premature bone, the inner osteogenic layer consisted of multiple layers of osteoblast cells with adjacent large blood vessels. However, in the mature augmented site, there was no specific inner osteogenic layer, and the outer fibrous layer was dominant. Conclusions: The fabrication of CTM based on the application of the 3D-printing technique makes vertical ridge augmentation easier and can reduce complications and achieve target bone acquisition. In addition, it is expected that quantitative analysis of the pseudoperiosteum layer will be facilitated using the CTM. [ABSTRACT FROM AUTHOR]

Purpose: The present study describes a new presurgical soft tissue technique in oral/maxillary bone reconstructive surgery for reducing the risk of soft tissue dehiscence and its related complications. Materials and Methods: Ten consecutive patients with Cawood and Howell type V atrophy were scheduled for CAD/CAM titanium mesh bone reconstructive surgery after applying the vascular delay technique 21 days before regenerative surgery. The surgical and healing complications were clinically assessed at nine time points, ranging from the time of bone regenerative surgery to 9 months after surgery. Surgical complications included flap damage and neurologic and vascular complications. Healing complications were subdivided into four classes. These classes comprised Class I: small membrane exposure (= 3 mm) without purulent exudate; Class II: large membrane exposure (> 3 mm) without purulent exudate; Class III: membrane exposure with purulent exudate; and Class IV: abscess formation without membrane. Results: The study sample included seven men and three women (mean age: 48.2 ± 3.5 years) with seven mandibular cases and three maxillary cases. The defect length ranged from three to six teeth, with a mean mesiodistal distance of 29.9 ± 8.5 mm and a mean volume augmentation of 2.03 ± 0.9 cm3. There were no surgical complications. One patient presented a Class I healing complication that did not affect the regeneration outcome. Conclusions: The vascular delay technique appears to reduce the risk of soft tissue dehiscence and exposure in bone regenerative surgery, though randomized studies involving larger samples and longer follow-up periods are needed in order to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Wound healing is a complex physiological process that requires precise control and modulation of many parameters. Therapeutic ion and biomolecule delivery has the capability to regulate the wound healing process beneficially. However, achieving controlled delivery through a compact device with the ability to deliver multiple therapeutic species can be a challenge. Bioelectronic devices have emerged as a promising approach for therapeutic delivery. Here, we present a pro-reparative bioelectronic device designed to deliver ions and biomolecules for wound healing applications. The device incorporates ion pumps for the targeted delivery of H+ and zolmitriptan to the wound site. In vivo studies using a mouse model further validated the device's potential for modulating the wound environment via H+ delivery that decreased M1/M2 macrophage ratios. Overall, this bioelectronic ion pump demonstrates potential for accelerating wound healing via targeted and controlled delivery of therapeutic agents to wounds. Continued optimization and development of this device could not only lead to significant advancements in tissue repair and wound healing strategies but also reveal new physiological information about the dynamic wound environment.

Minimally invasive nonsurgical treatment (MINST) aims to remove an etiology with minimal damage to the healthy periodontium and provide the ideal healing environment. This case series introduces the novel protocol of laser-assisted MINST (LAMINST), combining minimally invasive surgery with a dental laser. A total of 25 patients (32 teeth) with advanced periodontal disease were enrolled and received periodontal treatment by following the LAMINST protocol. Probing depth (PD), recession, clinical attachment level (CAL), bleeding on probing (BOP), plaque presence, and site mobility were evaluated preoperatively and at 6 months. Based on the periodontal evaluations, all cases were diagnosed as stage III grade C periodontitis. Six months after LAMINST, the average PD reduction was 4.44 mm and CAL improved by 4.38 mm. Baseline mobility scores of 1 (6 teeth), 2 (9 teeth), and 3 (3 teeth) decreased to 1 (5 teeth) or 0 (13 teeth). The initial prognoses of 5 (hopeless; 15 teeth), 4 (questionable; 13 teeth), and 3 (poor; 4 teeth), improved to 4 (5 teeth), 3 (12 teeth), 2 (fair; 13 teeth), and 1 (good; 2 teeth). The number of BOP sites reduced from 179 to 12, and the number of plaque sites reduced from 173 to 9. All clinical parameters were improved after LAMINST. The application of LAMINST may overcome the traditional limitations of nonsurgical treatment, such as poor accessibility. [ABSTRACT FROM AUTHOR]

Diode lasers are increasingly being utilized as an alternative to conventional soft tissue surgery. Diode lasers originally referred to wavelengths ranging from 810 to 980 nm, but a visible diode laser with a 445-nm wavelength has emerged as an additional wavelength for soft tissue surgery. The goal of this case series was to demonstrate the clinical results of both visible and nearinfrared (NIR) wavelengths when utilized for stage-two implant surgery. Ten patients with 23 implants were treated at Stony Brook University, Department of Periodontics and Endodontics and Faculty Practice, for implant uncovering using both visible and nonvisible (NIR) diode lasers. The uncovering was performed utilizing 445-, 970-, and 980-nm wavelengths at a power setting of 2 W in either continuous or pulsed modes. The fiberoptic tips were initiated using blue articulating paper. Either topical benzocaine or infiltration anesthesia was utilized prior to soft tissue removal with the initiated tip. All patients healed uneventfully without any postoperative complications. Visible and NIR diode lasers provide an alternative and safe method to uncover submerged implants at stage-two surgery. [ABSTRACT FROM AUTHOR]

This study evaluated the clinical efficacy of the coronally advanced lingual flap (CALF) technique in terms of the extent of lingual and buccal flap advancement, the maintenance of primary wound closure, and safety in comparison to buccal flap advancement alone during horizontal ridge augmentation in the posterior mandible. A total of 14 patients were randomly allocated to two different groups: buccal flap advancement without the CALF technique (control), referred to as the NO-CALF group, and buccal flap advancement with the CALF technique (test), referred to as the CALF group. Wound healing was monitored weekly for the first 4 weeks, then at 2, 4, 6, and 9 months postoperatively for any sod tissue dehiscence (titanium mesh [TM] exposure) along the incision line. The extent of lingual and buccal flap advancement was measured, and any intraoperative and postoperative CALF-related complications were reported. The difference between groups was statistically significant (P < .0001) in terms of (1) TM exposure: 83.3% of cases in the NO-CALF group showed early Class П exposures, whereas the CALF group showed no exposure; (2) mean lingual flap advancement: 3.9 ± 1.1 mm and 14.4 ± 3.8 mm for the NO-CALF and CALF groups, respectively; and (3) mean buccal flap advancement: 15.8 ± 2.1 mm and 10.5 ± 1.4 mm for the NO-CALF and CALF groups, respectively. There were no reported complications related to the CALF technique. Tension-free primary wound closure was facilitated and maintained during the healing period by applying the CALF technique, which is a reliable technique to safely advance the lingual flap coronally. [ABSTRACT FROM AUTHOR]

Currently, the incision design for periodontal and implant surgeries is mainly based on the surgeon's personal preference. The primary aim of this study is to review the intricate periodontal microvascular system and to illustrate the potential impact of commonly applied flap designs on the integrity of this system. A complete literature electronic search resulted in 37 relevant articles. The maxillary, facial, and lingual arteries supply the microvasculature system, including the supraperiosteal, intraligamental, and intraosseous arterioles. These arterioles have their own territories yet are extensively interconnected. The impact of common papilla management techniques are discussed, including tunneling; papilla base, incision, and preservation; and flap-releasing incisions. Flap design can impact reperfusion and blood inflow in the early healing phase, which eventually influences wound closure probability, healing speed, surgical predictability, tissue volume change, and postoperative morbidity. Future studies on the three-dimensional distribution of microvasculature and clinical impact of various flap designs on tissue reperfusion can lead to evidence-based incision selection and improved wound-healing outcomes. [ABSTRACT FROM AUTHOR]

Impaired healing wounds do not proceed through the normal healing processes in a timely and orderly manner, and while they do eventually heal, their healing is not optimal. Chronic wounds, on the other hand, remain unhealed for weeks or months. In the US alone, chronic wounds impact ~8.5 million people and cost ~USD 28-90 billion per year, not accounting for the psychological and physical pain and emotional suffering that patients endure. These numbers are only expected to rise in the future as the elderly populations and the incidence of comorbidities such as diabetes, hypertension, and obesity increase. Over the last few decades, scientists have used a variety of approaches to treat chronic wounds, but unfortunately, to date, there is no effective treatment. Indeed, while there are thousands of drugs to combat cancer, there is only one single drug approved for the treatment of chronic wounds. This is in part because wound healing is a very complex process involving many phases that must occur sequentially and in a timely manner. Furthermore, models that fully mimic human chronic wounds have not been developed. In this review, we assess various models currently being used to study the biology of impaired healing and chronic non-healing wounds. Among them, this paper also highlights one model which shows significant promise; this model uses aged and obese db/db-/- mice and the chronic wounds that develop show characteristics of human chronic wounds that include increased oxidative stress, chronic inflammation, damaged microvasculature, abnormal collagen matrix deposition, a lack of re-epithelialization, and the spontaneous development of multi-bacterial biofilm. We also discuss how important it is that we continue to develop chronic wound models that more closely mimic those of humans and that can be used to test potential treatments to heal chronic wounds.

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.

Objective of the study is to assess the effects of wound healing with a commercially available light emitting diode (LED) photo biomodulation (PBM) device that emits three wavelengths (465, 640 and 880nm) after ablative fractional laser (AFL) treatment to healthy skin on the bilateral inner biceps. We conducted a prospective intraindividual randomized controlled study with 25 volunteers. AFL treatment was performed on healthy skin of the bilateral inner biceps. Subjects applied the LED light device for 30 min to the assigned bicep 3 times a week over 4 weeks, beginning on day 0. Subjects were followed up on days 2, 4, 6, 9, 13, 20 and 27 for treatment with the PBM device, clinical digital photography of the test and control sites, and in-person subject assessment, with follow ups on days 34 and 55 for clinical photography and assessment. Three blinded evaluators were asked to determine which bicep healed faster between day 0 to day 13. Pain, discomfort, and itch were also assessed. The three blinded evaluators chose the treatment arm as the faster healed arm in greater than 50% of the images, although the results were not statistically significant. There was no statistically significant difference between test and control arms in terms of pain, discomfort and itch. In conclusion, PBM therapy has the potential to improve wound healing. In this study, a three wavelength PBM device resulted in some subjects achieving faster healing after AFL but the results were not statistically significant.

The ability to deliver drugs with precise dosages at specific time points can significantly improve disease treatment while reducing side effects. Drug encapsulation for gradual delivery has opened the doors for a superior treatment regimen. To expand on this ability, programming bioelectronic devices to deliver small molecules enables ad-hoc personalized therapeutic profiles that are more complex than gradual release. Here, a wearable bioelectronic device with an integrated electrophoretic ion pump that affords on-demand drug delivery with precise dose control is introduced. Delivery of fluoxetine to wounds in mice result in a 27.2% decrease in the macrophage ratio (M1/M2) and a 39.9% increase in re-epithelialization, indicating a shorter inflammatory phase and faster overall healing. Programmable drug delivery using wearable bioelectronics in wounds introduces a broadly applicable strategy for the long-term delivery of a prescribed treatment regimen with minimal external intervention.

In this study, a wound-healing membrane was fabricated based on carboxymethyl cellulose (CMC) and polyethylene glycol (PEG) containing curcumin (Cur) and bromelain (Br). Citric acid (CA) was used as a cross-linking agent. This membrane showed an ideal degree of swelling, which was significantly dependent on the concentration and duration of cross-linked CA. The chemical characterization showed the CA cross-linker mechanism was more associated with chemical reactions with CMC carboxyl groups, and PEG hydroxyl groups played an important role in forming a hybrid polymer network. It greatly enhanced mechanical and adhesive properties, so the stress strength was improved from 29.4 to 38.52 Mpa. The hydrophilicity of the membrane surface according to the water contact angle assay showed the membrane surface is suitable for adhesion, growth, migration, and proliferation of skin cells. The drug delivery assay demonstrated that the Br and Cur were released during 48 h, but the Br followed the burst release in comparison with Cur. Antibacterial properties showed that CMC/PEG-Cur/Br have ideal antibacterial properties for preventing the growth of bacteria. In summary, the engineered CMC/PEG containing Cur/Br films with desired cell viability properties and antibacterial activity can potentially improve and accelerate skin regeneration for chronic wound healing. Highlights * Hydrogel film was prepared based on carboxymethyl cellulose (CMC), polyethylene glycol (PEG), and citric acid as cross-linking agent. * CMC/PEG film were induced controlling curcumin (Cur) and bromelain (Br) release for wound healing process. * CMC/PEG film revealed a wide range of physiochemical, mechanical, adhesion, and biological properties behavior. * Incorporation of Cur and Br promoted in vitro biocompatibility, L-929 cells attachments, and cell migration. KEYWORDS antibacterial properties, bromelain, carboxymethyl cellulose, curcumin, drug delivery, polyethylene glycol, wound dressing, 1 | INTRODUCTION As the largest human tissue, the skin serves a crucial role as a barrier against infection. (1) Due to an incomplete physical barrier and exposed subcutaneous tissue, [...]

Objective: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing/regeneration in intrabony defects. Method and mater-ials: Intrabony defects were surgically created in the mandible of three minipigs. Twelve defects were randomly treated with either rAmelX and carrier (test group) or with the carrier only (control group). At 3 months following reconstructive surgery, the animals were euthanized, and the tissues histologically processed. Thereafter, descriptive histology, histometry, and statistical analyses were performed. Results: Postoperative clinical healing was uneventful. At the defect level, no adverse reactions (eg, suppuration, abscess formation, unusual inflammatory reaction) were observed with a good biocompatibility of the tested products. The test group yielded higher values for new cementum formation (4.81 ± 1.17 mm) compared to the control group (4.39 ± 1.71 mm) without reaching statistical significance (P= .937). Moreover, regrowth of new bone was greater in the test compared to the control group (3.51 mm and 2.97 mm, respectively, P = .309). Conclusions: The present results provided for the first-time histologic evidence for periodontal regeneration following the use of rAmelX in intrabony defects, thus pointing to the potential of this novel recombinant amelogenin as a possible alternative to regenerative materials from animal origins. [ABSTRACT FROM AUTHOR]

Xenogeneic-derived biomaterials are among the most routinely employed bone substitutes for immediate grafting of extraction sites as a modality of alveolar ridge preservation (ARP). The deproteinized bovine bone material is widely used and documented around the world. The present pilot clinical trial evaluated and compared the clinical and morphologic alterations of extraction sites after ARP using two commercially available yet differently processed bovine bone grafts. A total of 20 adjacent extraction sites in 10 patients were included. All sites received the exact same ARP therapy except for the type of bovine bone graft, which was randomly assigned between two adjacent extraction sockets in 10 patients (Group A received Bio-Oss particles and Group B received Cerabone particles). At all sites, healing was monitored at the time of surgery and at 1, 2, 3, and 4 months postoperative. All of the augmented extraction sites achieved successful implant therapy regardless of the bone graft material used for ARP. Six weeks after implant placement, second-stage/uncovering procedures were performed without complications. Intergroup comparisons of the crestal gingival healing process (CGHP), mean transversal crestal ridge resorption (MTRR), and mean implant primary stability (MIPS) were in favor of Group A sites (treatment with Bio-Oss particles). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the peri-implant outcomes of customized healing abutments (CstHA) placed on dental implants inserted in fresh tooth extraction sockets. Materials and Methods: The study was registered on PROSPERO: CRD42022304320. A systematic search in PubMed, Scopus, and Web of Science was conducted between April 2022 and October 2022 to identify clinical studies involving immediate implant surgery associated with CstHA placement. The Joanna Briggs Institute Critical Appraisal and RoB2 tool were performed for the risk of bias analysis. Results: A total of 12 studies were included, most of them with low risk of bias. Four studies compared CstHA vs conventional healing abutments (CnvtHA), two compared CstHA vs cover screw and collagen matrix (CMa), and six were clinical case series. For the CstHA vs CnvtHA comparison, favorable results were observed for CstHA considering papilla maintenance and probing depth, yet the mean marginal bone level was statistically similar between CstHA and CnvtHA. CstHA showed advantages when compared to CMa for total bone volume, papilla height, and midfacial mucosa maintenance. Significantly less horizonal bone loss was reported when using CstHA compared with CMa. Horizontal and vertical bone loss was observed in a few (or no) sites in the case series using CstHA. Conclusions: CstHA provides favorable peri-implant response because in general it does not result in a significant loss of soft and hard tissues. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of split-thickness labial eversion periosteoplasty (EPP) for soft tissue closure in horizontal ridge augmentation of posterior mandibular regions using a bone shell onlay grafting technique. Materials and Methods: Sixteen patients (12 female and 4 male; mean age: 46.2 ± 8.7 years) with 18 horizontal bone defects in posterior mandibular regions were included for lateral onlay bone grafting using the bone shell technique. After lateral bone augmentation, the EPP was used for soft tissue closure and was prospectively followed up for wound healing efficacy using a modified scoring index. The scoring index included dichotomous (yes: 0 / no: 1) evaluation of the following items: (1) bleeding on palpation or spontaneously, (2) tissue color difference, (3) presence of hematoma, (4) presence of granulation tissue, (5) incomplete incision margin closure, (6) dehiscence with visible augmentation material, (7) presence of exudation, and (8) presence of suppuration. In addition, a visual analog scale (VAS) was used to quantify and record the amount of pain and swelling (0 = no pain/swelling and 5 = severe pain/swelling); VAS scores of 0, 1, and 2 were rated as 1 in the dichotomous scoring index, and VAS scores of 3, 4, and 5 were rated as 0. A summarized wound healing score consisting of all 10 items was assessed at days 2, 7, and 14 and at months 1 and 4 postoperatively, including a comparison of the follow-up evaluations. Results: The summarized healing score increased significantly (P < .01) between day 2 (score: 6.6 ± 1.1) and day 7 (score: 8.9 ± 1.0) but showed little difference between day 14 (score: 9.6 ± 0.6) and the 1- and 4-month follow-ups (score: 10.0 ± 0). There was no wound dehiscence and no incomplete incision margin adaptation. For the individual parameters evaluated, bleeding on palpation, hematoma, and exudation were the most frequent side effects at day 2 at 50%, 100%, and 22.2%, respectively, and at day 7 at 16.7%, 55.6%, and 22.2%, respectively. The average pain score and the swelling/edema score were initially 4.0 ± 0 and 3.0 ± 0.77 on day 2, with a significant decrease (P < .001) by day 7 (pain: 2.0 ± 0; edema/swelling: 2.0 ± 0.59) and day 14 (pain: 1.0 ± 0.42; edema/swelling: 2.0 ± 0.79) and complete absence (score: 0) at months 1 and 4. Conclusions: Labial split-thickness EPP facilitates flap advancement and enables tight soft tissue coverage in large horizontal posterior mandibular bone augmentations as a result of offset double-layer wound closure. Although this procedure is shown to be surgically demanding, the postoperative complication rate may be reduced significantly. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) has been shown to be beneficial in various medical fields such as wound healing, oncology or dentistry. A prominent effect induced by CAP is the boost of microcirculation in human skin tissue. Being a complex cocktail of physical and chemically reactive components, the mechanisms by which CAP enhances microcirculation still remain unclear. Thus, this study aims to identify relevant CAP components involved in stimulation of dermal microcirculation. In a comparative approach, the application of the same CAP source was modified in such a way that three different treatment modalities could be realized, each with a characteristic composition of electrical current flow and concentration of reactive species. Microcirculation parameters oxygen saturation (StO2), tissue hemoglobin index, near-infrared perfusion index and tissue water index were recorded before and after each treatment on the lateral proximal left arm of 10 healthy volunteers by means of hyperspectral imaging. The maximum microcirculatory response to CAP was observed when all components were allowed to interact with skin tissue (standard treatment). In contrast, no upregulation was found as soon as electric currents and fields had been removed from the effective component spectrum. Application of the CAP source at reduced concentrations of reactive species compared to standard treatment led to significant but less pronounced enhancement of dermal microcirculation. The findings of this study indicate that a synergistic interplay of all CAP components promotes microcirculation in dermal tissue most effectively. Moreover, the findings support the hypothesis that electric currents and fields play a key role in enabling microcirculation boost whereas availability of reactive species in the gas phase is associated with the intensity of the tissue response to CAP treatment. [ABSTRACT FROM AUTHOR]

Chronic wound healing is a class of diseases influenced by multiple complex factors, causing severe psychological and physiological impact on patients. It is an intractable clinical challenge and its possible mechanisms are not yet clear. It has been proven that adipose stem cell-derived exosomes (ADSC-Exos) can promote wound healing and inhibit scar formation by regulating inflammation, promoting cell proliferation, migration, and angiogenesis, regulating matrix remodeling, which provides a new approach for wound healing through biological treatment. This review focuses on the mechanism, treatment, and administration methods of ADSC-Exos in wound healing, providing a comprehensive understanding the mechanisms of ADSC-Exos on wound healing. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Hydrogel dressings are emerging as a promising option for the treatment of chronic wounds due to their tailorable functional properties, which can accelerate the healing. These properties can be improved by the addition of fillers such as bioactive glasses (BGs), and among these, mesoporous glasses doped with cerium (Ce-MBGs) also loaded with polyphenols (Ce-MBGs-POLY) are of interest for their antioxidant properties and dissolution behavior. Here we report the synthesis and characterization of stable hydrogels with high water content and swelling ratio (80 %) containing Ce-MBGs or Ce-MBGs-POLY. These hydrogels show a fast and significant release of ions aimed at stimulating cellular functions and retain the excellent antioxidant properties of the fillers. The new composites are thus promising starting points for the development of injectable hydrogels for chronic wound healing. [ABSTRACT FROM AUTHOR]

Composite electrospun nanofibers based on silk fibroin (SF), aminated reduced graphene oxide (NH2rGO), and oxidized-cellulose nanocrystals (AD-CNCs) were designed to promote the healing process by electrical conductivity. In this respect, CNCs were produced from cotton cellulose and oxidized in the presence of sodium periodate, and reduced GO was synthesized and functionalized with amine with p-anthranilic acid via an esterification reaction. Then the crosslink was prepared by the Schiff-base reaction between oxidized CNCs and NH2rGO. Electrospun nanofibers were prepared from silk fibroin, previously prepared from Bombyx Mori cocoons, AD-CNCs, and different ratios of NH2rGO. The SF/AD-CNCs/NH2rGO nanofibrous scaffold presented multiple propitious characteristics for cell proliferation and wound dressing including low cytotoxicity, a hydrophilic surface, thermal stability, and degradability. The physicochemical evaluations showed that with increasing the NH2rGO content, hydrophilicity and electroconductivity of nanofibers increased. The SF/AD-CNCs/NH2rGO biodegradable conductive scaffold with 2.5% NH2rGO content showed favorable nanofibrous structure, supporting and stimulating fibroblast cell proliferation and attachment. The SF/AD-CNCs/NH2rGO nanofibrous scaffold demonstrates the application potential in wound healing management. [ABSTRACT FROM AUTHOR]

Collagen derived from freshwater fish scales is a potential material for hemostatic and wound healing. 3D printing method is an environmentally friendly technique to geometrically‐controlled samples and is widely applied to prepare collagen‐based materials. This work aims to compare the advantages of preparation methods for hemostatic materials based on collagen, in which, the traditional method, solution will be compared with the modern method, 3D printing. Collagen in gel form was crosslinked with glutaraldehyde and was first time modified with ginsenoside Rb1 and Camellia chrysantha polyphenols. The characteristics of biomaterial samples, including functional groups, morphology, and element composition of samples have been assessed using infrared spectroscopy, energy‐dispersive x‐ray, field emission scanning electron microscopy. The swelling degree and hemostatic ability of biomaterial samples prepared according to two methods would be tested. The antibacterial, anti‐inflammatory tests, and in vivo test on mice were carried out on these biomaterials. The findings confirmed that the 3D printing method with direct ink writing technique is more suitable for the preparation of hemostatic collagen‐based membrane than the solution method. The time to hemostasis when using collagen‐based membrane was found to be 104.0 ± 16.7 s. Moreover, the collagen‐based biomaterials also have anti‐inflammatory and antibacterial activity. This opens potential applications of the biomaterials from fish scale collagen in practice. [ABSTRACT FROM AUTHOR]