Tissue Defects Research Articles

Advancing Fingertip Regeneration: Outcomes from a New Conservative Treatment Protocol.

Background Fingertip injuries with volar pulp tissue defects present a significant challenge in management. This study aimed to evaluate the efficacy of a conservative treatment protocol using artificial dermis and semi-occlusive dressings for these injuries. Methods A single-center, prospective study was conducted on 31 patients with fingertip injuries involving volar pulp defects. The treatment protocol included wound debridement, application of artificial dermis (Pelnac®), and a semi-occlusive dressing (IV3000®). The outcomes were assessed using subjective questionnaires and objective measures, including fingerprint regeneration, sensory function, pain, and cosmetic appearance. Results The mean treatment duration was 45.29 days (SD = 17.53). Complications were minimal, with only one case (3.22%) directly attributable to the treatment. Fingerprint regeneration was considerable (mean score = 2.58, SD = 0.67). The sensory disturbances were minimal, with no significant differences across injury types. Post-treatment pain was low (mean = 0.45, SD = 0.67), and cosmetic satisfaction was high (mean = 4.09, SD = 0.94). The overall patient satisfaction was high (mean = 4.41, SD = 0.67), regardless of injury severity. Conclusions The conservative treatment protocol using artificial dermis and semi-occlusive dressings is a promising strategy for managing fingertip injuries with volar pulp defects. This approach minimizes surgical morbidity and achieves excellent functional and aesthetic outcomes.

Induced pluripotent stem cells: A game-changer in dentistry’s regenerative landscape

In recent years, induced pluripotent stem cells (iPSCs) have emerged as a transformative force in regenerative medicine, offering unprecedented opportunities for advancements in various fields. This review explores the revolutionary impact of iPSCs specifically within the realm of dentistry, where regenerative strategies are increasingly sought to address oral and craniofacial tissue defects. iPSCs, derived from somatic cells through reprogramming, exhibit pluripotency and can differentiate into various cell types, including dental-specific lineages such as odontoblasts, ameloblasts, and osteoblasts. The application of iPSCs in dentistry holds immense promise for tissue repair, regeneration, and disease modelling. This review delves into the key aspects of iPSC-based approaches in dental research, covering topics such as tooth regeneration, periodontal tissue engineering, and craniofacial defect repair. We discuss the challenges and advancements in iPSC technology, emphasizing the potential for personalized regenerative therapies tailored to individual patients.

Digital Light Processing of 19F MRI-Traceable Gelatin-Based Biomaterial Inks towards Bone Tissue Regeneration.

Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which allows for the production of various scaffold microarchitectures in line with the anatomical requirements of the organ to be replaced or tissue defect to be treated. Upon their in vivo utilization, the main bottleneck is to monitor cell colonization along with their degradation (rate). In order to enable non-invasive visualization, labeling with MRI-active components like N-(2,2-difluoroethyl)acrylamide (DFEA) provides a promising approach. Herein, we report on the development of a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink in combination with DFEA, applicable in digital light processing-based additive manufacturing towards bone tissue regeneration. The fabricated hydrogel constructs show excellent shape fidelity in line with the printing resolution, as DFEA acts as a small molecular crosslinker in the system. The constructs exhibit high stiffness (E = 36.9 ± 4.1 kPa, evaluated via oscillatory rheology), suitable to serve bone regeneration and excellent MRI visualization capacity. Moreover, in combination with adipose tissue-derived stem cells (ASCs), the 3D-printed constructs show biocompatibility, and upon 4 weeks of culture, the ASCs express the osteogenic differentiation marker Ca2+.

Microbiological challenges in the treatment of war injuries

The treatment of war injuries represents a continuing and recurrent challenge in modern reconstructive surgery. Previously, tumor resections and sepsis-related resections were mainly responsible for lengthy bone defects in Germany. In recent years another picture has increasingly emerged, particularly caused by the medical support of Ukraine. Aspects of military surgery are also becoming more important in civil hospitals, especially in the treatment of gunshot and explosion injuries. In Germany, war injuries are currently secondarily treated, as the distribution of patients is carried out according to the cloverleaf principle, weeks or months after the occurrence of the primary injury. In addition to complex bone and soft tissue defects of the extremities following such injuries, which often affect neural and vascular structures, reconstruction is often complicated by an increasing spectrum of multidrug-resistant pathogens. The definition of microbiological terms, such as contamination, colonization, critical colonization, local and systemic infections are important in the clinical routine in order to initiate a targeted treatment, especially in treatment with antibiotics. Wound swabs for determination of the spectrum of pathogens and the optimal testing of resistance are important for selecting the appropriate antibiotic agents. The concept of antibiotic stewardship (ABS) is established in many hospitals to improve the quality of antibiotic treatment and to minimize the formation of resistance. The selection of the method of reconstruction depends on the condition of the patient, the overall clinical constellation and the function to be expected after completion of treatment. The treatment of injuries due to violence and terrorism necessitates clear concepts and an interdisciplinary approach, especially with respect to microbiological challenges and increasing resistance situations.

Application of Free Flaps in Reconstruction of Head and Neck Soft Tissue Defects With Bone Exposure.

Reconstruction of head and neck soft tissue defects with bone exposure is both challenging and technically demanding for plastic surgeon. Objectives in head and neck soft tissue defects with bone exposure reconstruction are consistent restoration of functionality while also improving appearance. This study retrospectively analyzed the results of head and neck reconstructions using various types of free flaps over the past 4 years. A retrospective analysis was conducted from June 2019 to June 2023 on 12 patients treated at our hospital for head and neck soft tissue defects with bone exposure due to various causes. These included 4 cases of trauma from car accidents, 1 burn case, and 7 postoperative malignant tumor removals. The defect sizes ranged from 4 × 6 to 15 × 45 cm. Different free flaps were used for repair based on the defect, including 6 anterolateral thigh flaps, 3 forearm flaps, 2 latissimus dorsi flaps, and 1 dorsalis pedis flap. Flaps were designed and harvested to match the defect size and transplanted via anastomosed vessels. All 12 flaps survived successfully. One patient required flap thinning surgery postoperatively. All patients were followed up for over 3 months, showing good color and texture of the transplanted flaps, satisfactory healing, and significant aesthetic improvement. Donor sites showed significant scarring without functional impairment. Free flap repair for head and neck soft tissue defects with bone exposure is feasible and yields good results.

Acute and post-acute soft tissue reconstruction

The precise analysis of the injured structures requiring reconstruction in complex wound defects is aprerequisite for successful restoration. The fundamental reconstructive strategies for soft tissue defects of the extremities including injuries to vessels, nerves and burn wounds in the context of the acute and post-acute trauma phases are presented. The different phases of soft tissue reconstruction are described. Recommendations for action with respect to the reconstruction of the functional structures are described. Two clinical case examples illustrate the approach. The acute reconstruction phase is defined as the period 0-72 h after the traumatic event and includes surgical debridement, primary reconstruction of nerves and vessels using interpositional grafts if necessary and temporary soft tissue reconstruction. Combined thermomechanical trauma requires early debridement combined with internal fixation of open fractures. In the post-acute reconstruction phase, which is generally defined as aperiod of up to 6weeks after the traumatic event, definitive soft tissue reconstruction is performed. In the case of long reinnervation distances, nerve transfer or motor replacement plastic surgery is performed in the post-acute phase. The reconstruction of soft tissue after trauma necessitates a stage-dependent approach. In the acute phase procedures aim at the immediate preservation of the limb. In the post-acute phase, definitive soft tissue reconstruction is performed to enable maximum functional preservation. Combined thermomechanical injuries require early surgical treatment in order to prevent infections.

Clinical applications and cadaveric study of the free descending genicular artery perforator flap without the saphenous vein

SummaryBackgroundThe descending genicular artery (DGA) and medial thigh region have been underused as donor sites for perforator flaps. This study evaluated the anatomical relationship between the perforators of the DGA and the saphenous vein (SV) to review the clinical applications of the free descending genicular artery perforator (DGAP) flap for locoregional reconstruction.MethodsFifteen cadavers were arterially perfused with red latex and dissected. Thirty-one patients with extremity tissue defects were treated with a free DGAP flap, including six patients who received a chimeric flap. The minimum distance between the DGAP and the SV was measured during surgery.ResultsIn all patients, the skin branch of the descending genicular artery was found in the medial femoral condyle plane in front of the SV. The average distance between the descending genicular artery perforator and the SV was 3.71 ± 0.38 cm (range: 2.9–4.3 cm). Thirty flaps survived completely, and one flap developed partial necrosis; however, this flap healed two weeks after skin grafting. The average follow-up time was 11.23 months.ConclusionsWe conclude that the SV can be preserved when harvesting the descending genicular artery perforator flap, causing less damage to the donor site and having no effect on flap survival. The free descending genicular artery perforator flap without the SV is a better therapy for complicated tissue defects.

A case of congenital malformation of the brain in a newborn on the background of hereditary metabolic disorders

A clinical observation of congenital malformation of the brain in a newborn child is presented. Diagnosis and comprehensive treatment of newborns with such pathology is extremely difficult due to the variety of causes that cause irreversible structural defects of brain tissue in violation of its normal pre- or postnatal development. The uniqueness of this case is the postnatal detection of multiple malformations in a newborn child against the background of a complex clarification of the nature of hereditary metabolic disorders. Unfortunately, in this clinical case, the relatively early diagnosis of peroxisomal pathology did not allow a complete clinical diagnosis to be made quickly and specific therapy to be given to the child, which made the prognosis of the disease more difficult. Only a further in-depth examination (consultations of a geneticist, neurologists, MRI of the brain, medical and genetic research) allowed us to clarify the nature of the pathology. Delayed clarification and confirmation of the cause of encephalomyelopathy (peroxisomal disease) is associated with the material and technical capabilities of children's hospitals, although this did not affect the timing of the start and volume of complex symptomatic therapy for the child.

Submental Flap Versus Radial Forearm Free Flap for the Reconstruction of Medium Size Soft Tissue Defect in the Oral Cavity.

The aim of this work is to compare the functional and esthetic outcome of the submental flap and radial forearm free flap for the reconstruction of medium-sized soft tissue defect in the oral cavity. Patients diagnosed with squamous cell carcinoma of the oral cavity and reconstructed with a submental flap or radial forearm free flap between 2015 and 2020 were reviewed and analyzed. Tumor site, complication at the donor site, complication at the recipient site, duration of the hospital stay, local or cervical recurrence, and esthetic results were also analyzed to compare the difference in outcomes between the two groups. Submental flap represents a safe and useful reconstructive recourse for head and neck reconstructive surgeons when it is correctly indicated. Lower rate of complication at the donor site, better esthetic result, and a shorter hospital stay represent the strengths of this flap when it is not necessary to perform compartment surgery. However, more studies are needed with a larger number of patients.

Diffusion‐induced phase separation 3D printed scaffolds for dynamic tissue repair

AbstractMany hydrogen‐bonded cross‐linked hydrogels possess unique properties, but their limited processability hinders their potential applications. By incorporating a hydrogen bond dissociator (HBD) into these hydrogels, we developed injectable 3D printing inks termed diffusion‐induced phase separation (DIPS) 3D printing inks. Upon extrusion into water and subsequent diffusion of HBD, these ink cure rapidly. The DIPS‐printed scaffold retained most of the original hydrogel properties due to the regeneration of hydrogen bonds. Additionally, the reversible nature of hydrogen bonds provides DIPS 3D‐printed scaffolds with exceptional recycling and reprinting capabilities, resulting in a reduction in the waste of valuable raw ink materials or additives. Postprocessing introduces new crosslinking methods that modulate the mechanical properties and degradation characteristics of DIPS scaffolds over a broad range. Based on its suitable mechanical properties and bioactivity, we successfully repaired and functionally reconstructed a complex defect in penile erectile tissue using the DIPS scaffold in a rabbit model. In summary, this approach is relevant for various hydrogen‐bonded cross‐linked hydrogels that offer mild printing conditions and enable the incorporation of bioactive agents. They can be used as scaffolds for dynamic tissue reconstruction, wearable devices, or soft robots.

Use of thigh fascia autograft for repairing a through-and-through soft tissue defect in the alveolar process: a clinical case

Relevance. In most cases, soft tissue defects can be addressed using standard local flap transposition methods. However, large defects and/or those with scar tissue changes, through-and-through defects involving destruction of both vestibular and palatal cortical plates, defects penetrating into the nasal cavity, and similar situations necessitate unconventional solutions utilizing external graft materials.Clinical case description. This clinical case details the use of an autograft from the wide fascia of the thigh (Fascia lata) to repair an atypical defect of the alveolar process in the maxilla, specifically in the area of teeth 1.2 and 1.1. This defect exhibited through penetration between the vestibule of the oral cavity and the oral cavity proper, along with a significant deficiency of local tissues required for defect closure. The results of clinical, instrumental, and CT examinations conducted before and after the surgical intervention are presented.Results. Objective clinical studies conducted three months post-operation showed complete closure of the defect in the alveolar process of the maxilla, with full epithelization in the postoperative intervention area.

Challenge of limb care after violence and war with aspecial focus on imaging procedures

Injury patterns in the area of the extremities following violence and war harbor many special features and require special attention. Destructive and complex defect injuries are often present, which necessitate elaborate and special reconstruction approaches, predominantly as part of astaged and multistaged procedure. In this context, special attention must be paid to the diagnostic options as an essential aspect, as aclear diagnosis means that targeted treatment steps can be planned and implemented. The authors' experience in this field from military operations in Afghanistan, Iraq, the Republic of Mali, Kosovo and Georgia, as well as the core content of the Terror and Disaster Surgical Care (TDSC®) course on this topic, have been contextualized and incorporated. In addition, aspects of interdisciplinary cooperation with radiological and, in particular, nuclear medicine disciplines are taken into account in the daily routine. Extremity injuries in the context of violence and war are accompanied by complex bone and surrounding soft tissue defects due to the high energy impact. The principles of reconstruction familiar from everyday life can only be transferred one-to-one to alimited extent. The treatment pathways are often very long and complex and the questions of infection and tissue vitality must be answered again and again in stages. Interdisciplinary collaboration with the disciplines specialized in imaging procedures, particularly in the field of nuclear medicine, is one of the key building blocks for a successful treatment pathway.

Multifunctional bilayer nanofibrous membrane enhances periodontal regeneration via mesenchymal stem cell recruitment and macrophage polarization

The continuous stimulation of periodontitis leads to a decrease in the number of stem cells within the lesion area and significantly impairing their regenerative capacity. Therefore, it is crucial to promote stem cell homing and regulate the local immune microenvironment to suppress inflammation for the regeneration of periodontitis-related tissue defects. Here, we fabricated a novel multifunctional bilayer nanofibrous membrane using electrospinning technology. The dense poly(caprolactone) (PCL) nanofibers served as the barrier layer to resist epithelial invasion, while the polyvinyl alcohol/chitooligosaccharides (PVA/COS) composite nanofiber membrane loaded with calcium beta-hydroxy-beta-methylbutyrate (HMB-Ca) acted as the functional layer. Material characterization tests revealed that the bilayer nanofibrous membrane presented desirable mechanical strength, stability, and excellent cytocompatibility. In vitro, PCL@PVA/COS/HMB-Ca (P@PCH) can not only directly promote rBMSCs migration and differentiation, but also induce macrophage toward pro-healing (M2) phenotype-polarization with increasing the secretion of anti-inflammatory and pro-healing cytokines, thus providing a favorable osteoimmune environment for stem cells recruitment and osteogenic differentiation. In vivo, the P@PCH membrane effectively recruited host MSCs to the defect area, alleviated inflammatory infiltration, and accelerated bone defects repair. Collectively, our data indicated that the P@PCH nanocomposite membrane might be a promising biomaterial candidate for guided tissue regeneration in periodontal applications.

Selecting Flap Transfer Methods to Repair Helix Soft Tissue Defect Based on the Direction of Long Axis.

The posterior auricular flap has long been favored for repairing skin defects on the ear's surface. However, achieving optimal esthetic outcomes in ear reconstruction requires a flexible approach to flap transfer methods. While bipedicle advancement flaps are commonly used for body wound coverage, they are rarely used in auricular defect repair. To propose a modified flap transfer approach based on the orientation of the auricular defect's long axis and assess the postoperative esthetic outcomes. The authors reported 12 patients treated using 2 distinct flap transfer techniques. Mild to moderate helix soft tissue defects remained after excision of the masses. A direct island flap was created for patients with longitudinal defects to cover the defect. For patients with transverse defects, a combination of bipedicle and island flaps was used for repair. Scar quality and esthetic outcomes were assessed at least 6 months postsurgery using the Scar Cosmesis Assessment and Rating scale. All patients experienced no serious complications and achieved excellent cosmetic results. Patients undergoing combined flap transfer exhibited relatively more favorable esthetic outcomes. The authors propose a novel concept for repairing helix soft tissue defects by designing local flaps based on the direction of the defect's long axis. For repairing helix soft tissue defects with a long axis parallel to the auricular edge, the combined utilization of bipedicle advancement flap and island rotation flap transfer should be consideration more.

Variants in the Kallikrein Gene Family and Hypermobile Ehlers-Danlos Syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common heritable connective tissue disorder that lacks a known genetic etiology. To identify genetic contributions to hEDS, whole exome sequencing was performed on families and a cohort of sporadic hEDS patients. A missense variant in Kallikrein-15 (KLK15 p. Gly226Asp), segregated with disease in two families and genetic burden analyses of 197 sporadic hEDS patients revealed enrichment of variants within the Kallikrein gene family. To validate pathogenicity, the variant identified in familial studies was used to generate knock-in mice. Consistent with our clinical cohort, Klk15 G224D/+ mice displayed structural and functional connective tissue defects within multiple organ systems. These findings support Kallikrein gene variants in the pathogenesis of hEDS and represent an important step towards earlier diagnosis and better clinical outcomes.

The use of peroneus brevis in lower limb reconstruction—What we have learned from 49 cases

IntroductionThere are many suitable techniques for the treatment of soft tissue defects of the lower limb. Older subjects often with multiple comorbidities, presenting with a laterally located and complex defect, can be challenging to treat. This cohort are often unsuited to long procedures or multi-stage reconstruction and so one is faced with a paucity of options. In such instances, we use the peroneus brevis (PB) muscle flap as a single stage procedure. MethodsWe performed a retrospective study evaluating the use of PB flaps in lower limb injury. Subjects were collated using a database and multiple variables were assessed including: patient demographics, comorbidities, defect size, peri-operative timings, time in theatre, use of inotropes / blood transfusion, mean hospital stay, patient morbidity / mortality, flap survival. ResultsDuring 2015–2023, 49 patients underwent lower limb reconstruction using PB muscle flaps. 42 cases involved PB and skin graft alone whilst seven were more complex requiring additional local and free tissue techniques. The most common indication (n = 28) was infection after closed fracture fixation, followed by open trauma (n = 21).Median patient age was 59 (20–93 years), and ASA grade 3. Median defect size was 4 × 7 cm (2–18 cm) and time from admission to definitive closure 4 days (0–21 days) with median time in theatre 120 min (45–520 min). 17 patients required inotropes and 13 had blood transfusion. Median length of hospital stay was 12 days (0–58 days), one patient (aged 90) died. 100 % of flaps survived and median Enneking score was 65. Heterotopic ossification was not identified in the post-operative imaging within the first year. DiscussionOur experience highlights the benefits and risks of using the PB flap and advocates it as a reliable, cost-effective, 1-stage technique for reconstructing small lateral defects in the distal third of the lower limb.

Diverse Fgfr1 signaling pathways and endocytic trafficking regulate mesoderm development.

The fibroblast growth factor (FGF) pathway is a conserved signaling pathway required for embryonic development. Activated FGF receptor 1 (FGFR1) drives multiple intracellular signaling cascade pathways, including ERK/MAPK and PI3K/AKT, collectively termed canonical signaling. However, unlike Fgfr1-null embryos, embryos containing hypomorphic mutations in Fgfr1 lacking the ability to activate canonical downstream signals are still able to develop to birth but exhibit severe defects in all mesodermal-derived tissues. The introduction of an additional signaling mutation further reduces the activity of Fgfr1, leading to earlier lethality, reduced somitogenesis, and more severe changes in transcriptional outputs. Genes involved in migration, ECM interaction, and phosphoinositol signaling were significantly downregulated, proteomic analysis identified changes in interactions with endocytic pathway components, and cells expressing mutant receptors show changes in endocytic trafficking. Together, we identified processes regulating early mesoderm development by mechanisms involving both canonical and noncanonical Fgfr1 pathways, including direct interaction with cell adhesion components and endocytic regulation.

Clinical Performance of Implant-Supported Prostheses in the Rehabilitation of Patients Previously Treated for Medication-Related Osteonecrosis of the Jaws (MRONJ): A Systematic Review.

There is a lack of consensus on managing resultant bone and soft tissue defects or on restoring oral function and aesthetics following medication-related osteonecrosis of the jaws (MRONJ) lesion healing. This clinical challenge presents a dilemma for practitioners. Removable prostheses pose a recurrence risk if poorly fitted and may inadequately restore function or aesthetics in cases of significant bone defect. Dental implant-supported prostheses could enhance function and quality of life, though their risks and indications are not well-defined. This systematic review examines the clinical outcomes and complications associated with implant-supported rehabilitations post-MRONJ surgery. This study was conductedfollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations and it was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO) (CRD42023492539).

Assessment of the Utility of Submental Flap in Reconstructing Soft Tissue Defects after Excision of Small Oral Cancers

Assessment of the Utility of Submental Flap in Reconstructing Soft Tissue Defects after Excision of Small Oral Cancers

Personalized Decisional Algorithms for Soft Tissue Defect Reconstruction after Abdominoperineal Resection for Low-Lying Rectal Cancers.

Abdominoperineal resection (APR)-the standard surgical procedure for low-lying rectal cancer (LRC)-leads to significant perineal defects, posing considerable reconstruction challenges that, in selected cases, necessitate the use of plastic surgery techniques (flaps). To develop valuable decision algorithms for choosing the appropriate surgical plan for the reconstruction of perineal defects. Our study included 245 LRC cases treated using APR. Guided by the few available publications in the field, we have designed several personalized decisional algorithms for managing perineal defects considering the following factors: preoperative radiotherapy, intraoperative position, surgical technique, perineal defect volume, and quality of tissues and perforators. The algorithms have been improved continuously during the entire period of our study based on the immediate and remote outcomes. In 239 patients following APR, the direct closing procedure was performed versus 6 cases in which we used various types of flaps for perineal reconstruction. Perineal incisional hernia occurred in 12 patients (5.02%) with direct perineal wound closure versus in none of those reconstructed using flaps. The reduced rate of postoperative complications suggests the efficiency of the proposed decisional algorithms; however, more extended studies are required to categorize them as evidence-based management guide tools.