Healing Phase Research Articles

Macrophages: Key players in diabetic wound healing

In this editorial, we discuss the article by Wen et al published. Diabetic foot ulcers are prevalent and serious complications of diabetes, significantly impacting patients’ quality of life and often leading to disability or death, thereby placing a heavy burden on society. Effective diabetic wound healing is hindered by an imbalance in macrophage polarization; many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which is crucial for tissue remodelling and repair. The wound healing process is both dynamic and complex. Healthy M1 macrophages, which have strong phagocytic abilities, are vital during the inflammatory phase of diabetic wound healing. However, the failure to transition to M2 macrophages during the proliferative phase hinders wound healing. We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase, thereby enhancing the overall healing process.

Systemic Lipid Metabolism Dysregulation as a Possible Driving Force of Fracture Non-Unions?

Introduction: Non-unions are fractures that do not heal properly, resulting in a false joint formation at the fracture site. This condition leads to major health issues and imposes a burden on national healthcare systems. The etiology of non-unions is still not fully understood; therefore, we aimed to identify potential systemic factors that may contribute to their formation. Materials and methods: We conducted a cross-sectional concomitant proteomic and metabolomic pilot study of blood plasma in patients with non-unions (N = 11) and compared them with patients with bone fracture in the normal active healing phase (N = 12). Results: We found five significantly upregulated proteins in the non-union group: immunoglobulin heavy variable 3–74, immunoglobulin lambda variable 2–18, low-density lipoprotein receptor-related protein 4, zinc-alpha-2-glycoprotein, and serum amyloid A-1 protein; and we found one downregulated protein: cystatin-C. The metabolomic study found differences in alanine, aspartate and glutamate metabolism pathways between two groups. Conclusions: The combined results of proteomic and metabolomic analyses suggest that the dysregulation of lipid metabolism may contribute to non-union formation.

Conventional Versus Regenerative Methods for Wound Healing: A Comparative Experimental Study on a Sheep Model

Background and Objectives: Wound healing is a complex process involving cellular, anatomical, and functional repair, often hindered in chronic wounds associated with diseases like diabetes and vascular disorders. This study investigated the efficacy of conventional and regenerative wound healing approaches in a sheep surgical wound model. Materials and Methods: Six female Bergamasca sheep underwent five full-thickness skin lesions treated with various methods: sterile gauze (control), chlorhexidine, sodium hypochlorite, micronized dermis system application, and dermal matrix. Wound healing progression was monitored over 42 days through wound dimension measurements, exudate analysis, and histopathological evaluations. Results: The results indicated that all wounds healed completely by day 42, with significant reductions in wound size and exudate over time. Notably, Micronized dermis system application and dermal matrix treatments showed a faster evolution in exudate characteristics and improved collagen reorganization compared to other treatments. Histological analysis revealed earlier neovascularization and better reconstitution of hair follicles in these groups. Despite the lack of significant differences in healing time, both regenerative approaches enhanced wound healing phases, contributing to exudate control, angiogenesis promotion, and reduced scar formation. Conclusions: The findings suggest that while micronized dermis system application and dermal matrix do not accelerate acute wound healing compared to conventional methods, they offer potential benefits in managing exudate and improving tissue regeneration, warranting further investigation in chronic wound scenarios.

Effect of sleep quality on wound healing among patients undergoing emergency laparotomy: an observational study.

To study the association between sleep-quality, total sleep duration and wound-healing among adult patients having good sleep-quality at the time of admission in hospital, undergoing laparotomy for various reasons. In this observational study , consecutive adult subjects undergoing emergency laparotomy were followed up until the eighth postoperative day. The primary outcome (wound healing) was assessed using the Southampton Wound Grading System. Sleep quality (assessed by the single item sleep quality scale) was the primary predictor. Pain was assessed using visual analogue pain scale. We studied the effect of postoperative sleep quality on wound healing on postoperative day 8. Secondary analyses assessed the effect of total sleep time, severity of pain and markers of systemic inflammation on wound healing. In this study 110 participants were included. The average age of participants was 41.7±16.2 years. On postoperative day 8, 34.5% rated their sleep quality as "poor to fair" and rest as "good". Postoperative poor sleep quality was associated with impaired wound healing, starting from third postoperative day (P<0.001 for each subsequent day). Multiple logistic regression was overall significant (χ2= 118.40; df=9; P<0.001), classified 92.7% cases correctly and explained 88% variance to the outcome. This model showed that shorter total-sleep-time (P=0.009), higher total leukocyte count (P=0.005), presence of comorbidities (P=0.01) and poor sleep quality during the postoperative week (OR=78.14; P=0.005) increased odds for impaired healing of wound. Poor sleep quality during the healing phase is associated with wound complications, a surrogate marker of impaired wound healing.

Nanoparticle-Based Therapeutics for Enhanced Burn Wound Healing: A Comprehensive Review.

Burn wounds pose intricate clinical challenges due to their severity and high risk of complications, demanding advanced therapeutic strategies beyond conventional treatments. This review discusses the application of nanoparticle-based therapies for optimizing burn wound healing. We explore the critical phases of burn wound healing, including inflammation, proliferation, and remodeling, while summarizing key nanoparticle-based strategies that influence these processes to optimize healing. Various nanoparticles, such as metal-based, polymer-based, and extracellular vesicles, are evaluated for their distinctive properties and mechanisms of action, including antimicrobial, anti-inflammatory, and regenerative effects. Future directions are highlighted, focusing on personalized therapies and the integration of sophisticated drug delivery systems, emphasizing the transformative potential of nanoparticles in enhancing burn wound treatment.

Outcome of Locking Plate Fixation Adjunctive to Intramedullary Rodding in Osteogenesis Imperfecta Patients.

An intramedullary rodding is the preferred fixation method in limb stabilization of OI patients. However, the intramedullary rod may not provide adequate fixation and rotational stability, especially in adolescents and adults. The incorporation of adjunctive plate fixation alongside intramedullary rodding has been introduced to enhance this stability, although its complications remain insufficiently understood. The goal of this study was to explore the outcomes of adjunctive plating in conjunction with intramedullary rodding for limb stabilization in OI patients, emphasizing the complications related to the plates during the healing phase and following plate removal. This retrospective study examined 74 limb segments from 45 patients with OI who underwent intramedullary rodding and adjunctive plating from 2008 to 2022. Criteria for inclusion comprised surgical treatment followed by a minimum of 2 years of follow-up or complication before that time point. The need for adjunctive plating arose from inadequate fixation, rotational instability, and persistent cortical gaps with intramedullary rodding alone. Medical records and follow-up radiographs were reviewed to assess the healing of the target lesion and any complications. The study encompassed 30 males and 15 females, ranging in age from 4 to 38 years, with 51 femoral and 23 tibial segments receiving treatment. Union was successfully achieved in 63 cases (85.3%), with an average union time of 14.4 months. Plates were subsequently removed in 62 cases after an average duration of 18.0 months. Before union, 11 revision surgeries were performed in 4 peri-implant fractures, 1 screw pull-out, and 6 failure of union. One sustained peri-implant fracture after the union. Following the removal of plates, complications included 10 refractures at screw sites, 3 progressive angulations at the previously targeted lesions, and 1 osteomyelitis. Kaplan-Meier analysis revealed that half of the refractures occurred within 1.8 years postplate removal. The overall complication showed borderline significance (P=0.056) among age groups. All the plate-related complications occurred at the diaphyseal, unicortical screws. Plate fixation, when used as an adjunct to intramedullary rodding, effectively stabilizes limbs in OI patients when intramedullary rods alone are inadequate. Nevertheless, given the significant risks associated with plate-related complications, adjunctive plating should be employed selectively only in instances where the union is unlikely to be achieved with intramedullary rodding alone. Level IV-case series.

The role of neuropeptides in cutaneous wound healing: a focus on mechanisms and neuropeptide-derived treatments.

An extensive network of cutaneous nerves, neuropeptides, and specific receptors richly innervates the skin and influences a variety of physiological and pathological processes. The sensory and autonomic nerve fibers secrete a variety of neuropeptides that are essential to the different phases of wound healing. In addition to initiating a neurogenic inflammatory response in the early stages of healing, neuropeptides also control wound healing by influencing immune cells, repair cells, and the growth factor network. However, the precise mechanism by which they accomplish these roles in the context of cutaneous wound healing is still unknown. Investigating the mechanisms of action of neuropeptides in wound healing and potential therapeutic applications is therefore urgently necessary. The present review discusses the process of wound healing, types of neuropeptides, potential mechanisms underlying the role of neuropeptides in cutaneous wound healing, as well as some neuropeptide-derived treatment strategies, such as hydrogels, new dressings, electro stimulation, and skin-derived precursors. Future in-depth mechanistic studies of neuropeptides in cutaneous wound healing may provide opportunities to develop therapeutic technologies that harness the roles of neuropeptides in the wound healing process.

‘Implant Stability’ is the Pivotal for the Success of Implant Treatment – A Narrative Review

The capacity of a dental implant to stay firmly attached in the jawbone following placement is referred to as implant stability. Long-term functionality and the effectiveness of implant osseointegration—the process by which the implant fuses with the bone—rely on it. Dental implants can be tested for stability using a variety of diagnostic tools. These tools assist medical professionals in evaluating the primary stability of the implant—which occurs right after implantation—and secondary stability—which occurs during the healing phase and after osseointegration. Precise evaluation of stability is necessary to establish suitable loading procedures and guarantee the implant's success. This narrative review aims to discuss various stability testing methods using in implant practice, their advantages and different equipment/instruments using for the implant stability assessment.

New titanium mesh design method in customized bone regeneration of the jaws: preliminary study on a sample of 11 patients

The aim of this study is 1) to present a new method of virtually-designed custom made scaffolds to be employed in customized bone regeneration (CBR) for segmental jaw atrophies and 2) to evaluate long-term clinical results in terms of bone regeneration success and implant rehabilitation success. A total of 11 patients with edentulousness and bone atrophy in a localized area of the mandible or the maxilla were recruited for the study. To fulfill the research inquiries, CT images of the pre-regeneration mandibular or maxillary arch of each patient were collected. A dedicated Mevislab 2.4 software was employed to virtually design custom bone regeneration meshes designed to fit the atrophic sector of each patient's mandible or maxilla. Subsequently, a second Meshmixer software was used to refine the margins of each of the designed meshes. All patients underwent oral surgery, during which a mixture of autologous and heterologous bone in a 1:1 proportion was grafted into the atrophic site, a custom-made mesh was placed, and a resorbable membrane was inserted. The mesh was removed after this procedure, and implant rehabilitation was performed. All patients underwent the bone regeneration procedure, with eight undergoing titanium mesh removal. A total of seven patients completed implant rehabilitation. Average horizontal bone augmentation was 3.525 ± 1.36 mm; average vertical bone augmentation was 4.45 ± 2.22 mm. Implant survival was 92.85%. During the healing phase, complications occurred in 9.09% of patients. The use of dedicated software, Mevislab 2.4 and Meshmixer, for titanium mesh design is an accurate, predictable, effective, and quick-to-use method. The learning curve for design is uncomplicated and rapid. Mesh exposure does not necessarily lead to bone graft failure; this complication can be treated by chlorhexidine aids.

L. plantarum UBLP-40 Versus the Combined Formula of L. rhamnosus UBLP-58 and B. longum UBBL-64 in Excisional Wound Healing: A Cellular Perspective

Introduction: The utilization of probiotics in enhancing the active healing of skin wounds represents a burgeoning trend in contemporary medicine. Previous research has extensively explored wound healing mechanisms involving the strains of Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum. This study seeks to compare and interpret cellular findings derived from immunohistochemical and pathological applications. Methods: Three groups (the control, Lactiplantibacillus plantarum (RO1) group, and Lacticaseibacillus rhamnosus and Bifidobacterium longum (PRO2) group) underwent histological analysis, and microscopic cell counting were employed, offering insights into dynamic changes among neutrophils, lymphocytes, plasmacytes, mast cells, fibroblasts, and newly formed vessels across distinct treatment groups and temporal intervals. Results: The neutrophil count was found to be elevated in PRO2 on day 2, while the same group resulted in the highest decline on day 15. The number of fibroblasts peaked on day 4 for the PRO1 group, compared to the other two groups, which peaked on day 8. The lymphocyte count was the highest in the control group, while they peaked on day 4 in PRO2. The mast cells and plasmacytes were variable and sparse among all groups and time frames. Neovascularization was promoted by PRO1 and PRO2 groups on day 4 and remained high on day 8 for PRO2. Conclusions: Probiotic strains can be beneficial to the human population and in assisting skin wound healing, each strain working differently and more effectively in different healing phases. Thus, a combined formula containing different probiotics to modulate various healing phases is desirable.

Evaluation of the effects of a Chinese herb in nonoperative bone fractures in Taiwan: a retrospective multi-central database cohort study

IntroductionBone fracture is a critical issue worldwide, affecting daily activities and increasing living expenses. The effect of Chinese herbs on bone union has been evaluated in recent years. However, its clinical efficacy in the unionisation of bone fractures is not completely elucidated. Zheng-Gu-Zi-Jin-Dang (ZGZJD) is a famous formula in Chinese medicine traumatology that has been widely used in patients with fractures in previous studies. MethodsWe used the Chang Gung Research Database and retrospectively reviewed patients at Chang Gung Memorial Hospital who suffered from bone fractures to evaluate the efficacy of ZGZJD intervention on bone union within 3 months after bone fractures and we used the frequency matching method in a 1:5 ratio for further analysis. ResultsBetween 2004 and 2016, 291851 fractures were diagnosed at Chang Gung Memorial Hospital. A total of 544 patients received ZGZJD, and 2720 patients were match as control which do not use the herbs. However, we adjusted the comorbidities affecting the bone union, sex, age and different body extremities and there were no better healing rate in ZGZJD patient. ConclusionsAlthough ZGZJD is a common formula used in bone fractures, there is no direct clinical evidence that it enhances bone union. However, according to ingredients analysis in ZGZJD, this famous Chinese traumatology medicine may be useful during the inflammatory phase of bone healing.

Clinical outcomes of using operating microscope for alveolar ridge preservation: A randomized controlled trial.

The use of the operating microscope (OM) for extraction and alveolar ridge augmentation (ARP) is increasing due to enhanced magnification and illumination. The primary objective was to compare the wound healing and crestal bone quality after the use of OM and dental loupes (DL) for ARP. Forty non-molar teeth with periapical lesions in need of extraction and ARP from 33 patients were randomly assigned to 2 groups: DL (control) or OM (test). All procedures were performed by 1 surgeon and assessments done by masked examiners. ARP was performed with an allograft and a resorbable collagen membrane. The presence of granulomatous tissue remnants after debridement was recorded. Cone-beam computed tomography (CBCT) and ultrasound (US) scans were taken during the healing phase up to 16-week visits. Bone cores were retrieved from implant osteotomies for histologic analysis. Patient-reported outcome measurements (PROMs) were assessed. All patients completed all study visits except 1 who dropped out before the last visit. After socket debridement, the test group exhibited significantly fewer sites with tissue remnants (p=0.01) and a better healing score at 2-week (p=0.04) and 4-week (p=0.01) time points. There were no significant differences in 12-week crestal bone healing by histology (p=0.1), US (p=0.85), and CBCT healing (p=0.64) at 12weeks, as well as PROMs (p>0.1). Within the limitation of the study, the use of OM for ARP resulted in significantly fewer tissue remnants and favorable early visual wound healing. CBCT and US-derived-crestal bone quality did not show a difference between the 2 groups. Alveolar ridge preservation (ARP) by placing bone particulates in the extraction socket, covered by a wound dressing material, is commonly applied immediately after tooth extraction to reduce jawbone shrinkage in preparation for implant placement later. The jawbone healing varies, depending largely on the ability to remove the etiology, socket features, extent of surgical trauma, and wound stability. Healed jawbone with good quality is favorable for easiness of implant placement and could be related to maintenance of long-term implant health. The surgical microscope with high magnification (up to ∼25×) and co-axial illumination is ideal for assistance in the removal of granulomatous tissue that is believed to interfere with healing, performance of minimally invasive extraction, and stabilization of the wound with meticulous tissue management and fine sutures. This study compared the use of the surgical microscope to dental loupes for ARP in a randomized controlled design. The microscope-assisted ARP is associated with a significantly higher chance of removing granulomatous tissue, favorable early healing, and similar crestal bone quality. Removal of granulomatous tissue is significant for immediate implant placement. This study serves as a model for testing the benefits of the surgical microscope for encouraging early healing in more challenging intraoral surgical procedures.

Effect of Hyperbaric Oxygen Therapy and Adipocyte Stem Cell on the Viability of Degloving Injury: A Murine Model.

Degloving soft tissue injuries (DSTIs) involve skin and tissue detachment from muscle or fascia. Surgical treatments exist, but they cannot prevent necrosis. Our aim was to investigate the effects of hyperbaric oxygen therapy (HOT) and adipocyte stem cell (ASC) treatment on tissue viability in degloving injuries in a murine model. 32 animals were submitted to a degloving flap surgery in the dorsal region and were allocated in four groups (n=8/group): Control: suture only; HOT: 2-hour daily therapy in 100% oxygen at 2.0 ATA for 7 days; ASC: injected with 1x106 stem cells; ASC+HOT: stem cells injection plus HOT therapy. We performed macroscopic measurements, blood flow, histology, and expression of inflammation genes. After 7days, HOT, ASC, and ASC+HOT groups had significantly more viable tissue compared to Control (97%, 90%, 81% vs. 6%). Viable area ratios were higher in HOT and ASC than Control. Blood flow in the injury's distal region was higher in HOT, ASC, and ASC+HOT compared to Control. Vascular density was higher in HOT and ASC+HOT than Control. Inflammatory cells decreased by 40% in HOT, 50% in ASC+HOT, and 75% in ASC. Gene Cd68 expression was lower in HOT than Control. Il10 expression was lower in HOT but higher in ASC and ASC+HOT than Control. This study suggests that the HOT can benefit the degloving injury flap model in the early phase of wound healing, and the association of ASC with HOT could benefit the wound healing in a later phase. This journal requires that authors assign a level of evidence to each submission to which evidence-based medicine rankings are applicable. This excludes review articles, book reviews, and manuscripts that concern basic science, animal studies, cadaver studies, and experimental studies. 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 .

The effect of photobiomodulation therapy on implant stability: A systematic review and meta-analysis.

This study was designed to determine the effect of photobiomodulation therapy on dental implant stability. A complete systematic search was performed in PUBMED/MEDLINE, COCHRANE library databases, EMBASE, SCOPUS, and Google Scholar databases on articles published until June 2024. All the RCTs and CCTs reported the solo impact of photobiomodulation on dental implant stability in humans were included. The means and standard deviation for implant stability and sample size were extracted for the meta-analysis. The statistical analysis was conducted using Stata 17 software, and random effect models were applied to assess the source of heterogeneity. The I2 statistic was used to estimate the significance of any discrepancies in the therapy result. After a full-text inspection, 17 articles were qualified for systematic review, and 14 were included in the meta-analysis. Statically significant differences in implant stability were observed between the laser and the control groups on weeks 2 in ISQ reporting groups (p = 0.01, CI 95%) and weeks 4 and 8 in PTV reporting groups (p < 0.001, CI 95%). Despite limitations, the study suggests that PBM therapy benefits patients with dental implants at different periods, particularly during the early phases of healing.

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions.

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

Duramater Healing Following Decompression And Posterior Stabilization Using Platelet Rich Plasma And Platelet Rich Fibrin: A Systematic Review

Background: Platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade. This systematic review evaluates the efficacy of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in enhancing duramater healing and reducing complications, particularly cerebrospinal fluid (CSF) leaks, following spinal surgeries. Incidental dural tears are a common complication in lumbar spine surgeries, leading to significant postoperative challenges. Methods: The review included randomized controlled trials comparing PRP and PRF with conventional treatments, sourced from databases such as PubMed, ScienceDirect, ProQuest, and Cochrane Library. Results: PRP and PRF are rich in growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β), all of which play crucial roles in wound healing. Conclusion: Both PRP and PRF significantly improve duramater healing, with PRF offering a more sustained release of growth factors, thereby enhancing watertight dura closure and reducing CSF leakage.

Impact of prosthodontic rehabilitation on psychological status and quality of life in maxillectomy patients of coronavirus disease 2019-associated mucormycosis at a tertiary care center: A prospective clinical study

Aims: The study was aimed to evaluate the effect of prosthodontic rehabilitation on psychological status (PS) and quality of life (QoL) in maxillectomy patients of coronavirus disease 2019-associated mucormycosis (CAM). Settings and Design: The study was designed as a prospective and clinical study. Materials and Methods: Twenty-four CAM patients undergoing maxillectomy and subsequent prosthetic rehabilitation were included. The treatment involved surgical, intermediate, and definitive obturator delivery at various phases of healing. PS was assessed using the Hospital Anxiety and Depression Scale (HADS), QOL using the European Organization for Research and Treatment of Cancer QoL Questionnaire-Head and Neck Module (EORTC QLQ-HandN35), and the functioning of obturator was assessed utilising the Obturator Functioning Scale (OFS) at various time points: before maxillectomy (T1), 2 weeks after maxillectomy (T2), 2 weeks upon usage of intermediate obturator (T3), just before delivery of definitive obturator (T4), and 12 weeks after the usage of definitive obturator (T5). Statistical Analysis Used: Data were analyzed using a social science statistical analysis program (Stata 14.0; StataCorp LLC, Texas, USA). The significance level was chosen &lt;0.05. Shapiro–Wilk test was used to assess the normality of quantitative data. Student’s t-test was employed (α =0.05) to evaluate if the patient’s PS, QOL, and obturator function had changed over time. The Spearman correlation coefficient (α =0.05) was utilized to evaluate the correlation coefficient between PS, QOL, and obturator function seen at T3 and T5. Results: Out of 24 enrolled patients, nine were dropped out. HADS-anxiety score was the highest at T1 (18.6 ± 1.2) and HADS-depression score was the highest at T2 (18.8 ± 1.6). HADS scores decreased significantly (P = 0.001) after prosthetic rehabilitation. EORTC QLQ-HandN35 score was the highest at T2 (105.8 ± 29.5), with statistical significance (P = 0.001) after rehabilitation. OFS was the highest at T3 (51.9 ± 3.9) and lowest at T5 (25.4 ± 2.8). Conclusion: CAM and maxillectomy deliberately affects the PS and QOL. Prosthetic rehabilitation, psychological motivation, and education create greater improvement in PS and QOL. The progress in parameters showed an upward trend with good obturator quality over a period of time.

Delayed Hyperperfusion Syndrome During the Healing Phase After Flow Diverter Treatment of Giant Intracranial Aneurysms.

Delayed Hyperperfusion Syndrome During the Healing Phase After Flow Diverter Treatment of Giant Intracranial Aneurysms.

An Advanced Hydrogel Dressing System with Progressive Delivery and Layer-to-Layer Response for Diabetic Wound Healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of SignificanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

Glucose-activated self-cascade antibacterial and pro-angiogenesis nanozyme-functionalized chitosan-arginine thermosensitive hydrogel for chronic diabetic wounds healing

Affected by persistent hyperglycemia, diabetic neuropathy, and vasculopathy hinder the progression of wound healing by exacerbating susceptibility to recurrent bacterial infection and impairing vascularization. In order to cater to the requirements of diabetic chronic wound healing at various stages, we designed an antibacterial and pro-angiogenic wound dressing with localized glucose-lowering capacity. In this study, we constructed a copper-based metal-organic framework (MOF) nanozyme and loaded with glucose oxidase (GOX) to prepare Cu-MOF/GOX, which was subsequently integrated with CS-Arg (chitosan modified by L-Arginine) and Pluronic (F127) to fabricate multifunctional Cu-MOF/GOX-Gel thermosensitive hydrogel. The GOX generated H2O2 (hydrogen peroxide) and gluconic acid by consuming high blood glucose at the wound site, thus initiating an efficient antibacterial self-cascade catalytic in the initial stages of wound healing. With the further catalysis of in situ generated H2O2, NO (nitric oxide) was gradually released from the hydrogel, facilitating angiogenesis and accumulation of collagen, thereby expediting subsequent phases of wound healing. Overall, the Cu-MOF/GOX-Gel exhibits a comprehensive ability to locally regulate blood glucose levels, while also synergistically promoting antibacterial activity and angiogenesis, that effectively chronic diabetic wounds healing.