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1.
Biomed Microdevices ; 26(3): 29, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888669

ABSTRACT

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery.


Subject(s)
Alginates , Bioprinting , Mesenchymal Stem Cells , Neovascularization, Physiologic , Printing, Three-Dimensional , Tissue Scaffolds , Mesenchymal Stem Cells/cytology , Animals , Tissue Scaffolds/chemistry , Alginates/chemistry , Rats , Gelatin/chemistry , Mesenchymal Stem Cell Transplantation , Cell- and Tissue-Based Therapy , Subcutaneous Tissue , Rats, Sprague-Dawley , Hydrogels/chemistry
3.
ACS Biomater Sci Eng ; 10(6): 3806-3812, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38709857

ABSTRACT

In this work, for the first time, we demonstrate light control of a therapeutic protein's release from a depot in the subcutaneous layer of the skin. The subcutaneous layer is a standard location for therapeutic protein depots due to its large size and ease of access, but prior attempts to utilize this space failed because insufficient light can reach this deeper layer. An analysis of existing biophysical literature suggested that an increase of photoactivation wavelength from 365 to 500 nm could allow an increase of depot irradiation in the subcutaneous by >100-fold. We therefore used a green light-activated thio-coumarin-based material and demonstrated robust release of a therapeutic, insulin, in response to skin illumination with an LED light source. We further demonstrated that this release is ultrafast, as fast or faster than any commercially used insulin, while maintaining the native insulin sequence. This release of insulin was then accompanied by a robust reduction in blood glucose, demonstrating the retention of bioactivity despite the synthetic processing required to generate the material. In addition, we observed that the material exhibits slow basal release of insulin, even in the absence of light, potentially through biochemical or photochemical unmasking of insulin. Thus, these materials can act much like the healthy pancreas does: releasing insulin at a slow basal rate and then, upon skin irradiation, releasing an ultrafast bolus of native insulin to reduce postprandial blood glucose excursions.


Subject(s)
Insulin , Light , Animals , Blood Glucose/metabolism , Blood Glucose/drug effects , Humans , Skin/metabolism , Skin/radiation effects , Skin/drug effects , Coumarins/chemistry , Subcutaneous Tissue/drug effects , Subcutaneous Tissue/metabolism , Male , Green Light
4.
Sci Adv ; 10(20): eadk6178, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38748794

ABSTRACT

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.


Subject(s)
Allografts , Biomarkers , Graft Rejection , Animals , Graft Rejection/immunology , Mice , Skin Transplantation/adverse effects , Heart Transplantation/adverse effects , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Subcutaneous Tissue/pathology , Mice, Inbred C57BL , Mice, Knockout , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
5.
Ital J Dermatol Venerol ; 159(3): 344-348, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38808460

ABSTRACT

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease which not only affect the skin but can also involve the lymph nodes, eyes, and lungs. Subcutaneous sarcoidosis (SCS), is a rare form of sarcoidosis which is generally more prevalent in women in their 40s and 50s, characterized by subcutaneous, flesh-colored nodules, mostly localized on the limbs. A retrospective study to investigate clinical features and response to treatment in patients affected by SCS. METHODS: All patients with systemic and/or cutaneous sarcoidosis visited in our clinic hospital between 2012 and 2022. Out of this group, clinical features, and management of SCS patients were analyzed. RESULTS: Out of 102 patients with specific lesions of cutaneous sarcoidosis, with or without systemic involvement, 13 (13%) were diagnosed with SCS. CONCLUSIONS: Our study confirms that systemic involvement in SCS is the prevalent finding as expected. Moreover, SCS patients have a relatively good prognosis, and systemic treatment does not differ from first-line therapies for cutaneous sarcoidosis.


Subject(s)
Sarcoidosis , Skin Diseases , Humans , Female , Retrospective Studies , Middle Aged , Male , Skin Diseases/etiology , Adult , Aged , Subcutaneous Tissue/pathology
6.
Am Surg ; 90(6): 1514-1520, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38557257

ABSTRACT

INTRODUCTION: The aim of this study is to assess the outcomes of parathyroid gland reimplantation with PR-FaST technique in patients undergoing thyroid surgery, focusing on graft functionality over a 5-year follow-up period. MATERIALS AND METHODS: We analyzed data from 131 patients who underwent parathyroid reimplantation using the PR-FaST technique during thyroid surgery due to inadvertent parathyroid removal or evident vascular damage. Postoperative evaluations included serum calcium (Ca), magnesium (Mg), and phosphorus (P) analyses on the 1st and 2nd postoperative days, at 10 days, and at 1, 3, 6 months, 1 year, and 5 years of follow-up. Additionally, the mean values of serum intact parathyroid hormone (iPTH) concentration were measured from blood samples collected from both the reimplanted arm (iPTH RA) and non-reimplanted arm (iPTH NRA) within the same period. RESULTS: Among 131 patients, at 10 days post-surgery, only 46 patients (35.1%) out of 131 exhibited graft viability (iPTH ratio >1.5). This percentage increased to 72.8% (94 patients) after 1 month and further to 87.8% (108 patients) after 3 months post-surgery. At 1 year, 84.7% of patients showed good graft functionality. After 5 years, the percentage remained stable, with graft viability observed in 81.3% of patients. Only 91 of the initial 131 patients completed follow-up up to 5 years, with a dropout rate of 30.5 %. CONCLUSIONS: Parathyroid reimplantation using the PR-FaST technique is a viable option for patients undergoing thyroidectomy and has been shown to be a reproducible and effective technique in most patients, with sustained graft functionality and parathyroid hormone production over a 5-year follow-up period.


Subject(s)
Forearm , Graft Survival , Parathyroid Glands , Thyroidectomy , Humans , Parathyroid Glands/transplantation , Thyroidectomy/methods , Thyroidectomy/adverse effects , Male , Female , Follow-Up Studies , Middle Aged , Adult , Forearm/surgery , Replantation/methods , Subcutaneous Tissue , Aged , Parathyroid Hormone/blood , Retrospective Studies , Treatment Outcome , Time Factors
7.
Clin Nucl Med ; 49(6): 587-588, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38557426

ABSTRACT

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.


Subject(s)
Adrenal Gland Neoplasms , Gallium Isotopes , Gallium Radioisotopes , Lutetium , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Skin Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/secondary , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology , Heterocyclic Compounds, 1-Ring/therapeutic use , Edetic Acid/analogs & derivatives , Disease Progression , Radioisotopes/therapeutic use , Dipeptides/therapeutic use , Aged , Oligopeptides , Subcutaneous Tissue/diagnostic imaging , Subcutaneous Tissue/pathology , Precision Medicine
8.
Lymphat Res Biol ; 22(2): 147-152, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38630993

ABSTRACT

Background: Recently, the usefulness of lymphatic ultrasound has been reported. It is beneficial not only to identify lymphatic vessels but also to evaluate lymphatic degeneration and diagnose lymphedema. We previously proposed D-CUPS (Doppler, Cross, Uncollapsible, Parallel, and Superficial fascia) to identify the lymphatic vessels on ultrasound. The purpose of this study was to clarify the sensitivity of each index of D-CUPS. Methods: We performed a retrospective study of 27 patients (44 limbs, 98 sites) with lower extremity lymphedema, who underwent lymphaticovenous anastomosis (LVA). We performed a lymphatic ultrasound the day before surgery. We used a linear probe commonly used for venous ultrasound (Noblus EUP-L65; Hitachi Medical Corp., Tokyo, Japan). We applied the D-CUPS index to identify the lymphatic vessels on ultrasound. We checked whether lymphatic vessels consistent with preoperative lymphatic ultrasound findings were observed during the LVA. We also calculated the sensitivity of each D-CUPS index. Results: All the 27 patients were women, with a mean age of 59.7 years. Totally, 98 incisions were made (59 incisions on the thigh and 39 incisions on the lower leg). During LVA, lymphatic vessels consistent with the preoperative lymphatic ultrasound findings were observed at all the sites. The sensitivities of each indicator of D-CUPS were 100.0%, 100.0%, 68.4%, 19.4%, and 100.0%, respectively. Conclusion: The sensitivity was 100.0% in D, C, and S. Although each index separately was not perfect, by combining them appropriately, we were able to identify lymphatic vessels with certainty.


Subject(s)
Lymphatic Vessels , Lymphedema , Humans , Female , Middle Aged , Male , Retrospective Studies , Subcutaneous Tissue , Ultrasonography , Lymphedema/surgery , Lymphography , Lymphatic Vessels/diagnostic imaging , Indocyanine Green
9.
Eur J Histochem ; 68(2)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38619113

ABSTRACT

Knowledge of the structure of the face is of fundamental importance. In fact, the face is treated in many areas of medicine, from dermatology, to maxillofacial surgery, to otorhinolaryngology, to ophthalmology, etc. and anti-aging aesthetic treatments, and those for the resolution of blemishes are on the increase. For ethical reasons it is not possible to take biopsy samples for facial analysis in the aesthetic field. The main aim of this study was to demonstrate that a high-resolution bimodal ultrasound examination, combined with elastosonography, could be a valid tool for pre-treatment morphological evaluation. To achieve this goal, skin samples were taken from the forehead, zygomatic area, nasolabial fold, upper and lower lip from cadavers to histologically characterize their structure. Subsequently, these same areas were evaluated in vivo using conventional B-mode ultrasound with a 24 MHz high-frequency probe, and elastosonography. The data obtained with the different techniques were compared, in order to state that modern ultrasound techniques can provide similar histological information. The analysis showed that the superficial hypodermis presented a different shape and structure in the different areas, with the exception of the areas of the upper and lower lip, which appeared similar. With aging, the forehead and zygomatic area showed a volumetric increase in the superficial hypodermic layer, while the lip showed non-structural changes. The morphology of the nasolabial fold remained unchanged. When it is not possible to perform histological investigations on the face, to understand its characteristics and dynamics, ultrasound with a 24 MHz probe would seem to be the most suitable method, while elastosonography could be a valid method for evaluating the stiffness of the structural components.


Subject(s)
Lip , Subcutaneous Tissue , Ultrasonography
10.
Pharm Res ; 41(4): 751-763, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38443633

ABSTRACT

PURPOSE: To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects. METHODS: A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min. RESULTS: Across all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0-1.5 out of 6). CONCLUSION: SC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min.


Subject(s)
Pain , Subcutaneous Tissue , Humans , Injections, Subcutaneous , Cross-Over Studies , Pain/drug therapy
11.
Ann Biomed Eng ; 52(6): 1638-1652, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38472602

ABSTRACT

Subcutaneous tissue mechanics are important for drug delivery. Yet, even though this material is poroelastic, its mechanical characterization has focused on its hyperelastic response. Moreover, advancement in subcutaneous drug delivery requires effective tissue mimics such as hydrogels for which similar gaps of poroelastic data exist. Porcine subcutaneous samples and gelatin hydrogels were tested under confined compression at physiological conditions and strain rates of 0.01%/s in 5% strain steps with 2600 s of stress relaxation between loading steps. Force-time data were used in an inverse finite element approach to obtain material parameters. Tissues and gels were modeled as porous neo-Hookean materials with properties specified via shear modulus, effective solid volume fraction, initial hydraulic permeability, permeability exponent, and normalized viscous relaxation moduli. The constitutive model was implemented into an isogeometric analysis (IGA) framework to study subcutaneous injection. Subcutaneous tissue exhibited an initial spike in stress due to compression of the solid and fluid pressure buildup, with rapid relaxation explained by fluid drainage, and longer time-scale relaxation explained by viscous dissipation. The inferred parameters aligned with the ranges reported in the literature. Hydraulic permeability, the most important parameter for drug delivery, was in the range k 0 ∈ [ 0.142 , 0.203 ] mm 4 /(N s). With these parameters, IGA simulations showed peak stresses due to a 1-mL injection to reach 48.8 kPa at the site of injection, decaying after drug volume disperses into the tissue. The poro-hyper-viscoelastic neo-Hookean model captures the confined compression response of subcutaneous tissue and gelatin hydrogels. IGA implementation enables predictive simulations of drug delivery.


Subject(s)
Hydrogels , Models, Biological , Subcutaneous Tissue , Animals , Swine , Hydrogels/chemistry , Porosity , Gelatin/chemistry , Elasticity , Compressive Strength , Stress, Mechanical , Finite Element Analysis
12.
Clin Exp Med ; 24(1): 51, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38441683

ABSTRACT

Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is challenging due to the absence of marked lymphadenopathy, the highly heterogeneous clinical presentation, and the rarity of the condition. Clinical presentation is characterized by variable combinations of nonspecific signs and symptoms (such as fever and weight loss), organ-specific focal manifestations due to altered perfusion, and hemophagocytic syndrome. The rarity of this entity and the paucity of neoplastic cells in biopsy samples hamper the study of recurrent molecular abnormalities. The purpose of this study was to explore the feasibility of a different approach to recover a sufficient amount of DNA of acceptable quality to perform next-generation sequencing studies. Here, we report the findings of whole-exome next-generation sequencing performed on a fresh-frozen cutaneous sample of IVLBCL, paired with the patient saliva used as germline DNA. To increase the cancer cell fraction, only the subcutaneous tissue was selected. With this approach, we obtained high-quality DNA and were able to identify oncogenic mutations specific for this entity and recapitulating its post-germinal center origin, even if the tumor fraction was low. Molecular studies performed on fresh-frozen cutaneous sample are feasible in IVLBCL, especially when analysis is restricted to the subcutaneous tissue. Wide adoption of this reproducible and cost-effective approach may foster further studies, which may be of help in supporting diagnosis, providing pathogenetic insights, and guiding treatment decisions.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Exome Sequencing , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Subcutaneous Tissue , DNA
13.
Soft Matter ; 20(21): 4197-4207, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38477130

ABSTRACT

Subcutaneous tissue mechanical response is governed by the geometry and mechanical properties at the microscale and drives physiological and clinical processes such as drug delivery. Even though adipocyte packing is known to change with age, disease, and from one individual to another, the link between the geometry of the packing and the overall mechanical response of adipose tissue remains poorly understood. Here we create 1200 periodic representative volume elements (RVEs) that sample the possible space of Laguerre packings describing adipose tissue. RVE mechanics are modeled under tri-axial loading. Equilibrium configuration of RVEs is solved by minimizing an energetic potential that includes volume change contributions from adipocyte expansion, and area change contributions from collagen foam stretching. The resulting mechanical response across all RVE samples is interpolated with the aid of a Gaussian process (GP), revealing how the microscale geometry dictates the overall RVE mechanics. For example, increase in adipocyte size and increase in sphericity lead to adipose tissue softening. We showcase the use of the homogenized model in finite element simulations of drug injection by implementing a Blatz-Ko model, informed by the GP, as a custom material in the popular open-source package FEBio. These simulations show how microscale geometry can lead to vastly different injection dynamics even if the constituent parameters are held constant, highlighting the importance of characterizing individual's adipose tissue structure in the development of personalized therapies.


Subject(s)
Adipocytes , Subcutaneous Tissue , Adipocytes/cytology , Models, Biological , Humans , Normal Distribution , Biomechanical Phenomena , Finite Element Analysis
14.
J Burn Care Res ; 45(3): 808-810, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38422368

ABSTRACT

Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol. Cefiderocol concentrations in bone and skin/subcutaneous tissue were 13.9 and 35.9 mcg/g, respectively. The patient recovered from bacteremia and underwent autografting without further complications. Cefiderocol at approved dosing of 2 g IV (3-hour infusion) every 8 hours resulted in bone and skin/subcutaneous tissue concentrations adequate to treat extensively drug-resistant Gram-negative bacteria that remain susceptible to cefiderocol.


Subject(s)
Anti-Bacterial Agents , Cefiderocol , Cephalosporins , Pseudomonas Infections , Pseudomonas aeruginosa , Pyoderma Gangrenosum , Humans , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Bone and Bones , Cephalosporins/therapeutic use , Drug Resistance, Multiple, Bacterial , Pseudomonas Infections/drug therapy , Pyoderma Gangrenosum/drug therapy , Skin/microbiology , Skin Transplantation , Subcutaneous Tissue
15.
Tissue Eng Regen Med ; 21(3): 499-511, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38367122

ABSTRACT

BACKGROUND: Dysregulation of skin metabolism is associated with a plethora of diseases such as psoriasis and dermatitis. Until now, reconstructed human skin (RhS) models lack the metabolic potential of native human skin, thereby limiting their relevance to study human healthy and diseased skin. We aimed to determine whether incorporation of an adipocyte-containing hypodermis into RhS improves its metabolic potential and to identify major metabolic pathways up-regulated in adipose-RhS. METHODS: Primary human keratinocytes, fibroblasts and differentiated adipose-derived stromal cells were co-cultured in a collagen/fibrin scaffold to create an adipose-RhS. The model was extensively characterized structurally in two- and three-dimensions, by cytokine secretion and RNA-sequencing for metabolic enzyme expression. RESULTS: Adipose-RhS showed increased secretion of adipokines. Both RhS and adipose-RhS expressed 29 of 35 metabolic genes expressed in ex vivo native human skin. Addition of the adipose layer resulted in up-regulation of 286 genes in the dermal-adipose fraction of which 7 were involved in phase I (CYP19A1, CYP4F22, CYP3A5, ALDH3B2, EPHX3) and phase II (SULT2B1, GPX3) metabolism. Vitamin A, D and carotenoid metabolic pathways were enriched. Additionally, pro-inflammatory (IL-1ß, IL-18, IL-23, IL-33, IFN-α2, TNF-α) and anti-inflammatory cytokine (IL-10, IL-12p70) secretion was reduced in adipose-RhS. CONCLUSIONS: Adipose-RhS mimics healthy native human skin more closely than traditional RhS since it has a less inflamed phenotype and a higher metabolic activity, indicating the contribution of adipocytes to tissue homeostasis. Therefore it is better suited to study onset of skin diseases and the effect of xenobiotics.


Subject(s)
Skin , Subcutaneous Tissue , Humans , Adipose Tissue , Adipocytes , Cytokines
16.
Ann Anat ; 253: 152221, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38309593

ABSTRACT

OBJECTIVE: The superficial cervicofacial musculoaponeurotic system (SMAS) is a complex network formed by mimic muscles and conjunctive tissue of the superficial fascia of the face.This study aimed to introduce new anatomofunctional data on the importance of the trans-SMAS distribution pattern of the skin microperfusion of the face and to underline the role of SMAS in maintaining the homeostasis of the vascular network that crosses it. Considering the fibrous and muscular matrix of the SMAS, using COLIII and MyoH2 antibodies, together with endothelial immunohistochemistry(IHC)intercellular adhesion molecule 2 marker, we determined the correlation of these structures and their interaction. METHODS: This study included 33donors of SMAS tissues, which have been stained withregular hematoxylin and eosin (HE), and three different IHC markers have been used (collagen III, muscular tissue, and blood vessels). The samples were collected from parotid, masseteric, jugal, and zygomatic regions. Magnetic resonance angiography was used to identify the main vascular sources of the midlateral regions of the face of another 47 patients. RESULTS: Significant differences in topographic arrangement, density, and relations of the microsopic vasculature were observed between each of the four regions. Major differences were identified between the role of SMAS in each of these regions, from the parotid capsule to masseteric fascia, transition mobile part, and attaching manners in the zygomatic subunit. CONCLUSIONS: Blood vessel topography must be related with the surrounding conjunctive and muscular tissue, especially regarding facial SMAS. Intrinsic relations between these three components of the SMAS and nervous fibers can provide us important hints on the functionality of the whole system.


Subject(s)
Superficial Musculoaponeurotic System , Humans , Subcutaneous Tissue , Cheek , Fascia , Facial Muscles
17.
J Mater Sci Mater Med ; 35(1): 13, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38353838

ABSTRACT

Intracanal medications are used in endodontic treatment due to their antibacterial activity and ability to induce the periapical repair. Among the intracanal medications, the Calen (CAL; SS. White, Brazil) is a calcium hydroxide-based medication that provides an alkaline pH and releases calcium, exerting an antimicrobial activity. Bio-C Temp (BIO; Angelus, Brazil), a ready-to-use bioceramic intracanal medication, was designed to stimulate the mineralized tissues formation. Here, we investigated the bioactive potential of BIO in comparison to the CAL in the rat subcutaneous. Polyethylene tubes filled with medications, and empty tubes (control group, CG) were implanted in the subcutaneous tissue of rats. After 7, 15, 30 and 60 days, the blood was collected for calcium (Ca+2) and alkaline phosphatase (ALP) measurement, and the capsules around the implants were processed for morphological analyses. The data were submitted to two-way ANOVA and Tukey test (p < 0.05). At 7, 15 and 30 days, the ALP level was grater in BIO and CAL than in CG (p < 0.0001). At 7 and 15 days, greater Ca+2 level was seen in the serum of CAL samples. From 7 to 60 days, an increase in the number of fibroblasts, osteocalcin- and osteopontin-immunolabelled cells was observed in BIO and CAL groups (p < 0.0001). In all periods, BIO and CAL specimens showed von Kossa-positive structures. Moreover, ultrastructural analysis revealed globules of mineralization in the capsules around the BIO and CAL specimens. Thus Bio-C Temp caused an increase in the ALP, osteocalcin and osteopontin, which may have allowed the formation of calcite, suggesting bioactive potential.


Subject(s)
Calcinosis , Osteopontin , Animals , Rats , Osteocalcin , Calcium , Subcutaneous Tissue , Anti-Bacterial Agents
18.
Biomacromolecules ; 25(3): 1439-1447, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38349078

ABSTRACT

Beta cell replacement therapies utilizing the subcutaneous space have inherent advantages to other sites: the potential for increased accessibility, noninvasive monitoring, and graft extraction. Site prevascularization has been developed to enhance islet survivability in the subcutaneous zone while minimizing potential foreign body immune responses. Molecular communication between the host and prevascularized implant site remains ill-defined. Poly(ethylene oxide)s (PEOs) of various hydrated radii (i.e., ∼11-62 Å) were injected into prevascularized subcutaneous sites in C57BL/6 mice, and the clearance and organ biodistribution were characterized. Prevascularization formed a barrier that confined the molecules compared with the unmodified site. Molecular clearance from the prevascularized site was inversely proportional to the molecular weight. The upper limit in molecular size for entering the vasculature to be cleared was determined to be 35 kDa MW PEO. These findings provide insight into the impact of vascularization on molecular retention at the injection site and the effect of molecular size on the mobility of hydrophilic molecules from the prevascularized site to the host. This information is necessary for optimizing the transplantation site for increasing the beta cell graft survival.


Subject(s)
Insulin-Secreting Cells , Islets of Langerhans Transplantation , Mice , Animals , Tissue Distribution , Mice, Inbred C57BL , Subcutaneous Tissue/blood supply , Neovascularization, Physiologic
19.
Burns ; 50(5): 1241-1246, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38378389

ABSTRACT

Negative Pressure Wound Therapy (NPWT) is broadly used in surgical wound management and more recently burn care; however, the tissue pressure changes and best dressing application technique remains unknown. This study was done to help understand the tissue pressure changes beneath negative pressure when varying the delivered pressures, dressing thickness and distribution of dressings. This study was done in 2021 at a quaternary paediatric burns hospital. Utilising a cadaveric porcine model, an intracranial pressure monitor and transducer were used to assess pressure. The transducer was placed on the epidermis or inserted under ultrasound guidance via cannulation to the dermis, subcutaneous or muscular layer. Mepitel™, ACTICOAT™, varying layers of Kerlix™ (10, 20 or 30 layers) and NPWT were then applied either circumferentially or non-circumferentially. Each set of results is indicative of the intracranial pressure probe reading when NPWT was delivered at -40, -60, -80, -100 and -120 mmHg. The median and interquartile pressure recordings were epidermis: -42 (-42.5 - -41), -60.5 (-62.5 - -60), -80.5 (-82 - -80), - 99 (-99 - -98)mmHg (p < 0.001); dermis: 1 (0 - 2), 2 (1 - 3.5), 3 (2 - 5.5), 4 (3 - 7), 5.5 (4 - 7.5)mmHg (p < 0.001) (the increase in pressure was less when circumferential dressings (p < 0.001) or more layers of Kerlix were applied (p < 0.001)); subcutis: 1.5 (-4.5-1), -2.5 (-7.5 - 1.5), -3.5 (-11 - 1.5), -5 (-14 - 1.5) and -6 (-16 - 2)mmHg (p = 006) (the decrease in pressure was less with increased layers of Kerlix (0.047) and muscular: 0 (-0.5 - 0), 0 (-1 - 0.5), 0 (-1 - 1), 0 0 (-1 - 1), 00 (-1.5 - 1)mmHg (p = 0.55). These data suggest negative pressure paradoxically exerts a positive pressure on the dermis. Circumferential and multi-layer dressings reduce this positive pressure. This knowledge has impacted our burn negative pressure wound therapy dressing selection. The limitation of this study is the cadaveric model, a live model is suggested for future studies.


Subject(s)
Bandages , Negative-Pressure Wound Therapy , Animals , Negative-Pressure Wound Therapy/methods , Swine , Burns/therapy , Disease Models, Animal , Intracranial Pressure , Pressure , Epidermis , Wound Healing , Dermis , Subcutaneous Tissue
20.
Eur Rev Med Pharmacol Sci ; 28(1): 357-364, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38235887

ABSTRACT

OBJECTIVE: The aim of this prospective cross-sectional study was to investigate whether cleaning the episiotomy line with rifampicin solution before suturing will reduce infection and wound dehiscence in women who had vaginal delivery with episiotomy. PATIENTS AND METHODS: A prospective cross-sectional study was conducted with a total of 400 primigravida patients. In the study group, irrigation with rifampicin of the subcutaneous tissue of the episiotomy incision was applied, and in the control group, there was no irrigation. Patients were evaluated for infection at the 1st, 3rd week, and 1-month controls. The groups were compared according to episiotomy infection and wound dehiscence rates. RESULTS: The episiotomy infection rate of the whole group was 8.5%, the wound dehiscence rate was 3.75%, and the average time of occurrence of the infection was 5.35±2.21 days. The most common infection findings were local pain and purulent discharge at 4.75%. In the control group, where the infection occurred earlier, the infection and wound dehiscence rates were significantly higher [11.5% vs. 5.5%; 6.0% vs. 1.5% (p<0.05)]. Purulent discharge was the most common finding in the control group, and local pain in the study group, but no significant difference was found between the two groups in terms of findings (p<0.05). When only the patients who developed episiotomy infection were evaluated among themselves, the only significant difference was found in wound dehiscence, which was higher in the control group (p<0.05). CONCLUSIONS: Considering the high rates of episiotomy in our country, subcutaneous irrigation with rifampicin is a good option that can be kept in the foreground due to its low cost and ease of application.


Subject(s)
Episiotomy , Rifampin , Pregnancy , Humans , Female , Episiotomy/adverse effects , Rifampin/therapeutic use , Subcutaneous Tissue , Prospective Studies , Cross-Sectional Studies , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Pain , Perineum
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