Connective tissue graft versus xenogeneic collagen matrix for soft tissue augmentation at implant sites: a randomized-controlled clinical trial.

OBJECTIVES: The purpose of this randomized clinical trial (RCT) is to compare xenogeneic collagen matrix (XCM) versus subepithelial connective tissue graft (SCTG) to increase soft tissue thickness at implant site. MATERIALS AND METHODS: The study was a randomized, parallel-group controlled investigation. Thirty patients underwent buccal soft tissue thickness augmentation at the stage of implant placement by two different methods: SCTG (control group) and XCM (test group). Primary outcome was the amount of buccal soft tissue thickness gain, 3 months after the intervention. Secondary outcomes were the operation time, the amount of keratinized mucosa (KM), pain syndrome (PS), and patients' quality of life (QL). Histologic evaluation was also performed. RESULTS: The amount of soft tissue thickness gain was 1.55±0.11 mm in SCTG group, and 1.18±0.11mm in XCM group. The difference between the SCTG and XCM was -0.366 (-0.66 to -0.07; p=0.016). Operation time with XCM was 8.4 (3.737 to 13.06) min shorter than that with the SCTG (p=0.001). KT, PS, and QL for both groups were not statistically significantly different at any time point (p>0.05). At histological examination, the general picture in both groups was similar. No significant differences between the studied groups in most indices, except for the average and maximum formation thickness, cellularity of the basal, mitotic activity and also maximum length of rete ridges. CONCLUSION: Within limitations, this study demonstrates that the use of SCTG provides a statistically significant superior soft tissue thickness gain than XCM for soft tissue augmentation procedures around implants. CLINICAL RELEVANCE: XCM can be used as the method of choice for increasing the thickness of soft tissues.

A Collagen Basketweave from the Giant Squid Mantle as a Robust Scaffold for Tissue Engineering.

The growing applications of tissue engineering technologies warrant the search and development of biocompatible materials with an appropriate strength and elastic moduli. Here, we have extensively studied a collagenous membrane (GSCM) separated from the mantle of the Giant squid Dosidicus Gigas in order to test its potential applicability in regenerative medicine. To establish the composition and structure of the studied material, we analyzed the GSCM by a variety of techniques, including amino acid analysis, SDS-PAGE, and FTIR. It has been shown that collagen is a main component of the GSCM. The morphology study by different microscopic techniques from nano- to microscale revealed a peculiar packing of collagen fibers forming laminae oriented at 60-90 degrees in respect to each other, which, in turn, formed layers with the thickness of several microns (a basketweave motif). The macro- and micromechanical studies showed high values of the Young's modulus and tensile strength. No significant cytotoxicity of the studied material was found by the cytotoxicity assay. Thus, the GSCM consists of a reinforced collagen network, has high mechanical characteristics, and is non-toxic, which makes it a good candidate for the creation of a scaffold material for tissue engineering.

A Case Report of Calyceal Diverticulum: Differential Diagnosis for Organ-Preserving Operations.

Calyceal diverticula and epidermal cysts are extremely rare kidney lesions with unknown etiology and pathogenesis. They have non-specific clinical and radiological picture. Despite the benign nature, sometimes these disorders mimic malignant tumors leading to unjustified nephrectomy. We present a clinical and morphological observation of a multicystic lesion in a 76-year-old patient's right kidney filled with keratinized masses and imitating a malignant solid tumor. The detailed gross, histological and immunohistochemical (desmin, cytokeratin 7, uroplakin and p63) analyses of the kidney tissue excluded the malignant nature of the lesion. The final differential diagnosis was between an epidermal cyst and calyceal diverticulum with pronounced squamous cell metaplasia of urothelium. The upper pole localization of the lesion, its connection with the pelvicalyceal system through the unobstructed isthmus, the presence of urothelial lining and smooth muscle cells in its wall let us diagnose a calyceal diverticulum type I. Knowledge of the key clinical and morphological features of epidermal cysts and diverticula of the pelvicalyceal system will help the practicing physicians suspect the benign nature of such lesions and perform organ-preserving operations.

Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis.

Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, disk-shaped IDDS prototype combining polylactic acid (PLA) and PF, PLA@PF, with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the PLA@PF implants on PIF were examined in the rabbit ear skin pocket model on postoperative days (POD) 30 and 60. Matching blank PLA implants (PLA0) and PLA0 with an equivalent single-dose PF injection performed on POD0 (PLA0+injPF) served as control. On POD30, the intergroup differences were observed in α-SMA, iNOS and arginase-1 expressions in PLA@PF and PLA0+injPF groups vs. PLA0. On POD60, PIF was significantly reduced in PLA@PF group. The peri-implant tissue thickness decreased (532 ± 98 µm vs. >1100 µm in control groups) approaching the intact derma thickness value (302 ± 15 µm). In PLA@PF group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS.

Modeling of Old Scars: Histopathological, Biochemical and Thermal Analysis of the Scar Tissue Maturation.

Mature hypertrophic scars (HSs) remain a challenging clinical problem, particularly due to the absence of biologically relevant experimental models as a standard rabbit ear HS model only reflects an early stage of scarring. The current study aims to adapt this animal model for simulation of mature HS by validating the time of the scar stabilization using qualitative and quantitative criteria. The full-thickness skin and perichondrium excision wounds were created on the ventral side of the rabbit ears. The tissue samples were studied on post-operation days (PODs) 30, 60, 90 and 120. The histopathological examination and morphometry were applied in parallel with biochemical analysis of protein and glycosaminoglycans (GAGs) content and amino acid composition. The supramolecular organization of collagen was explored by differential scanning calorimetry. Four stages of the rabbit ear HS maturation were delineated and attributed with the histolomorphometrical and physicochemical parameters of the tissue. The experimental scars formed in 30 days but stabilized structurally and biochemically only on POD 90-120. This evidence-based model can be used for the studies and testing of new treatments of the mature HSs.

Amianthoid transformation of costal cartilage matrix in children with pectus excavatum and pectus carinatum.

BACKGROUND: It is unclear if amianthoid transformation (AT) of costal cartilage extracellular matrix (ECM) has an impact on the development of pectus excavatum (PE) and pectus carinatum (PC). METHODS: AT foci were examined in intrasurgical biopsy specimens of costal cartilages of children (8-17 years old) with PE (n = 12) and PC (n = 12) and in age-matching autopsy control samples (n = 10) using histological and immunohistochemical staining, atomic force and nonlinear optical microscopy, transmission and scanning electron microscopy, morphometry and statistics. RESULTS: AT areas were identified in the costal cartilage ECM in children with normal chest, PE and PC. Each type of the AT areas ("canonical", "intertwined", "fine-fibred" and "intralacunary") had a unique morphological pattern of thickness and alignment of amianthoid fibers (AFs). AFs were formed via lateral aggregation of collagen type II fibrils in the intact ECM. Foci of the AT were observed significantly more frequently in the PE and PC groups. The AT areas had unique quantitative features in each study group. CONCLUSION: AT is a structurally diverse form of ECM alteration present in healthy and pathological costal cartilage. PE and PC are associated with specific AT disorders.

Evaluation of Supercritical CO2-Assisted Protocols in a Model of Ovine Aortic Root Decellularization.

One of the leading trends in the modern tissue engineering is the development of new effective methods of decellularization aimed at the removal of cellular components from a donor tissue, reducing its immunogenicity and the risk of rejection. Supercritical CO2 (scCO2)-assisted processing has been proposed to improve the outcome of decellularization, reduce contamination and time costs. The resulting products can serve as personalized tools for tissue-engineering therapy of various somatic pathologies. However, the decellularization of heterogeneous 3D structures, such as the aortic root, requires optimization of the parameters, including preconditioning medium composition, the type of co-solvent, values of pressure and temperature inside the scCO2 reactor, etc. In our work, using an ovine aortic root model, we performed a comparative analysis of the effectiveness of decellularization approaches based on various combinations of these parameters. The protocols were based on the combinations of treatments in alkaline, ethanol or detergent solutions with scCO2-assisted processing at different modes. Histological analysis demonstrated favorable effects of the preconditioning in a detergent solution. Following processing in scCO2 medium provided a high decellularization degree, reduced cytotoxicity, and increased ultimate tensile strength and Young's modulus of the aortic valve leaflets, while the integrity of the extracellular matrix was preserved.

Multiparametric Optical Bioimaging Reveals the Fate of Epoxy Crosslinked Biomeshes in the Mouse Subcutaneous Implantation Model.

Biomeshes based on decellularized bovine pericardium (DBP) are widely used in reconstructive surgery due to their wide availability and the attractive biomechanical properties. However, their efficacy in clinical applications is often affected by the uncontrolled immunogenicity and proteolytic degradation. To address this issue, we present here in vivo multiparametric imaging analysis of epoxy crosslinked DBPs to reveal their fate after implantation. We first analyzed the structure of the crosslinked DBP using scanning electron microscopy and evaluated proteolytic stability and cytotoxicity. Next, using combination of fluorescence and hypoxia imaging, X-ray computed microtomography and histology techniques we studied the fate of DBPs after subcutaneous implantation in animals. Our approach revealed high resistance to biodegradation, gradual remodeling of a surrounding tissue forming the connective tissue capsule and calcification of crosslinked DBPs. These changes were concomitant to the development of hypoxia in the samples within 3 weeks after implantation and subsequent induction of angiogenesis and vascularization. Collectively, presented approach provides new insights on the transplantation of the epoxy crosslinked biomeshes, the risks associated with its applications in soft-tissue reconstruction and can be transferred to studies of other types of implants.

Transurethral resection of a large bladder hemangioma of mixed histological composition: a case report.

Hemangioma is a rare benign vascular tumor of the bladder, which occurs mainly in children. It has no specific clinical symptoms but can result in severe and fatal complications as well as relapse. In the current clinical observation, a 35-year-old patient had a large solid tumor of the bladder spreading into the muscular layer. In histological and immunohistochemical analyses, verified hemangioma consisted of capillary, cavernous and arterio-venous components. The patient underwent transurethral resection of the bladder using computer chromoendoscopy. It is the first to the best of our knowledge complete transurethral removal of 3 cm in diameter bladder hemangioma.