Injectable and Gellable Chitosan Formulations Filled with Cellulose Nanofibers for Intervertebral Disc Tissue Engineering

The development of non-cellularized injectable suspensions of viscous chitosan (CHI) solutions (1.7–3.3% (w/w)), filled with cellulose nanofibers (CNF) (0.02–0.6% (w/w)) of the type nanofibrillated cellulose, was proposed for viscosupplementation of the intervertebral disc nucleus pulposus tissue. The achievement of CNF/CHI formulations which can gel in situ at the disc injection site constitutes a minimally-invasive approach to restore damaged/degenerated discs. We studied physico-chemical aspects of the sol and gel states of the CNF/CHI formulations, including the rheological behavior in relation to injectability (sol state) and fiber mechanical reinforcement (gel state). CNF-CHI interactions could be evidenced by a double flow behavior due to the relaxation of the CHI polymer chains and those interacting with the CNFs. At high shear rates resembling the injection conditions with needles commonly used in surgical treatments, both the reference CHI viscous solutions and those filled with CNFs exhibited similar rheological behavior. The neutralization of the flowing and weakly acidic CNF/CHI suspensions yielded composite hydrogels in which the nanofibers reinforced the CHI matrix. We performed evaluations in relation to the biomedical application, such as the effect of the intradiscal injection of the CNF/CHI formulation in pig and rabbit spine models on disc biomechanics. We showed that the injectable formulations became hydrogels in situ after intradiscal gelation, due to CHI neutralization occurring in contact with the body fluids. No leakage of the injectate through the injection canal was observed and the gelled formulation restored the disc height and loss of mechanical properties, which is commonly related to disc degeneration.

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Cellulose Nanofiber-Reinforced Chitosan Hydrogel Composites for Intervertebral Disc Tissue Repair

Biomimetics ◽

10.3390/biomimetics4010019 ◽

2019 ◽

Vol 4 (1) ◽

pp. 19 ◽

Cited By ~ 15

Author(s):

Ingo Doench ◽

Tuan Tran ◽

Laurent David ◽

Alexandra Montembault ◽

Eric Viguier ◽

...

Keyword(s):

Intervertebral Disc ◽

Ex Vivo ◽

Cellulose Nanofibers ◽

Nanofibrillated Cellulose ◽

Biological Properties ◽

Cellulose Nanofiber ◽

Disc Tissue ◽

Microtensile Testing ◽

Hydrogel Composites ◽

Chitosan Hydrogels

The development of non-cellularized composites of chitosan (CHI) hydrogels, filled with cellulose nanofibers (CNFs) of the type nanofibrillated cellulose, was proposed for the repair and regeneration of the intervertebral disc (IVD) annulus fibrosus (AF) tissue. With the achievement of CNF-filled CHI hydrogels, biomaterial-based implants were designed to restore damaged/degenerated discs. The structural, mechanical and biological properties of the developed hydrogel composites were investigated. The neutralization of weakly acidic aqueous CNF/CHI viscous suspensions in NaOH yielded composites of physical hydrogels in which the cellulose nanofibers reinforced the CHI matrix, as investigated by means of microtensile testing under controlled humidity. We assessed the suitability of the achieved biomaterials for intervertebral disc tissue engineering in ex vivo experiments using spine pig models. Cellulose nanofiber-filled chitosan hydrogels can be used as implants in AF tissue defects to restore IVD biomechanics and constitute contention patches against disc nucleus protrusion while serving as support for IVD regeneration.

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Scaffolds for Drug Delivery in Tissue Engineering

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2008.1.2.1 ◽

2008 ◽

Vol 1 (2) ◽

pp. 113-123 ◽

Cited By ~ 2

Author(s):

Vikas V. Gaikwad ◽

Abasaheb B. Patil ◽

Madhuri V. Gaikwad

Keyword(s):

Drug Delivery ◽

Tissue Engineering ◽

Heart Diseases ◽

Cartilage Regeneration ◽

Tissue Growth ◽

The Body ◽

Patient Specific ◽

In Situ Gel ◽

Heart Muscle Cells

Scaffolds are used for drug delivery in tissue engineering as this system is a highly porous structure to allow tissue growth. Although several tissues in the body can regenerate, other tissue such as heart muscles and nerves lack regeneration in adults. However, these can be regenerated by supplying the cells generated using tissue engineering from outside. For instance, in many heart diseases, there is need for heart valve transplantation and unfortunately, within 10 years of initial valve replacement, 50–60% of patients will experience prosthesis associated problems requiring reoperation. This could be avoided by transplantation of heart muscle cells that can regenerate. Delivery of these cells to the respective tissues is not an easy task and this could be done with the help of scaffolds. In situ gel forming scaffolds can also be used for the bone and cartilage regeneration. They can be injected anywhere and can take the shape of a tissue defect, avoiding the need for patient specific scaffold prefabrication and they also have other advantages. Scaffolds are prepared by biodegradable material that result in minimal immune and inflammatory response. Some of the very important issues regarding scaffolds as drug delivery systems is reviewed in this article.

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Ferromagnetic soft catheter robots for minimally invasive bioprinting

Nature Communications ◽

10.1038/s41467-021-25386-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Cheng Zhou ◽

Youzhou Yang ◽

Jiaxin Wang ◽

Qingyang Wu ◽

Zhuozhi Gu ◽

...

Keyword(s):

Minimally Invasive ◽

The Body ◽

Magnetic Actuation ◽

Internal Organs ◽

Planar Surfaces ◽

Reinforced Polymer ◽

Direct Fabrication ◽

Digitally Controlled

AbstractIn vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

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Influence of biological origin on the tensile properties of cellulose nanopapers

Cellulose ◽

10.1007/s10570-021-03935-2 ◽

2021 ◽

Author(s):

Katri S. Kontturi ◽

Koon-Yang Lee ◽

Mitchell P. Jones ◽

William W. Sampson ◽

Alexander Bismarck ◽

...

Keyword(s):

Tensile Strength ◽

Cell Wall ◽

Bacterial Cellulose ◽

Raw Materials ◽

Cellulose Nanofibers ◽

Nanofibrillated Cellulose ◽

Primary Cell Wall ◽

Biological Origin ◽

Basic Principles ◽

Fiber Mats

Abstract Cellulose nanopapers provide diverse, strong and lightweight templates prepared entirely from sustainable raw materials, cellulose nanofibers (CNFs). Yet the strength of CNFs has not been fully capitalized in the resulting nanopapers and the relative influence of CNF strength, their bonding, and biological origin to nanopaper strength are unknown. Here, we show that basic principles from paper physics can be applied to CNF nanopapers to illuminate those relationships. Importantly, it appeared that ~ 200 MPa was the theoretical maximum for nanopapers with random fibril orientation. Furthermore, we demonstrate the contrast in tensile strength for nanopapers prepared from bacterial cellulose (BC) and wood-based nanofibrillated cellulose (NFC). Endemic amorphous polysaccharides (hemicelluloses) in NFC act as matrix in NFC nanopapers, strengthening the bonding between CNFs just like it improves the bonding between CNFs in the primary cell wall of plants. The conclusions apply to all composites containing non-woven fiber mats as reinforcement. Graphic abstract

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Interfacial improvements in cellulose nanofibers reinforced polylactide bionanocomposites prepared by in situ reactive extrusion

Polymers for Advanced Technologies ◽

10.1002/pat.5264 ◽

2021 ◽

Author(s):

Feng‐Jiao Li ◽

Xi‐Tong Yu ◽

Zan Huang ◽

Ding‐Fu Liu

Keyword(s):

Cellulose Nanofibers ◽

Reactive Extrusion

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Shear-Induced and Nanofiber-Nucleated Crystallization of Novel Aliphatic–Aromatic Copolyesters Delineated for In Situ Generation of Biodegradable Nanocomposites

Polymers ◽

10.3390/polym13142315 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2315

Author(s):

Ramin Hosseinnezhad

Keyword(s):

Shear Rate ◽

Cooling Rate ◽

Isothermal Crystallization ◽

Cellulose Nanofibers ◽

Crystallization Time ◽

Nucleation Density ◽

Shear Rates ◽

Biodegradable Nanocomposites ◽

In Situ Generation

The shear-induced and cellulose-nanofiber nucleated crystallization of two novel aliphatic–aromatic copolyesters is outlined due to its significance for the in situ generation of biodegradable nanocomposites, which require the crystallization of nanofibrous sheared inclusions at higher temperatures. The shear-induced non-isothermal crystallization of two copolyesters, namely, poly(butylene adipate-co-succinate-co-glutarate-co-terephthalate) (PBASGT) and poly(butylene adipate-co-terephthalate) (PBAT), was studied following a light depolarization technique. To have a deep insight into the process, the effects of the shear rate, shear time, shearing temperature and cooling rate on the initiation, kinetics, growth and termination of crystals were investigated. Films of 60 μm were subjected to various shear rates (100–800 s−1) for different time intervals during cooling. The effects of the shearing time and increasing the shear rate were found to be an elevated crystallization temperature, increased nucleation density, reduced growth size of lamella stacks and decreased crystallization time. Due to the boosted nucleation sites, the nuclei impinged with each other quickly and growth was hindered. The effect of the cooling rate was more significant at lower shear rates. Shearing the samples at lower temperatures, but still above the nominal melting point, further shifted the non-isothermal crystallization to higher temperatures. As a result of cellulose nanofibers’ presence, the crystallization of PBAT, analyzed by DSC, was shifted to higher temperatures.

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Mammary-type Myofibroblastoma with Leiomyomatous Differentiation: A Rare Variant with Potential Pitfalls

International Journal of Surgical Pathology ◽

10.1177/10668969211031309 ◽

2021 ◽

pp. 106689692110313

Author(s):

Alexander M. Strait ◽

Julia A. Bridge ◽

Anthony J. Iafrate ◽

Marilyn M. Li ◽

Feng Xu ◽

...

Keyword(s):

Adipose Tissue ◽

Transcriptome Sequencing ◽

Smooth Muscle Actin ◽

The Body ◽

Muscle Actin ◽

Mature Adipose Tissue ◽

Spindle Cells ◽

Whole Transcriptome Sequencing ◽

Whole Transcriptome

Myofibroblastoma is a rare, benign stromal tumor with a diverse morphologic spectrum. Mammary-type myofibroblastoma (MTMF) is the extra-mammary counterpart of this neoplasm and its occurrence throughout the body has become increasingly recognized. Similar morphologic variations of MTMF have now been described which mirror those seen in the breast. We describe a case of intra-abdominal MTMF composed of short fascicles of eosinophilic spindle cells admixed with mature adipose tissue. The spindle cells stained diffusely positive for CD34, desmin, smooth muscle actin, and h-caldesmon by immunohistochemistry. Concurrent loss of RB1 (13q14) and 13q34 loci were confirmed by fluorescence in situ hybridization whereas anchored multiplex PCR and whole transcriptome sequencing did not reveal any pathognomonic fusions suggesting an alternative diagnosis. To the best of our knowledge this is the first documented case of leiomyomatous variant of MTMF.

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Facile Synthesis and Characterization of Palm CNF-ZnO Nanocomposites with Antibacterial and Reinforcing Properties

International Journal of Molecular Sciences ◽

10.3390/ijms22115781 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5781

Author(s):

Janarthanan Supramaniam ◽

Darren Yi Sern Low ◽

See Kiat Wong ◽

Loh Teng Hern Tan ◽

Bey Fen Leo ◽

...

Keyword(s):

Plant Biomass ◽

Cellulose Nanofibers ◽

High Strength ◽

Salmonella Typhi ◽

Particle Sizes ◽

Mechanical Reinforcement ◽

Uniform Size ◽

Preparation Methods ◽

Potential Applications

Cellulose nanofibers (CNF) isolated from plant biomass have attracted considerable interests in polymer engineering. The limitations associated with CNF-based nanocomposites are often linked to the time-consuming preparation methods and lack of desired surface functionalities. Herein, we demonstrate the feasibility of preparing a multifunctional CNF-zinc oxide (CNF-ZnO) nanocomposite with dual antibacterial and reinforcing properties via a facile and efficient ultrasound route. We characterized and examined the antibacterial and mechanical reinforcement performances of our ultrasonically induced nanocomposite. Based on our electron microscopy analyses, the ZnO deposited onto the nanofibrous network had a flake-like morphology with particle sizes ranging between 21 to 34 nm. pH levels between 8–10 led to the formation of ultrafine ZnO particles with a uniform size distribution. The resultant CNF-ZnO composite showed improved thermal stability compared to pure CNF. The composite showed potent inhibitory activities against Gram-positive (methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative Salmonella typhi (S. typhi) bacteria. A CNF-ZnO-reinforced natural rubber (NR/CNF-ZnO) composite film, which was produced via latex mixing and casting methods, exhibited up to 42% improvement in tensile strength compared with the neat NR. The findings of this study suggest that ultrasonically-synthesized palm CNF-ZnO nanocomposites could find potential applications in the biomedical field and in the development of high strength rubber composites.

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In Situ Generation of Green Hybrid Nanofibrillar Polymer-Polymer Composites—A Novel Approach to the Triple Shape Memory Polymer Formation

Polymers ◽

10.3390/polym13121900 ◽

2021 ◽

Vol 13 (12) ◽

pp. 1900

Author(s):

Ramin Hosseinnezhad ◽

Iurii Vozniak ◽

Fahmi Zaïri

Keyword(s):

Polymer Blends ◽

Shape Memory ◽

Shape Memory Polymer ◽

Cellulose Nanofibers ◽

Polymeric Materials ◽

Novel Approach ◽

Phase Transition Temperatures ◽

Triple Shape Memory

The paper discusses the possibility of using in situ generated hybrid polymer-polymer nanocomposites as polymeric materials with triple shape memory, which, unlike conventional polymer blends with triple shape memory, are characterized by fully separated phase transition temperatures and strongest bonding between the polymer blends phase interfaces which are critical to the shape fixing and recovery. This was demonstrated using the three-component system polylactide/polybutylene adipateterephthalate/cellulose nanofibers (PLA/PBAT/CNFs). The role of in situ generated PBAT nanofibers and CNFs in the formation of efficient physical crosslinks at PLA-PBAT, PLA-CNF and PBAT-CNF interfaces and the effect of CNFs on the PBAT fibrillation and crystallization processes were elucidated. The in situ generated composites showed drastically higher values of strain recovery ratios, strain fixity ratios, faster recovery rate and better mechanical properties compared to the blend.

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