Soft Tissue Growth Research Articles

Adaptive integration of history variables in constrained mixture models for organ-scale growth and remodeling.

In the last decades, many computational models have been developed to predict soft tissue growth and remodeling (G&R). The constrained mixture theory describes fundamental mechanobiological processes in soft tissue G&R and has been widely adopted in cardiovascular models of G&R. However, even after two decades of work, large organ-scale models are rare, mainly due to high computational costs (model evaluation and memory consumption), especially in long-range simulations. We propose two strategies to adaptively integrate history variables in constrained mixture models to enable large organ-scale simulations of G&R. Both strategies exploit that the influence of deposited tissue on the current mixture decreases over time through degradation. One strategy is independent of external loading, allowing the estimation of the computational resources ahead of the simulation. The other adapts the history snapshots based on the local mechanobiological environment so that the additional integration errors can be controlled and kept negligibly small, even in G&R scenarios with severe perturbations. We analyze the adaptively integrated constrained mixture model on a tissue patch for a parameter study and show the performance under different G&R scenarios. To confirm that adaptive strategies enable large organ-scale examples, we show simulations of different hypertension conditions with a real-world example of a biventricular heart discretized with a finite element mesh. In our example, adaptive integrations sped up simulations by a factor of three and reduced memory requirements to one-sixth. The reduction of the computational costs gets even more pronounced for simulations over longer periods. Adaptive integration of the history variables allows studying more finely resolved models and longer G&R periods while computational costs are drastically reduced and largely constant in time.

Multiscale homogenized constrained mixture model of the bio-chemo-mechanics of soft tissue growth and remodeling.

Constrained mixture models have successfully simulated many cases of growth and remodeling in soft biological tissues. So far, extensions of these models have been proposed to include either intracellular signaling or chemo-mechanical coupling on the organ-scale. However, no version of constrained mixture models currently exists that includes both aspects. Here, we propose such a version that resolves cellular signal processing by a set of logic-gated ordinary differential equations and captures chemo-mechanical interactions between cells by coupling a reaction-diffusion equation with the equations of nonlinear continuum mechanics. To demonstrate the potential of the model, we present 2 case studies within vascular solid mechanics: (i) the influence of angiotensin II on aortic growth and remodeling and (ii) the effect of communication between endothelial and intramural arterial cells via nitric oxide and endothelin-1.

Periosteum response to static forces stimulates cortical drifting: A new orthopedic target

The mechanism of cortical bone adaptation to static forces is not well understood. This is an important process because static forces are applied to the cortical bone in response to the growth of soft tissues and during Orthodontic and Orthopedic corrections. The aim of this study was to investigate the cortical bone response to expanding forces applied to the maxilla. Overall, 375 adult Sprague-Dawley rats were divided into three groups: 1) static force group, 2) static force plus stimulation group, and 3) sham group. In addition to static force across the maxilla, some animals were exposed to anti-inflammatory medication. Samples were collected at different time points and evaluated by micro-computed tomography, fluorescence microscopy, immunohistochemistry, and gene and protein analyses. The application of expansion forces to the maxilla increased inflammation in the periosteum and activated osteoclasts on the surface of the cortical plate. This activation was independent of the magnitude of tooth movement but followed the pattern of skeletal displacement. Bone formation on the surface of the cortical plate occurred at a later stage and resulted in the relocation of the cortical boundary of the maxilla and cortical drifting. This study demonstrates that cortical bone adaptation to static forces originates from the periosteum, and it is an inflammatory-based phenomenon that can be manipulated by the clinician. Our findings support a new theory for cortical adaptation to static forces and an innovative clinical approach to promote cortical drifting through periosteal stimulation. Being able to control cortical drift can have a significant impact on clinical orthodontic and dentofacial orthopedics by allowing corrections of severe deformities without the need for maxillofacial surgery.

Phage embedded gelatin, alginate and gelatin/alginate-starch based hydrogels for topical bactericidal applications against multi-drug resistant Pseudomonas aeruginosa

Topical phage administration through hydrogels is one of the most efficient ways to inhibit bacterial growth in soft tissues. Hydrogels can benefit the skin by acting as a barrier and also promote tissue regeneration and moisture retention in cases of skin breach. Hydrogels incorporated with bioactive ingredients (BAC) have found their way into skin applications ranging from pharmaceutical to cosmetic products, whereas, phage incorporated hydrogels have been under-explored. In this study, we developed gelatin (protein-based) and alginate (polysaccharide-based) hydrogels (GH & AH) to immobilize phages for topical antibacterial treatments. P. aeruginosa is a common wound infecting pathogen and the strain ATCC 15442 used in this study is a β-lactamase producing multi-drug resistant variant. Gelatin and alginate are natural polymers and were chemically crosslinked (covalent & ionic interactions) to develop matrices that embed phages. Aloe vera extracts were used to synthesize hydrogels to succor the healing process. Starch-incorporated gelatin and alginate gels were also screened for phage immobilization. The addition of starch adversely affected the porosity of the matrices but did not affect the swelling ratio of the hydrogels. SEM analysis revealed porous microstructure of gelatin and alginate hydrogel, where starch addition resulted in cracked surface topography. All the developed hydrogels were amorphous in nature, lacking a regular pattern in the structural orientation of the molecules. Phages were successfully administered into the matrix after hydrogel synthesis through absorption. The swelling ratio of gelatin and alginate hydrogels were 2.6 and 0.5 g/g at 30 min. Phages released in buffer at 30 min were 1.6 x 107 and 2.6 x 106 PFU/mL for gelatin and alginate hydrogels respectively. The antibacterial evaluation of phage-incorporated gels showed a zone of inhibition against phage specific P. aeruginosa in agar plates.

An Enigmatic Soft-Tissue Creeping Phenomenon: The Spontaneous Peri-Implant Mucosa Margin and Papilla Growth, Part Two-A Scientifically Supported Hypothesis Article.

In our previous article, we observed and measured a spontaneous growth in the coronal direction of the keratinized tissues present around implants. This growth involved both free margins and interdental papillae, and we indicated our hypothesis on the probable cause of this still-unexplained phenomenon. The growth of oral soft tissues involves several other structures, such as the linea alba and tongue indentation. Our idea holds that growth of these tissues is generated by the negative intraoral pressure created in the oral phase of swallowing and the subsequent resting position, which through the resulting suction causes a shift of these soft structures in the gaps around the dental crowns. Other hypotheses have been suggested in the past to understand this phenomenon of soft tissue growth, which still lacks data supporting etiological evidence. The purpose of this article is to thoroughly analyze and verify our model by comparing the clinical observations with citations and examples from the literature, combined with notions of physiology, biology, and physics that help in clarifying these events. To better explain the mechanisms of oral soft tissue growth, photographs of clinical cases paradigmatic of the phenomenon are shown.

Melorheostosis (Leri's Disease): A Review.

Melorheostosis is a noncancerous bone disease characterized by abnormal bone and soft tissue growth. Despite being identified almost a century ago, there are still many unknown aspects surrounding this condition. It can often be an incidental discovery, with patients experiencing associated pain and deformities. Diagnosis typically relies on X-rays, although not all cases exhibit the classic candle wax appearance. A new imaging sign known as the "dumpling on a plate sign" has been proposed for flat bones for both MRI and CT scans. A biopsy may be necessary in cases of uncertainty, as there is not a definitive histological feature. It is not uncommon for melorheostosis to be linked with other conditions, and a collaborative approach involving a multidisciplinary team should be considered. This condition should be considered in the differential diagnosis of sclerotic bone conditions. Management is generally aimed at symptom relief, either through conservative measures or surgical intervention.

Neglected Spheno-orbital Meningioma Presenting with Unilateral Blindness

Sphenoorbital meningiomas (SOM) constitutes 9% of all intracranial meningiomas and are originated from sphenoid wing dura. They are also called en plaque meningioma. They cause hyperostosis of involved bone and their soft tissue growth may spread the orbit, the infratemporal fossa, and the temporal fossa. Most patients with SOM are middle- aged women and most commonly presents with unilateral, nonpulsating, progressive proptosis. Recently a woman with unilateral progressive proptosis from a remote area of Bangladesh presented to us with blindness of her left eye due to diagnostic delay. After thorough evaluation and imaging studies, she was diagnosed with a large spheno-orbital meningioma with extensive bony involvement of skull base and orbit. Objective: This report highlights the necessity of creating awareness among optometrists, undergraduate medical students as well as and ophthalmologists who are practicing in remote areas of Bangladesh about clinical presentation of sphenoorbital meningiomas which is a benign lesion but may be a cause of unilateral blindness if remain undiagnosed for long Bang. J Neurosurgery 2023; 13(1): 51-54

A mixed trigger volumetric growth law for cylindrical deformation in stressed configurations

Soft tissue growth is crucial across various physiological applications, with mathematical modelling playing a pivotal role in understanding the underlying processes. The volumetric growth theory serves as a commonly used mathematical framework in this context. Our previous research on volumetric growth theory primarily concentrated on defining the incremental growth tensor in loaded and stressed configurations, revealing that this approach closely aligns with experimental observations of residual hoop stress distribution. However, given the assumptions employed, the approach has limitations in accurately predicting the growth timeline. In this work, we address these issues by incorporating the effect of initial residual strain and introducing a new mixed trigger growth evolution law. In this growth law, we do not use growth saturation as an upper limit, as this assumption cannot represent many physiological conditions. Instead, we propose that growth in soft tissues leads to a new equilibrium state. To illustrate this idea, we introduce a growth incompatibility function, denoted as I . We establish the analytical relationship between I and the opening angle in a simplified cylindrical geometry resembling the structure of the heart or arteries. We put forth a revised growth law that is both stress and incompatibility driven/Our results show that by using this mixed trigger growth law, tissues will not grow indefinitely. Instead, a stress-driven homeostasis incompatibility state will be reached. In addition, by accounting for the initial opening angle in the model, we can accurately trace the growth history of the heart, aligning with experimental data obtained from measuring the opening angle in young pigs from birth to maturity.

Mucocele in the Posterior Mucogingival Region of Mandibula: a Rare Case Report

Mucocele means a cavity filled with mucus. These lesions, which are the second most common soft tissue growth in the mouth, mostly originate from minor salivary glands. A 30-year-old female patient was admitted to our clinic. On examination, an asymptomatic lesion was detected in the right premolar region of the mandible, which was fluctuant on palpation and similar in color to the surrounding tissues. After surgical removal of the lesion, a diagnosis of mucocele was made after histopathologic examination. Mucoceles are frequently seen in the lower lip, they can rarely be observed in many areas of the intraoral region where the minor salivary glands are located. No case of mucocele in the mandibular premolar region, especially in the mucogingival area, was found in the literature.

High temperatures alter the patterns of growth and development and cause physiological and biochemical stresses in Chinese cyclina Cyclina sinensis

Prolonged high temperature is a critical environmental factor contributing to the mass mortality of clams in summer. We investigated the growth and development of Cyclina sinensis cultured at different temperatures (25, 28, 31, and 34 °C) and their physiological and biochemical responses following a long period of exposure. The mortality rates at 31 °C and 34 °C were significantly higher than at 25 °C and 28 °C after 48 d (P < 0.05). The overall survival rates at 25 °C and 28 °C did not differ significantly from the control group (at natural seawater temperature), but were significantly lower at 31 °C and 34 °C (P < 0.05). The growth parameters of C. sinensis in all of the experimental groups were significantly higher than in the control group (P < 0.05), with the highest specific growth rate at 28 °C. The shell to soft tissue ratio was greatly increased in the 31 °C and 34 °C groups and was significantly higher than in the other groups after 32 d (P < 0.05). The condition factor at 28 °C was significantly higher than in the other groups (P < 0.05), and started to decline after 32 days at 31 °C and 34 °C. The hepatopancreatic and gonadotropic indexes were significantly lower at 31 °C and 34 °C than in the control group (P < 0.05). Appropriate temperature rises increased the filtration rate and ingestion rate but these were clearly inhibited at 31 °C and 34 °C. The activities of superoxide dismutase, catalase, acid phosphatase (ACP), and lysozyme (LZM) were significantly reduced at 31 °C and 34 °C (P < 0.05). The activities of ACP, LZM, amylase, and the proteases were significantly increased at 28 °C (P < 0.05). Our study showed that high temperatures accelerate the growth of shells but inhibit the growth of soft tissues, negatively affecting the development, physiology, and biochemistry of C. sinensis. Cyclina sinensis demonstrates better overall performance at 28 °C, but aquaculture production would be severely affected if the temperature reaches, or exceeds 31 °C.

Carotidynia: Overview of an uncommon identification for unilateral neck pain.

Carotidynia, also known as Fay Syndrome, manifests as an atypical facial neuralgia characterized by an unusual neck pain extending towards the head and associated with carotid artery tenderness. Diagnostic criteria include neck tenderness, elevated carotid pulse without anatomical abnormalities, and neck distension. It was initially classified as a vascular headache but later re-evaluated and reclassified as a nonentity-a general condition caused by nonvascular factors. The etiology has not been extensively elucidated. We present two cases characterized by dysphagia, intermittent discomfort, and numbness in the throat and cervical region. Although the neurological examinations yielded no abnormalities, the diagnosis of carotidynia was ultimately established among the differential diagnoses upon the identification of wall thickening and inflammatory alterations through neuroimaging. Carotidynia is consistent with idiopathic vasculitis near the distal common carotid artery. Inflammatory processes trigger sympathetic plexus stimulation, causing discomfort in the head and neck. Neuroimaging resolves ambiguities in idiopathic unilateral neck pain, detecting soft tissue growth near the carotid artery. "Carotidynia" now refers to a diagnostic symptom and clinical entity encompassing a variety of disorders; therefore, approach to definition remains controversial. This report aims to raise healthcare awareness by highlighting two different cases of carotidynia.

A Cauliflower-like Growth on the Anterior Mandibular Gingivae

Abstract Verruciform xanthoma (VX) is a rare, benign, soft-tissue growth, mostly affecting the oral cavity. The distinguishing feature in its diagnosis is the occurrence of foam cells in the papillary connective tissue. The growth typically resembles a malignant tumor; therefore, the clinical presentation may be deceiving. The histopathological confirmation of the diagnosis is, therefore, crucial. Once entirely removed, there is a low likelihood of recurrence. Here, we describe a 60-year-old woman’s case with VX on the mandibular gingiva.

Growth and morphogenesis of an everted tubular biological tissue

Eversion, a ubiquitous phenomenon in living organisms, significantly contributes to the growth and morphogenesis of soft biological tissues and organs. In this study, we examine the role of elasticity and geometry in the morphogenesis of everted tubular biological tissues, both theoretically and experimentally. Our findings demonstrate that the morphogenesis of an everted tubular tissue is primarily influenced by its elasticity and geometry. Through linear stability analysis, we show that an everted bilayer tubular tissue, with isotropic differential growth, can generate a circumferential or two-dimensional pattern, but fails to produce an axial pattern, which distinguishes it from a bilayer tubular tissue without eversion. Furthermore, as the modulus ratio and layer thicknesses increase, the surface instability pattern transitions from a two-dimensional pattern to a circumferential pattern. Notably, when the modulus ratio or layer thickness reaches sufficiently high values, spontaneous instabilities emerge on the inner surface of the everted bilayer tubular tissues pre-growth. To investigate the morphological instability of everted bilayer tubes, we perform a series of quantificational finite-element simulations and swelling experiments. The results of both numerical simulations and experimental observations align well with our theoretical analysis. This study not only enhances our comprehension of everted tubular tissue morphogenesis but also offers valuable insights for biomedical engineering and growth self-assembly applications.

Exuberant circumferential fibroproliferative neuromas in lipomatosis of nerve: a unifying theory. Illustrative case.

Lipomatosis of nerve (LN) is a rare disorder characterized by the massive enlargement of peripheral nerves, frequently accompanied by generalized fibroadipose proliferation and skeletal overgrowth. The authors have been routinely following a 20-year-old male for lipomatosis of median nerve at the wrist noted shortly after birth. He had undergone resection of the lesion accompanied by sural nerve grafting at another institution. Clinically, although his neurological loss of function has been stable, he has had continued soft tissue growth. Serial magnetic resonance imaging has revealed persistent LN proximal to the repair sites with evidence of fatty proliferation in the sural grafts and continued LN and fatty proliferation distally. There has been a progressive circumferential pattern of fibrosis around the proximal and distal suture lines, which has a similar radiological pattern to desmoid type fibromatosis (a pattern recently described in neuromuscular choristoma [NMC] desmoid-type fibromatosis). Considering the similar reaction of nerve in both LN and NMC despite differing genetic cascades, the authors believe a unifying process occurs in both lesions. The pattern of circumferential fibroproliferation would be most consistent with neuron-mediated growth from unspecified trophic factors, supporting a previously reported a nerve-derived "inside-out mechanism." The clinical consequences of this unifying process are presented.

X-ray phase contrast reveals soft tissue and shell growth lines in mollusks

High-resolution 3D imaging of species with exoskeletons such as shell-bearing mollusks typically involves destructive steps. Nondestructive alternatives are desirable since samples can be rare and valuable, and destructive steps are time-consuming and may distort the tissue. Here, we show for the first time that propagation-based phase-contrast X-ray imaging can significantly increase contrast in mollusks with intact shells. By using the recently upgraded monochromator at the SPring-8 BL20B2 synchrotron beamline, we imaged six species of mollusks, showing that X-ray phase contrast enhances soft-tissue contrast. Features that are almost invisible in conventional attenuation-based micro-computed tomography (micro-CT) are clearly reproduced with phase-contrast imaging under the same scan conditions. Furthermore, this method can reveal features such as growth rings in the shell and differentiate between calcite and aragonite crystal forms. Phase-contrast imaging can thus serve as a compelling alternative when destructive methods are not an option.

Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration.

Clinical bone-morphogenetic protein 2 (BMP2) treatment for bone regeneration, often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems, necessitates research into improved biomaterials for better BMP2 stability and retention. To tackle this challenge, we introduced a groundbreaking bone-targeted, lipoplex-loaded, three-dimensional bioprinted bilayer scaffold, termed the polycaprolactone-bioink-nanoparticle (PBN) scaffold, aimed at boosting bone regeneration. We encapsulated BMP2 within the fibroin nanoparticle based lipoplex (Fibroplex) and functionalized it with DSS6 for bone tissue-specific targeting. 3D printing technology enables customized, porous PCL scaffolds for bone healing and soft tissue growth, with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex, shown to support effective nutrient exchange and cell growth at specific pore sizes. The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue, a finding validated by in vitro osteogenic differentiation assays. The PBN scaffold was evaluated for critical calvarial defects, focusing on sustained BMP2 delivery, prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo. The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge, promoting osteogenic differentiation and bone regeneration in a calvarial defect animal. Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation, thereby reducing the risk of heterotopic ossification.

Phenotypic plasticity for improved light harvesting, in tandem with methylome repatterning in reef-building corals.

Acclimatization through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms' performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant-like properties. They are light dependent with a sessile and modular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes within the colony. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally advance our understanding of how reef-building corals repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts.

Evolution of fiber distributions in homogenized constrained mixture models of soft tissue growth and remodeling: Uniaxial loading

Growth and remodeling in soft tissue changes, in general, the orientation distribution of the collagen fibers in the tissue. So far, the governing principles are still incompletely understood. In this paper, we derive from the homogenized constrained mixture theory of soft tissue growth and remodeling – under some simplifying assumptions – a theoretical framework that enables simple analytical solutions that help to understand the evolution of the collagen fiber distribution in soft tissues during growth and remodeling under uniaxial loading. Our analysis suggests a natural tendency of the collagen fiber distribution to form a peak in the direction of loading and a spread increasing with the ratio of the fiber half-life time and the time constant governing loading-related fiber production. This observation helps to understand why in vivo collagen fiber reinforcement is typically organized in the form of (often von Mises-like) distributions with a finite spread. Our analysis also suggests a considerable history dependence of the fiber distribution evolution, which may explain why, in tissues under the same type of loading, sometimes considerably different fiber orientation distributions are observed.

3D morphological changes of the lip and face in patients with cleft lip and alveolus: The comparison of the lip development of incomplete and complete cleft lips under 3 months of age

AbstractTo treat cleft lip and palate, it is critical to understand the development of the lips and face.ObjectiveThe objective of this study is to comprehend the development of lips and facial features in patients with cleft lip from birth to cheiloplasty. A comparison of incomplete and complete cleft lips was performed.MethodsThe morphology of the lips and face was recorded using a noncontact three‐dimensional morphology recorder from shortly after birth to cheiloplasty. For each patient, their soft tissue growth was analyzed.ResultsThese findings suggest that an incomplete cleft widens the gap between healthy and affected sides from 2 to 3 months of age. The pattern is different from that of a complete cleft.

Enhanced BMP signaling in Cathepsin K-positive tendon progenitors induces heterotopic ossification

Heterotopic ossification (HO) is abnormal bone growth in soft tissues that results from injury, trauma, and rare genetic disorders. Bone morphogenetic proteins (BMPs) are critical osteogenic regulators which are involved in HO. However, it remains unclear how BMP signaling interacts with other extracellular stimuli to form HO. To address this question, using the Cre-loxP recombination system in mice, we conditionally expressed the constitutively activated BMP type I receptor ALK2 with a Q207D mutation (Ca-ALK2) in Cathepsin K-Cre labeled tendon progenitors (hereafter “Ca-Alk2:Ctsk-Cre”). Ca-Alk2:Ctsk-Cre mice were viable but they formed spontaneous HO in the Achilles tendon. Histological and molecular marker analysis revealed that HO is formed via endochondral ossification. Ectopic chondrogenesis coincided with enhanced GLI1 production, suggesting that elevated Hedgehog (Hh) signaling is involved in the pathogenesis of HO. Interestingly, focal adhesion kinase, a critical mediator for the mechanotransduction pathway, was also activated in Ca-Alk2:Ctsk-Cre mice. Our findings suggest that enhanced BMP signaling may elevate Hh and mechanotransduction pathways, thereby causing HO in the regions of the Achilles tendon.