Structural Mechanisms in Soft Fibrous Tissues: A Review

Through years of evolution, biological soft fibrous tissues have developed remarkable functional properties, unique hierarchical architectures, and -most notably, an unparalleled and extremely efficient deformation ability. Whereas the structure-function relationship is well-studied in natural hard materials, soft materials are not getting similar attention, despite their high prevalence in nature. These soft materials are usually constructed as fiber-reinforced composites consisting of diverse structural motifs that result in an overall unique mechanical behavior with large deformations. Biomimetics of their mechanical behavior is currently a significant bioengineering challenge. The unique properties of soft fibrous tissues stem from their structural complexity, which, unfortunately, also hinders our ability to generate adequate synthetic analogs, such that autografts remain the “gold standard” materials for soft-tissue repair and replacement. This review seeks to understand the structural and deformation mechanisms of soft collagenous tissues, with a particular emphasis on tendon and ligaments, the annulus fibrosus (AF) in the intervertebral disc (IVD), skin, and blood vessels. We examined and compared different mechanical and structural motifs in these different tissue types, which are subjected to complex and varied mechanical loads, to isolate the mechanisms of their deformation behavior. Herein, we focused on their composite structure from a perspective of the different building blocks, architecture, crimping patterns, fiber orientation, organization and their structure-function relationship. In the second part of the review, we presented engineered soft composite applications that used these structural motifs to mimic the structural and mechanical behavior of soft fibrous tissues. Moreover, we demonstrated new methodologies and materials that use biomimetic principles as a guide. These novel architectural materials have tailor-designed J-shaped large deformations behavior. Structural motifs in soft composites hold valuable insights that could be exploited to generate the next generation of materials. They actually have a two-fold effect: 1) to get a better understanding of the complex structure-function relationship in a simple material system using reverse biomimetics and 2) to develop new and efficient materials. These materials could revolutionize the future tailor-designed soft composite materials together with various soft-tissue repair and replacement applications that will be mechanically biocompatible with the full range of native tissue behaviors.

High Frequency Ultrasonic Wave Propagation in Anisotropic Materials

<p>The influence of highly regular, anisotropic, microstructured materials on high frequency ultrasonic wave propagation was investigated in this work. Microstructure, often only treated as a source of scattering, significantly influences high frequency ultrasonic waves, resulting in unexpected guided wave modes. Tissues, such as skin or muscle, are treated as homogeneous by current medical ultrasound systems, but actually consist of highly anisotropic micron-sized fibres. As these systems increase towards 100 MHz, these fibres will significantly influence propagating waves leading to guided wave modes. The effect of these modes on image quality must be considered. However, before studies can be undertaken on fibrous tissues, wave propagation in more ideal structures must be first understood. After the construction of a suitable high frequency ultrasound experimental system, finite element modelling and experimental characterisation of high frequency (20-200 MHz) ultrasonic waves in ideal, collinear, nanostructured alumina was carried out. These results revealed interesting waveguiding phenomena, and also identified the potential and significant advantages of using a microstructured material as an alternative acoustic matching layer in ultrasonic transducer design. Tailorable acoustic impedances were achieved from 4-17 MRayl, covering the impedance range of 7-12 MRayl most commonly required by transducer matching layers. Attenuation coefficients as low as 3.5 dBmm-1 were measured at 100 MHz, which is excellent when compared with 500 dBmm-1 that was measured for a state of the art loaded epoxy matching layer at the same frequency. Reception of ultrasound without the restriction of critical angles was also achieved, and no dispersion was observed in these structures (unlike current matching layers) until at least 200 MHz. In addition, to make a significant step forward towards high frequency tissue characterisation, novel microstructured poly(vinyl alcohol) tissue-mimicking phantoms were also developed. These phantoms possessed acoustic and microstructural properties representative of fibrous tissues, much more realistic than currently used homogeneous phantoms. The attenuation coefficient measured along the direction of PVA alignment in an example phantom was 8 dBmm-1 at 30 MHz, in excellent agreement with healthy human myocardium. This method will allow the fabrication of more realistic and repeatable phantoms for future high frequency tissue characterisation studies.</p>

High Frequency Ultrasonic Wave Propagation in Anisotropic Materials

<p>The influence of highly regular, anisotropic, microstructured materials on high frequency ultrasonic wave propagation was investigated in this work. Microstructure, often only treated as a source of scattering, significantly influences high frequency ultrasonic waves, resulting in unexpected guided wave modes. Tissues, such as skin or muscle, are treated as homogeneous by current medical ultrasound systems, but actually consist of highly anisotropic micron-sized fibres. As these systems increase towards 100 MHz, these fibres will significantly influence propagating waves leading to guided wave modes. The effect of these modes on image quality must be considered. However, before studies can be undertaken on fibrous tissues, wave propagation in more ideal structures must be first understood. After the construction of a suitable high frequency ultrasound experimental system, finite element modelling and experimental characterisation of high frequency (20-200 MHz) ultrasonic waves in ideal, collinear, nanostructured alumina was carried out. These results revealed interesting waveguiding phenomena, and also identified the potential and significant advantages of using a microstructured material as an alternative acoustic matching layer in ultrasonic transducer design. Tailorable acoustic impedances were achieved from 4-17 MRayl, covering the impedance range of 7-12 MRayl most commonly required by transducer matching layers. Attenuation coefficients as low as 3.5 dBmm-1 were measured at 100 MHz, which is excellent when compared with 500 dBmm-1 that was measured for a state of the art loaded epoxy matching layer at the same frequency. Reception of ultrasound without the restriction of critical angles was also achieved, and no dispersion was observed in these structures (unlike current matching layers) until at least 200 MHz. In addition, to make a significant step forward towards high frequency tissue characterisation, novel microstructured poly(vinyl alcohol) tissue-mimicking phantoms were also developed. These phantoms possessed acoustic and microstructural properties representative of fibrous tissues, much more realistic than currently used homogeneous phantoms. The attenuation coefficient measured along the direction of PVA alignment in an example phantom was 8 dBmm-1 at 30 MHz, in excellent agreement with healthy human myocardium. This method will allow the fabrication of more realistic and repeatable phantoms for future high frequency tissue characterisation studies.</p>

Manifestations of Hepatic Focal Nodular Hyperplasia in Hepatobiliary Phase of Enhancement by Hepatocyte-specific Contrast Agent: Comparison With Pathologic Findings

Background: To explore the signals and diagnostic value of hepatic focal nodular hyperplasia (FNH) in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) enhanced MRI.Methods: Imaging data of 43 pathologically proven FNH lesions from 39 patients who underwent Gd-EOB-DTPA enhanced MRI scanning at our hospital between January 2016 and June 2019 were retrospectively analyzed. The signal characteristics in the hepatobiliary phase were analyzed and compared with the pathologic findings.Results: According to the characteristics of signals in the hepatobiliary phase, the signals were classified as follows: homogenous iso-high intensity signals in 20.93% (9/43) lesions, heterogeneous iso-high intensity signals in 67.44% (29/43) lesions, homogenous low-intensity signals in 4.65% (2/43) lesions, and heterogeneous low-intensity signals in 6.98% (3/43) lesions. Two patients were with multiple lesions, where one was with 2 lesions of heterogeneous high-intensity signals, and the other with 3 lesions of heterogeneous low-intensity signals. Pathologic findings were as follows: the slices of the 38 lesions with high-intensity signals in a hepatobiliary phase were with hyperplasic hepatocytes, inflammatory cell infiltration, and malformed blood vessels. Twenty-nine of the lesions were with fiber tissues of different degrees and were classified as classic type. The remaining 9 lesions were without fibrous scars and were classified as non-classic type. The other 5 of the 43 lesions were non-classic FNH with no evident fibrous tissues, while 4 of them were with >40% steatosis in the hyperplasic hepatocytes; the immunohistochemistry showed CK7(-)/CK19(-) in 1 lesion and β-catenin (nucleus +) in another lesion. Comparisons of pathologic with imaging findings were as follows: twenty-nine lesions were with heterogeneous iso-high intensity signals, of which the slices showed evident fibrous tissues of different degrees, and the slices of 9 lesions with homogenous iso-high intensity signals in the hepatobiliary phase showed no fibrous tissues. Three lesions with heterogeneous low-intensity signals in the hepatobiliary phase showed about 80% mixed steatosis in hyperplasic hepatocytes. The other two lesions both showed homogeneous low-intensity signals in the hepatobiliary phase, where 1 lesion was with >40% macrovesicular steatosis and CK7/CK19 (-), while the other only showed β-catenin (nucleus +) by immunohistochemistry. Conclusions: The signals of FNH in the hepatobiliary phase showed various characteristics, where the signal differences were mainly associated with the number of hyperplastic hepatocytes in lesions, presence of steatosis, fibrous scars, and conditions of small bile ducts, and potentially associated with β-catenin (nucleus+). Low-intensity signals were relatively rare for FNH, thus representing a relatively major challenge for diagnosing this type FNH.

FIBROSIS: POLYETIOLOGIC COMPLICATION WITH COMMON DENOMINATOR

State of the problem. The growth of fibrous connective tissue is a common complication of various pathological processes, which significantly complicates recovery and is one of the leading causes of death. Despite many years of research, the process of fibrosis development remains insufficiently studied and contains a large number of “white spots”. Fibrosis is characterized by unpredictability, propensity to grow and low level of the replacement by normal connective tissue. The structure of fibrous tissue, its differences from normal and the reasons for the formation of these differences deserve no less attention. The formation of fibrous tissue is preceded by the process of endogenous intoxication – the formation and accumulation of various abnormal metabolites. Among the latter, the leading place belongs to proteins and peptides, whose structure is disrupted and destabilized. It is known that destabilized proteins are prone to aggregation. This process, contrary to popular belief, is not chaotic, but is subject to certain laws and is aimed at minimizing of free energy. With regard of the latter circumstance a definite favorite is the formation of β-structured fibrils, which occupy almost the lowest energy level among protein conformational states. Such fibrils are characterized by insolubility, resistance to proteolysis, immunogenicity and the ability to autochthonous growth due to sorption and conformational rearrangement of soluble proteins. A classic example of such aggregation is amyloid formation, but there are good reasons to assume similar processes in the formation of other pathological tissues. The aim of the work was to verify experimentally the presence of β-structured protein aggregates in fibrous tissues, which differ in etiology. The methodical part included the selection of surgical material, its fixation in 10 % formaldehyde solution, preparation of Congo-stained red histological specimens and microscopic examination in light, polarization and fluorescence modes. Results. The presence of β-structured protein aggregates in fibrous tissues formed due to local chronic inflammation, viral infection and side effects of drugs has been proven experimentally. The identified phenomenon allows us to approach the understanding of the mechanisms of fibrosis development and to postulate a key role of regular aggregation of destabilized proteins. Conclusions. The obtained data testifies to a general and integral participation of β-structured protein aggregates in the formation of fibrous tissues of different etiologies. The presence of these deposits in fibrous tissues formed due to local chronic inflammation, viral infection and side effects of the cytostatic doxorubicin has been shown. The leading role of violation of protein homeostasis and local accumulation of structurally damaged proteins as a prerequisite for autochthonous aggregation process is discussed. The expediency of fluorescence microscopy has been shown, which significantly expands the possibilities of detecting with the help of the Congo red of nanosized β-structured protein aggregates, which are invisible due to Abbe's limitations in light and polarization microscopy. Key words: fibrosis, keloidosis, Peyronie’s disease, Covid-19, cytostatics, nanoparticles.

Spatial Controls of Ligamentous Tissue Orientations Using the Additively Manufactured Platforms in an In Vivo Model: A Pilot Study

The periodontal ligaments (PDLs) with specific orientations to tooth-root surfaces play a key role in generating biomechanical responses between the alveolar bone and cementum as a tooth-supporting tissue. However, control of angulations and regeneration of the ligamentous tissues within micron-scaled interfaces remains challenging. To overcome this limitation, this study investigated surface fabrications with microgroove patterns to control orientations of rat PDL cells in vitro and fibrous tissues in vivo. After being harvested, rat PDL cells were cultured and three different microgroove patterns (∠PDL groove = 0°, ∠PDL groove = 45°, and ∠PDL groove = 90°) were created by the digital slicing step in 3D printing. Cell-seeded scaffolds were subcutaneously transplanted at 3 and 6 weeks. In histology images, rat PDL cells were spatially controlled to angularly organize following the microgroove patterns and fibrous tissues were formed in scaffolds with specific angulations, which were reflected by additively manufactured microgroove topographies. Based on the results, specifically characterized surface topographies were significant to directly/indirectly organizing rat PDL cell alignments and fibrous tissue orientations. Therefore, interactions between surface topographies and tissue organizations could be one of the key moderators for the multiple tissue complex (bone-ligament-cementum) neogenesis in periodontal tissue engineering.

Laparoscopic Diagnosis and Treatment of Gossypiboma Postconventional Ovariohysterectomy in a Bitch

Introduction. Gossypiboma is a rare surgical complication in small animals. The authors reported the laparoscopic diagnosis and treatment of an abdominal gossypiboma and chronic draining fistula postopen ovariohysterectomy (OVH) unresponsive to medical treatment in a bitch. Case Presentation. The patient had undergone OVH and exploratory laparotomy in other veterinary practice 3 years previously. The animal, presenting a chronic fistula, was then referred to UFSM Veterinary Hospital. Ultrasonographic examination revealed a structure compatible with a granuloma. For the laparoscopic procedure, a 3-port (two at 11 mm; one at 6 mm) access was used. Adhesiolysis and mass removal were performed by blunt dissection and bipolar electrocoagulation. The fistula was treated by mobilising the omentum through it. There were no intra- or postoperative complications. The chronic wound showed first intention healing. The mass was composed of fibrous tissues surrounding one surgical gauze. Discussion and Conclusion. The removal of a retained surgical gauze in the abdomen by laparoscopy has already been described in medicine. However, a laparoscopic approach for treating a fistulous draining tract due to a gossypiboma has not been previously reported in dogs. Laparoscopic exploration of the fistula allowed the use of a pedicled omental flap through infected sites to control chronic infection. Laparoscopic surgery can be used to identify and treat abdominal gossypiboma in dogs, including those with chronic abdominal sinus.

Hoffa’s Osteochondroma - Para-articular Extrasynovial Infrapatellar Fat Pad Osteochondroma: A Case Report

Osteochondroma usually arises from the metaphyseal region of growing bones. The occurrence of extraskeletal osteochondroma is rare with very few case reports. Para-articular osteochondroma is a type of extraskeletal osteochondroma. It frequently occurs around the knee, usually at infrapatellar Hoffa’s fat pad. It is usually intracapsular but extrasynovial and arises from the capsule and connective tissues due to osteocartilaginous metaplasia. We present a case of 19-years male with anterior knee pain for 3 years, swelling, and deformity of the knee with flexion limitation for one year. Radiography revealed ovoid, corticated lesion free from adjoining bones. Mass interpreted as benign, so planned for excision. Well circumscribed nodule excised from the medial parapatellar approach. Histology revealed cartilaginous tissues surrounded by fibrous tissues with scattered enchondral ossification.Postoperatively and subsequent follow-up resulted in pain-free joint, complete recovery of range of motion with no clinicoradiological evidence of recurrence.

How Structural Features of a Spring-Based Model of Fibrous Collagen Tissue Govern the Overall Young's Modulus

While much study has been dedicated to investigating biopolymers' stress-strain response at low strain levels, little research has been done to investigate the linear region of biopolymers' stress-strain response and how the microstructure affects it. We propose a mathematical model of fibrous networks which reproduces qualitative features of collagen gel's stress-strain response and provides insight into the key features which impact the Young's Modulus of similar fibrous tissues. This model analyzes the relationship of the Young's Modulus of the lattice to internodal fiber length, number of connection points or nodes per unit area, and average number of connections to each node. Our results show that fiber length, nodal density, and level of connectivity each uniquely impact the Young's Modulus of the lattice. Furthermore, our model indicates that the Young's Modulus of a lattice can be estimated using the effective resistance of the network, a graph theory technique that measures distances across a network. Our model thus provides insight into how the organization of fibers in a biopolymer impact its linear Young&#39;s Modulus.