There is an unmet need for a consistent set of tools for the evaluation of 3D‐printed constructs. A toolbox developed to design, characterize, and evaluate 3D‐printed poly(propylene fumarate) ...scaffolds is proposed for vascularized engineered tissues. This toolbox combines modular design and non‐destructive fabricated design evaluation, evaluates biocompatibility and mechanical properties, and models angiogenesis.
An accurate
in vitro
model of human adipose tissue could assist in the study of adipocyte function and allow for better tools for screening new therapeutic compounds. Cell culture models on ...two-dimensional surfaces fall short of mimicking the three-dimensional
in vivo
adipose environment, while three-dimensional culture models are often unable to support long-term cell culture due, in part, to insufficient mass transport. Microfluidic systems have been explored for adipose tissue models. However, current systems have primarily focused on 2D cultured adipocytes. In this work, a 3D human adipose microtissue was engineered within a microfluidic system. Human adipose-derived stem cells (ADSCs) were used as the cell source for generating differentiated adipocytes. The ADSCs differentiated within the microfluidic system formed a dense lipid-loaded mass with the expression of adipose tissue genetic markers. Engineered adipose tissue showed a decreased adiponectin secretion and increased free fatty acid secretion with increasing shear stress. Adipogenesis markers were downregulated with increasing shear stress. Overall, this microfluidic system enables the on-chip differentiation and development of a functional 3D human adipose microtissue supported by the interstitial flow. This system could potentially serve as a platform for
in vitro
drug testing for adipose tissue-related diseases.
This work presents a microfluidic system for the engineering and analysis of 3D human adipose tissue under controlled flow.
Laminins in metabolic tissues Goddi, Anna; Schroedl, Liesl; Brey, Eric M. ...
Metabolism, clinical and experimental,
07/2021, Letnik:
120
Journal Article
Recenzirano
Laminins are extracellular matrix proteins that reside in the basement membrane and provide structural support in addition to promoting cellular adhesion and migration. Through interactions with cell ...surface receptors, laminins stimulate intracellular signaling cascades which direct specific survival and differentiation outcomes. In metabolic tissues such as the pancreas, adipose, muscle, and liver, laminin isoforms are expressed in discrete temporal and spatial patterns suggesting that certain isoforms may support the development and function of particular metabolic cell types. This review focuses on the research to date detailing the expression of laminin isoforms, their potential function, as well as known pathways involved in laminin signaling in metabolic tissues. We will also discuss the current biomedical therapies involving laminins in these tissues in addition to prospective applications, with the goal being to encourage future investigation of laminins in the context of metabolic disease.
•Laminins are extracellular matrix proteins that play diverse roles in metabolic tissues.•Adipose tissue laminins regulate energy expenditure and insulin sensitivity.•Pancreatic laminins appear to promote insulin secretion and β-cell proliferation.•Altered laminin expression is seen in metabolic disorders such as insulin resistance and obesity.•Due to their extracellular location, laminins may be inviting targets for the treatment of metabolic disorders.
Abstract Vascularization of biomaterial scaffolds is essential for the successful clinical application of engineered tissues. Experimental studies are often performed to investigate the role of ...scaffold architecture on vascularized tissue formation. However, experiments are expensive and time-consuming and synthesis protocols often do not allow for independent investigation of specific scaffold properties. Computational models allow for rapid screening of potential material designs with control over scaffold properties that is difficult in laboratory settings. We have developed and tested a three-dimensional agent-based framework for investigating the effect of scaffold pore architecture on angiogenesis. Software agents represent endothelial cells, interacting together and with their micro-environment, leading to the invasion of blood vessels into the scaffold. A rule base, driven by experimental findings, governs the behavior of individual agents. 3D scaffold models with well-defined homogeneous and heterogeneous pore architectures were simulated to investigate the impact of various design parameters. Simulation results indicate that pores of larger size with higher interconnectivity and porosity support rapid and extensive angiogenesis. The developed framework can be used to screen biomaterial scaffold designs for optimal vascularization and investigate complex interactions among invading blood vessels and their micro-environment.
Abstract Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The ...unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research. Traditionally, histological and immunohistochemical techniques have been used to evaluate engineered tissues. However, these methods do not allow for an accurate volume assessment, are invasive, and do not provide information on functional status. Imaging techniques are needed that enable non-destructive, longitudinal, quantitative, and three-dimensional analysis of TERM strategies. This review focuses on evaluating the application of available imaging modalities for assessment of biomaterials and tissue in TERM applications. Included is a discussion of limitations of these techniques and identification of areas for further development.
Abstract The importance of vascularization in the field of bone tissue engineering has been established by previous studies. The present work proposes a novel poly(propylene fumarate) (PPF)/fibrin ...composite scaffold for the development of vascularized neobone tissue. The effect of prevascularization (i.e., in vitro pre-culture prior to implantation) with human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on in vivo vascularization of scaffolds was determined. Five conditions were studied: no pre-culture (NP), 1 week pre-culture (1P), 2 week pre-culture (2P), 3 week pre-culture (3P), and scaffolds without cells (control, C). Scaffolds were implanted subcutaneously in a severe combined immunodeficiency (SCID) mouse model for 9 days. During in vitro studies, CD31 staining showed a significant increase in vascular network area over 3 weeks of culture. Vascular density was significantly higher in vivo when comparing the NP and 3P groups. Immunohistochemical staining of human CD-31 expression indicated spreading of vascular networks with increasing pre-culture time. These vascular networks were perfused with mouse blood indicated by perfused lectin staining in human CD-31 positive vessels. Our results demonstrate that in vitro prevascularization supports in vivo vascularization in PPF/fibrin scaffolds.
Porous hydrogels of poly(ethylene glycol) (PEG) have been shown to facilitate vascularized tissue formation. However, PEG hydrogels exhibit limited degradation under physiological conditions which ...hinders their ultimate applicability for tissue engineering therapies. Introduction of poly(L-lactic acid) (PLLA) chains into the PEG backbone results in copolymers that exhibit degradation via hydrolysis that can be controlled, in part, by the copolymer conditions. In this study, porous, PEG-PLLA hydrogels were generated by solvent casting/particulate leaching and photopolymerization. The influence of polymer conditions on hydrogel architecture, degradation and mechanical properties was investigated. Autofluorescence exhibited by the hydrogels allowed for three-dimensional, non-destructive monitoring of hydrogel structure under fully swelled conditions. The initial pore size depended on particulate size but not polymer concentration, while degradation time was dependent on polymer concentration. Compressive modulus was a function of polymer concentration and decreased as the hydrogels degraded. Interestingly, pore size did not vary during degradation contrary to what has been observed in other polymer systems. These results provide a technique for generating porous, degradable PEG-PLLA hydrogels and insight into how the degradation, structure, and mechanical properties depend on synthesis conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endothelialization mechanisms in vascular grafts Sánchez, Paolo F.; Brey, Eric M.; Briceño, Juan Carlos
Journal of tissue engineering and regenerative medicine,
November 2018, 2018-Nov, 2018-11-00, 20181101, Letnik:
12, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Despite the wide variety of tissue‐engineered vascular grafts that are currently being developed, autologous vessels, such as the saphenous vein, are still the gold standard grafts for surgical ...treatment of vascular disease. Recently developed technologies have shown promising results in preclinical studies, but they still do not overcome the issues that native vessels present, and only a few have made the transition into clinical use. The endothelial lining is a key aspect for the success or failure of the grafts, especially on smaller diameter grafts (<5 mm). However, during the design and evaluation of the grafts, the mechanisms for the formation of this layer are not commonly examined. Therefore, a significant amount of established research might not be relevant to the clinical context, due to important differences that exist between the vascular regeneration mechanisms found in animal models and humans. This article reviews current knowledge about endothelialization mechanisms that have been so far identified: in vitro seeding, transanastomotic growth, transmural infiltration, and fallout endothelialization. Emphasis is placed on the models used for study of theses mechanisms and their effects on the development of tissue‐engineering vascular conduits.
Delivery of compounds to the peripheral nervous system has the potential to be used as a treatment for a broad range of conditions and applications, including neuropathic pain, regional anesthesia, ...traumatic nerve injury, and inherited and inflammatory neuropathies. However, efficient delivery of therapeutic doses can be difficult to achieve due to peripheral neuroanatomy and the restrictiveness of the blood-nerve barrier. Depending on the underlying integrity of the blood-nerve barrier in the application at hand, several strategies can be employed to navigate the peripheral nerve architecture and facilitate targeted delivery to the peripheral nerve. This review describes different applications where targeted delivery to the peripheral nervous system is desired, the challenges that the blood-nerve barrier poses in each application, and bioengineering strategies that can facilitate delivery in each application.
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