scholarly journals In vivo sequestration of innate small molecules to promote bone healing

2019 ◽  
Author(s):  
Yuze Zeng ◽  
Yu-Ru V. Shih ◽  
Gurpreet S. Baht ◽  
Shyni Varghese
Keyword(s):  
Small Molecules ◽  
Human Body ◽  
Tissue Repair ◽  
Physiological Level ◽  
Extracellular Adenosine ◽  
Injury Site ◽  
Synthetic Biomaterial ◽  
Repair Mechanisms

AbstractApproaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, we describe biomaterial-assisted sequestration of small molecules to localize pro-regenerative signaling at the injury site. Specifically, we designed a synthetic biomaterial containing boronate molecules to sequester adenosine, a small molecule ubiquitously present in the human body. The biomaterial-assisted sequestration of adenosine leverages the transient surge of extracellular adenosine following injury to prolong local adenosine signaling. We demonstrated that implantation of the biomaterial patch following injury establishes an in-situ stockpile of adenosine, resulting in accelerated healing by promoting both osteoblastogenesis and angiogenesis. The adenosine content within the patch recedes to the physiological level as the tissue regenerates. In addition to sequestering endogenous adenosine, the biomaterial is also able to deliver exogenous adenosine to the site of injury, offering a versatile solution to utilizing adenosine as a potential therapeutic for tissue repair.

scholarly journals Seeing Better and Going Deeper in Cancer Nanotheranostics

2019 ◽  
Vol 20 (14) ◽  
pp. 3490 ◽  
Author(s):  
Maharajan Sivasubramanian ◽  
Yao Chen Chuang ◽  
Nai-Tzu Chen ◽  
Leu-Wei Lo
Keyword(s):  
Clinical Practice ◽  
Early Diagnosis ◽  
Contrast Agents ◽  
Human Body ◽  
State Of The Art ◽  
Specific Accumulation ◽  
Appropriate Therapy ◽  
Disease Specific

Biomedical imaging modalities in clinical practice have revolutionized oncology for several decades. State-of-the-art biomedical techniques allow visualizing both normal physiological and pathological architectures of the human body. The use of nanoparticles (NP) as contrast agents enabled visualization of refined contrast images with superior resolution, which assists clinicians in more accurate diagnoses and in planning appropriate therapy. These desirable features are due to the ability of NPs to carry high payloads (contrast agents or drugs), increased in vivo half-life, and disease-specific accumulation. We review the various NP-based interventions for treatments of deep-seated tumors, involving “seeing better” to precisely visualize early diagnosis and “going deeper” to activate selective therapeutics in situ.

scholarly journals A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury

2015 ◽  
Vol 212 (4) ◽  
pp. 447-456 ◽  
Author(s):  
Daniela Dal-Secco ◽  
Jing Wang ◽  
Zhutian Zeng ◽  
Elzbieta Kolaczkowska ◽  
Connie H.Y. Wong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Hepatic Injury ◽  
Dynamic Spectrum ◽  
Fluorescent Reporters ◽  
Injured Area ◽  
A Site ◽  
Local Cytokine

Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2hiCX3CR1low) and nonclassical, patrolling, or alternative (CCR2lowCX3CR1hi) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2hiCX3CR1low monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2hiCx3CR1low to CX3CR1hiCCR2low within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing.

scholarly journals Click by Click Microporous Annealed Particle (MAP) Scaffolds

2019 ◽  
Author(s):  
Nicole J. Darling ◽  
Weixian Xi ◽  
Elias Sideris ◽  
Alexa Anderson ◽  
Cassie Pong ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Maximum Stress ◽  
Porous Scaffold ◽  
Click Reaction ◽  
Dermal Fibroblasts ◽  
Hydrogel Microparticles ◽  
Assembly Method ◽  
Key Issues

AbstractMacroporous scaffolds are being increasingly used in regenerative medicine and tissue repair. While our recently developed microporous annealed particle (MAP) scaffolds have overcome issues with injectability and in situ hydrogel formation, limitations with respect to tunability to be able to manipulate hydrogel strength and rigidity for broad applications still exist. To address these key issues, here we synthesized hydrogel microparticles (HMPs) of hyaluronic acid (HA) using the thiol-norbornene click reaction and then subsequently annealed HMPs into a porous scaffold using the tetrazine-norbornene click reaction. This assembly method allowed for straightforward tuning of bulk scaffold rigidity by varying the tetrazine to norbornene ratio, with increasing tetrazine resulting in increasing scaffold storage modulus, Young’s modulus, and maximum stress. These changes were independent of void fraction. Further incorporation of human dermal fibroblasts (HDFs) throughout the porous scaffold revealed the biocompatibility of this annealing strategy as well as differences in proliferation and cell-occupied volume. Finally, injection of porous HA-Tet MAP scaffolds into an ischemic stroke model showed this chemistry is biocompatible in vivo with reduced levels of inflammation and astrogliosis as previously demonstrated for other crosslinking chemistries.

scholarly journals Oxo-M and 4-PPBP Delivery via Multi-Domain Peptide Hydrogel Toward Tendon Regeneration

2021 ◽  
Author(s):  
Ga Young Park ◽  
Solaiman Tarafder ◽  
Samantha Lewis ◽  
Soomin Park ◽  
Ryunhyung Park ◽  
...  
Keyword(s):  
Small Molecules ◽  
Release Kinetics ◽  
Tendon Healing ◽  
Tendon Regeneration ◽  
Tenogenic Differentiation ◽  
Domain Peptide ◽  
Kinetics Of

AbstractWe have recently identified novel small molecules, Oxo-M and 4-PPBP, which specifically stimulates endogenous tendon stem/progenitor cells (TSCs) leading to potential regenerative healing of fully-transected tendons. Here we investigated an injectable, multi-domain peptide (MDP) hydrogel providing a controlled delivery of the small molecules for regenerative tendon healing. We investigated the release kinetics of Oxo-M and 4-PPBP from MDP hydrogels and the effect of MDP-released small molecules on tenogenic differentiation of TSCs and in vivo tendon healing. In vitro, MDP showed a sustained release of Oxo-M and 4-PPBP and a slower degradation compared to fibrin. In addition, tenogenic gene expression was significantly increased in TSC with MDP-released Oxo-M and 4-PPBP as compared to the fibrin-released. In vivo, MDP releasing Oxo-M and 4-PPBP significantly improved tendon healing, likely associated with prolonged effects of Oxo-M and 4-PPBP on suppression of M1 macrophages and promotion of M2 macrophages. Comprehensive analyses including histomorphology, digital image processing, and modulus mapping with nanoindentation consistently suggested that Oxo-M and 4-PPBP delivered via MDP further improved tendon healing as compared to fibrin-based delivery. In conclusion, MDP delivered with Oxo-M and 4-PPBP may serve as an efficient regenerative therapeutic for in situ tendon regeneration and healing.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Three-Dimensional Subcellular Organization of Hepatocytes in Intact Liver: Simultaneous Visualization of Cytoskeletal and Membrane Markers by Confocal Microscopy

1996 ◽  
Vol 54 ◽  
pp. 288-289
Author(s):  
Greg V. Martin ◽  
Ann L. Hubbard
Keyword(s):  
Three Dimensional ◽  
Integral Membrane Proteins ◽  
Polarized Secretion ◽  
Microscope Images ◽  
Computer Aided ◽  
Intracellular Organelles ◽  
Cytoskeletal Elements ◽  
Simultaneous Visualization

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.

Regeneration of Bone Defects Using Bioactive Glass Combined with Adipose-derived Mesenchymal Stem Cells. An experimental in vivo study

2019 ◽  
Vol 70 (6) ◽  
pp. 1983-1987
Author(s):  
Cristian Trambitas ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Dorin Constantin Dorobantu ◽  
Flaviu Tabaran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bioactive Glass ◽  
Bone Repair ◽  
Bone Defects ◽  
Calvarial Bone ◽  
Specific Protocol ◽  
Repair Mechanisms ◽  
Male Wistar Rats

Large bone defects are a medical concern as these are often unable to heal spontaneously, based on the host bone repair mechanisms. In their treatment, bone tissue engineering techniques represent a promising approach by providing a guide for osseous regeneration. As bioactive glasses proved to have osteoconductive and osteoinductive properties, the aim of our study was to evaluate by histologic examination, the differences in the healing of critical-sized calvarial bone defects filled with bioactive glass combined with adipose-derived mesenchymal stem cells, compared to negative controls. We used 16 male Wistar rats subjected to a specific protocol based on which 2 calvarial bone defects were created in each animal, one was filled with Bon Alive S53P4 bioactive glass and adipose-derived stem cells and the other one was considered control. At intervals of one week during the following month, the animals were euthanized and the specimens from bone defects were histologically examined and compared. The results showed that this biomaterial was biocompatible and the first signs of osseous healing appeared in the third week. Bone Alive S53P4 bioactive glass could be an excellent bone substitute, reducing the need of bone grafts.

Evaluation of Structure-Controlled Silk Fibroin Coatings for Orthopedic Infection and In-Situ Osteogenesis: In Vitro and In Vivo

2020 ◽  
Author(s):  
Wenhao Zhou ◽  
Teng Zhang ◽  
Jianglong Yan ◽  
QiYao Li ◽  
Panpan Xiong ◽  
...  
Keyword(s):  
Silk Fibroin ◽  
Orthopedic Infection
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