New hybrid nanoparticles for enhanced drug accumulation in glioblastoma cells

Glioblastoma is the most frequent and aggressive primary malignant tumor of the central nervous system. The efficacy of antineoplastic drugs that are able to cross the blood-brain barrier is limited mainly by various resistance mechanisms. Hence, local strategies have been developed to improve the therapeutic efficacy. Platinum derivatives and one among them, cisplatin, demonstrated promising results when locally administered into the brain of glioblastoma-bearing rats. A more specific vectorization of the active substance may further promote its accumulation within cancer cells, therefore improving its bioavailability. In this context, biocompatible and biodegradable copolymers that are approved for medical applications can be synthesized without any toxic organic solvents or excipients. Their amphiphilicity, namely the combination of both a hydrophilic and a hydrophobic sequence, is responsible for their spontaneous self-assembly in water. Such a formulation process is simple and flexible. The versatile structure of these drug delivery systems allows imaging moieties to be grafted onto their surface while encapsulating a drug within their core. The diagnosis of glioblastoma relies on magnetic resonance imaging (MRI) after the injection of gadolinium-based contrast agents. Thus, the injection of hybrid nanoplatforms that combine an MRI contrast agent and a drug would enable to non-invasively monitor the biodistribution of the treatment by analyzing the tumor response in real time. Personalized medicine and theranostic applications require similar strategies for the purposes of adjusting the treatment regimen to the patient response.

 

 

Such smart drug delivery systems were designed by Lajous and coworkers based on amphiphilic block copolymers. Gadolinium complexes were grafted at the end of the hydrophilic chain while a chemical modification of the other block allowed for cisplatin cross-linking with the copolymer backbone. The self-assembly of these functionalized copolymers in water resulted in stable cisplatin cross-linked nanoparticles with a mean size of 100.63 ± 12.04 nm consistent with biological investigations. High field MRI confirmed the intrinsic potential of these hybrid nanoparticles as alternative MRI contrast agents compared to conventional low molar mass Gd-DTPA complexes. Their infusion within the striatum of glioblastoma-bearing mice resulted in a signal that persisted over time. The accumulation of platinum compounds in human glioblastoma cells when treated with these drug delivery systems and the subsequent formation of Pt-DNA adducts was significantly increased in comparison with free cisplatin by up to 50-fold and 32-fold respectively. These results support the potential of this innovative bimodal tool for further applications.

Hybrid Gd3+/cisplatin cross-linked polymer nanoparticles enhance platinum accumulation and formation of DNA adducts in glioblastoma cell lines  Biomater. Sci., 2018, 6, 2386-2409

 

Read the full article now for free until 11 October

 

About the web writer

Dr. Sudip MukherjeeDr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~35 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an Associate Member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like ChemComm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology, Biofabrication etc.

 

 

 

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Chemically modified nanogels for superior bioavailability

The pharmacokinetics and pharmacodynamics of any drug or nanoparticles plays an important role towards the therapeutic activity, half-life of the therapeutic agent and frequency of dosing of the biomaterial in various diseases. Recently, the development of biopolymer nanogels has received tremendous attention due to their effective delivery of therapeutics, size uniformity, high drug encapsulation capacity, easy preparation, high biocompatibility and size tunability. However, the tendency of these nanogels to disassemble in the bloodstream is cause for concern, due to the interactions with serum proteins and excessive dilution volume that decreases the tumor targeting efficiency through EPR effects. In this regard, substantial research is needed to develop novel platform technologies for bioactive nanogels with enhanced bioavailability.

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In this work, Auzély-Velty and co-workers, developed a novel and easy method to synthesize stable self-assembled hyaluronic acid (HA) nanogels, modified with a thermoresponsive ketone-functional copolymer by hydrazone formation. The cross-linking density played a crucial role in the nanogel stability and pharmacokinetics, and it was easily tuned by varying dihydrazide crosslinker to ketone ratio. Several physicochemical characterizations including cryo-transmission, dynamic light scattering and scanning electron microscopy were performed to analyze the size, morphology and stability of the nanogels. The authors showed the in vitro cellular uptake of the nanogels by CD44 receptor mediated pathway further confirmed the effectiveness of the cross-linking strategy. The modified nanogels demonstrated superior bioavailability in tumors, with enhanced blood circulation for over 24 hours, demonstrated in vivo in biodistribution studies with mouse tumor models. Overall, these nanogels are inexpensive, stable, easily tunable and biocompatible, thus holding promise for the discovery of a new class of molecules for cancer therapy application in near future.

 

This article is free to read and download until 13th August.

A versatile method for the selective core-crosslinking of hyaluronic acid nanogels via ketone-hydrazide chemistry: from chemical characterization to in vivo biodistribution Biomater. Sci., 2018, 6, 1754-1763

 

About the web writer

Dr. Sudip MukherjeeDr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~35 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like ChemComm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology, Biofabrication etc.

Contact Email: sudip.mukherjee@rice.edu
Twitter: https://twitter.com/sudip_88

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2018 Biomaterials Science Lectureship

It is with great pleasure that we announce Prof. Zhen Gu (University of North Carolina at Chapel Hill and North Carolina State University) as the recipient of the 2018 Biomaterials Science Lectureship!

Professor Zhen GuThe Biomaterials Science Lectureship is an annual award that honours an early-career researcher for their significant contribution to the biomaterials field. The recipient is selected by the Biomaterials Science Editorial Board from a list of candidates nominated by the community.

This year we are delighted to award the Lectureship to Professor Zhen Gu (University of North Carolina at Chapel Hill and North Carolina State University). He will present the Biomaterials Science lecture and receive his award at the European Society for Biomaterials Annual Meeting in Maastricht in September 2018.

Prof. Zhen Gu received his B.S. degree in Chemistry and M.S. degree in Polymer Chemistry and Physics from Nanjing University. In 2010, he obtained Ph.D. at the University of California, Los Angeles, under the guidance of Prof. Yi Tang in the Department of Chemical and Biomolecular Engineering. He was a Postdoctoral Associate working with Profs. Robert Langer and Daniel Anderson at MIT and Harvard Medical School during 2010 to 2012.

Prof. Zhen Gu is the recipient of the Young Investigator Award of the Controlled Release Society (CRS, 2017), Sloan Research Fellowship (2016), Pathway Award of the American Diabetes Association (ADA, 2015) and Young Innovator Award in Cellular and Molecular Engineering of the Biomedical Engineering Society (BMES, 2015). MIT Technology Review listed him in 2015 as one of the global top innovators under the age of 35 (TR35).

His group studies controlled drug delivery, bio-inspired materials and nanobiotechnology, especially for cancer and diabetes treatment.

To learn more about Zhen’s research, have a look at his recent publications in Biomaterials Science and our sister journals:

Engineering DNA scaffolds for delivery of anticancer therapeutics
Wujin Sun  and  Zhen Gu
Biomater. Sci., 2015,3, 1018-1024, Minireview

Advances in liquid metals for biomedical applications
Junjie Yan,  Yue Lu,  Guojun Chen,  Min Yang  and  Zhen Gu
Chem. Soc. Rev., 2018,47, 2518-2533, Tutorial Review

Investigation and intervention of autophagy to guide cancer treatment with nanogels
Xudong Zhang,  Xin Liang,  Jianjun Gu,  Danfeng Chang,b  Jinxie Zhang,  Zhaowei Chen,  Yanqi Ye,  Chao Wang,  Wei Tao,  Xiaowei Zeng,  Gan Liu,  Yongjun Zhang,  Lin Mei  and  Zhen Gu
Nanoscale, 2017,9, 150-163, Paper

Internalized compartments encapsulated nanogels for targeted drug delivery
Jicheng Yu,  Yuqi Zhang,  Wujin Sun,  Chao Wang,  Davis Ranson,  Yanqi Ye,  Yuyan Weng  and  Zhen Gu
Nanoscale, 2016,8, 9178-9184, Paper

Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery
Yue Lu,  Ran Mo,  Wanyi Tai,  Wujin Sun,  Dennis B. Pacardo,  Chenggen Qian,  Qundong Shen,  Frances S. Ligler  and  Zhen Gu
Chem. Commun., 2014,50, 15105-15108, Communication

Please join us in congratulating Zhen on his award!

 

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Cancer theranostics applications of Graphene Oxides

Graphene oxide (GO) has actively been used in various biomedical applications, including biomedical sensors, electronic sensors, functional composites and so on. In addition to having a large surface area, large-scale manufacturability and being dispersible in water, GO shows strong fluorescence and conjugation properties, owing to the abundance of oxygen functional groups on its surface.

Numerous methods have been developed to enable photon emission from GO sheets, such as reduction, labeling with fluorescent protein, and cleaving GO sheets into smaller fragments to produce graphene quantum dots (QDs), although this method does remove oxygen from the carbon lattice. This is a problem because reducing the oxygen content prevents the further functionalization of GO structures with biomolecules. Furthermore, such methods have been reported to cause cytotoxicity.

Cancer theranostics applications of Graphene Oxides

In this work by the Chen and co-workers, a blue fluorescence was induced in a GO suspension by triggering a phase transformation in GO through treatment with a simple, one-step mild annealing. Previously, it had been difficult to facilitate light emission from GO while preserving the oxygen content and maintaining low cytotoxicity. However, this work suggests that by providing a nano-bio interface for reactions with biomolecules the physical difficulties can be overcome. In this case, GO acts as a bio-imaging agent as well as a functionalization platform for biomolecules. Material characterization and biocompatibility tests were performed to examine the purity, inherent property and non-toxicity of the system. The mechanism for enhanced blue fluorescence upon mild annealing was discovered and modeled through atomistic simulations. Most importantly, GO shows an appealing capability in drug delivery and cellular imaging simultaneously. Overall, this method is expected to be inexpensive, rapid and straightforward, thus holding promise for the development of a whole new class of GO-based nanomaterials for cancer theranostics application in near future.

 

This article is free to read until 30 May

 

Simultaneous drug delivery and cellular imaging using graphene oxide Biomater. Sci., 2018, 6, 813-819

 

About the webwriter

Dr. Sudip MukherjeeDr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like Chem Comm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc.

Contact Email: sudip.mukherjee@rice.edu

Twitter: https://twitter.com/sudip_88

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Focus on: Engineering Advanced Biologics

Written by Webwriter Yingfei Xue

Protein-based biologics are gaining tremendous interests in the biomedical field after several successful translations into commercialized products. To this end, key hurdles in the development of protein-based therapeutics need to be properly addressed first. One of the most prominent issues is the instability of protein therapeutics in vivo, which requires higher and more frequent doses. As a result, protein-based therapy can become prohibitive in cost and may pose potential safety risks. Engineering protein therapeutics using biomaterials offer unique strategies to solve this problem by prolonging the half-life and enhancing the efficacy of these. In this blog, we feature three articles published in Biomaterials Science recently on the topic of Engineering Advanced Biologics as therapeutic agents.

 

Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis

 

1. Multivalent conjugates of basic fibroblast growth factor enhance in vitro proliferation and migration of endothelial cells
Aline Zbinden, Shane Browne, Eda I. Altiok, Felicia L. Svedlund, Wesley M. Jackson and Kevin E. Healy
Biomater. Sci., 2018, Advance Article, DOI: 10.1039/C7BM01052D

The authors reported the chemical conjugation of basic fibroblast growth factor (bFGF) onto hyaluronic acid (HA). Such multivalent conjugates were envisioned to increase residence time in vivo, protect bFGF from enzymatic degradation, and enhance protein bioactivity. Using a small molecule linker (N-(ε-Maleimidocaproic acid) hydrazide), bFGF was successfully conjugated at two different protein-to-polymer ratios and their structures were confirmed by extensive physico-chemical characterization. Compared to bFGF alone, HA conjugated bFGF displayed enhanced activity to promote the proliferation and more interestingly, the scratch closure of human umbilical cord vein endothelial cells. It’s noteworthy that the protein-to-polymer ratio and the conjugate size are two key parameters that could be easily tuned to modulate the bioactivity of the conjugate.

 

2. Synergistic effects of hyaluronate – epidermal growth factor conjugate patch on chronic wound healing
Yun Seop Kim, Dong Kyung Sung, Won Ho Kong, Hyemin Kim and Sei Kwang Hahn
Biomater. Sci., 2018, Advance Article, DOI: 10.1039/C8BM00079D

Similar to the strategy discussed above, the authors also utilized the biocompatible HA as carrier to conjugate epidermal growth factor (EGF) which is otherwise labile in vivo. The enzymatic degradation and stability studies revealed the superior stability of EGF when conjugated with HA. In vitro, HA–EGF conjugate increased keratinocyte proliferation, VEGF secretion, and migration towards scratch closure when compared to EGF alone. In vivo, HA–EGF conjugates loaded HA patch closed the wound in a rat model by enhancing de novo ECM secretion and mitigating inflammatory response. Overall, those comprehensive studies demonstrated the significance of protein-HA conjugates in improving the therapeutic effects of protein biologics.

 

3. Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis
Liane E. Tellier, Elda A. Treviño, Alexandra L. Brimeyer, David S. Reece, Nick J. Willett, Robert E. Guldbergde and Johnna S. Temenoff
Biomater. Sci., 2018, Advance Article, DOI: 10.1039/C8BM00010G

Here, the authors aimed to improve the delivery of TNF-α-stimulated gene-6 (TSG-6) for treating osteoarthritis. Specifically, they focused on heparin, another glycosaminoglycan, as a carrier biomaterial for TSG-6 delivery. It was first discovered that N-desulfated heparin maintained the beneficial role in promoting the bioactivity of TSG-6. Microparticles were thus made from N-desulfated heparin followed by TSG-6 encapsulation. TSG-6 was able to be released and demonstrated significantly higher anti-plasmin activity compared to soluble TSG-6. In a rat medial meniscal transection model, treatment of TSG-6 delivered by N-desulfated heparin but not in soluble form resulted in similar cartilage thickness, volume and GAG level compared to uninjured cartilage. These results showcased the advantages of heparin based microparticle in preserving and enhancing the bioactivity of therapeutic TSG-6 protein.

 

All articles free to read until 24 May

 

About the webwriter

Yingfei XueYingfei Xue is a web writer for Biomaterials Science. Currently, he is a PhD candidate and graduate student researcher in Dr. Shilpa Sant lab at the University of Pittsburgh, USA. His research focus on nano-/micro-technology in novel heart valve therapy. Find him on Twitter: @Phil_Xue or connect him on ResearchGate

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Outstanding Reviewers for Biomaterials Science in 2017

We would like to highlight the Outstanding Reviewers for Biomaterials Science in 2017, as selected by the editorial team, for their significant contribution to the journal. The reviewers have been chosen based on the number, timeliness and quality of the reports completed over the last 12 months.

We would like to say a big thank you to those individuals listed here as well as to all of the reviewers that have supported the journal. Each Outstanding Reviewer will receive a certificate to give recognition for their significant contribution.

Dr Kaimin Cai, University of Illinois at Urbana-Champaign, ORCID: 0000-0001-9442-8312
Dr Qing Cai, Beijing University of Chemical Technology, ORCID: 0000-0001-6618-0321
Dr Jinzhi Du, South China University of Technology, ORCID: 0000-0003-4037-1212
Dr Xiaohu Gao, University of Washington
Dr Xu Han, University of Miami, ORCID: 0000-0001-9095-1755 
Dr Xun He, Texas A&M University, ORCID: 0000-0002-4002-7932
Dr Zheng-Hong Peng, Yale University, ORCID: 0000-0001-9783-5108  
Dr Wujin Sun, University of North Carolina at Chapel Hill, ORCID: 0000-0002-3167-111X
Dr Wentao Wang, Florida State University, ORCID: 0000-0003-2273-4171
Dr Yazhen Zhu, University of California, Los Angeles ORCID: 0000-0002-2130-8085

We would also like to thank the Biomaterials Science board and the biomaterials research community for their continued support of the journal, as authors, reviewers and readers.

If you would like to become a reviewer for our journal, just email us with details of your research interests and an up-to-date CV or résumé.  You can find more details in our author and reviewer resource centre

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On-demand chemotherapy using photo-activated micelles

Preventing or minimizing the adverse effects of anti-cancer chemotherapy has been a great challenge, due to the non-specific distribution of chemodrugs in healthy organs. Many previous works have attempted to address this issue by improving the accumulation of cytotoxic drugs in the tumor, with various targeting strategies. All the drug targeting methods enhance efficacy and reduce side-effects to a certain extent, but they cannot completely avoid the unfavourable adverse effects. Site-specific activation of chemotherapeutic drugs via a photo trigger has been a promising means of reducing side-effects.

On-demand chemotherapy using photo-activated micelles

 

The Zhao group at Tianjin University report the use of cyclodextrin-bearing polymer micelles for the on-demand delivery of a photoswitchable microtubule inhibitor, to achieve precision chemotherapy. The tailored inhibitor displays conformation-dependent cytotoxicity with a low potency; the “trans” isomer is thermodynamically stable and inactive, whereas the “cis” isomer is active, but thermodynamically unstable. Light irradiation activates the drug from the “trans” to “cis” form, which then instantly induces rapid drug release. Such simultaneous drug activation and release could compromise the low drug potency to a certain extent, showing improved anti-cancer efficacy in vitro and in vivo. Therefore, photo-triggered nanosystems could open new avenues of on-demand precision chemotherapy, without the risk of adverse effects on healthy organs and tissues.

This article is free to read until 30 April 18

Photo-triggered micelles: simultaneous activation and release of microtubule inhibitors for on-demand chemotherapy Biomater. Sci., 2018, 6, 511-518

 

About the Web/Blog writer:

Dr. Sudip MukherjeeDr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like ChemComm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc.

Contact Email: sudip.mukherjee@rice.edu

Twitter: https://twitter.com/sudip_88

 

 

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3D Multiscale Fiber Matrices for Bioartificial Livers

The liver is the largest internal organ and gland in the human body and it performs numerous vital functions including metabolism regulation, synthesis, detoxification, excretion, and body homeostasis. Many factors, such as viral hepatitis, drugs, toxins, or cardiac-related hepatic ischemia, can cause liver failure. According to the World Health Organisation (WHO) around 10% of the world’s population is suffering from chronic liver disease. The eventual treatment for chronic liver diseases is liver transplantation; however, an inadequate supply of donors is a major limitation for this therapy. With the large number of patients awaiting a liver transplant, there is urgent need for the development of a temporary liver support system, which could be used until a transplant liver is available, or until the patient’s own liver regains its function. Temporary liver supports can be artificial or bioartificial. Artificial support devices are used for detoxification only, whereas bioartificial support devices are more promising, and have biomaterial and cellular components, allowing for both detoxification and synthetic functions. The aim of this study is to prepare a hollow fiber membrane (HFM) based three-dimension matrix, which is the most crucial part of bioartificial livers, and acts as cell growth promoting material. The microenvironment of the three-dimensional matrix influences the cellular behavior and function, exhibiting proliferation, metabolism and interaction of cells with each other and their environment.

3D multiscale fiber matrices

In this study, the authors developed a three-dimensional liver cell (HepG2) compatible bio-matrix which supports the liver cells, allowing them to grow and multiply robustly. The outer surface of indigenously prepared HFM was modified and made accommodating for the growth of the liver cells. Nanofibers of biocompatible compounds including polycaprolactone, chitosan, and gelatin, which mimic the native cell attachment surface, were deposited on the HFMs. The developed material exhibited excellent hemocompatibility with human blood. Minimal induction of inflammatory response and negligible cytotoxicity was observed. Further evaluation of the liver cell functional activity showed that cells exhibited the key characterstics of typical liver cells by secreting urea and albumin in the medium. The specific activity of cytochrome P450 2C9 (detoxifying enzyme) was found to have increased by 2.78-fold. Hence, these results significantly indicate that the three-dimensional fiber matrix developed in this study open up the possibility to use it for the various applications including (1) a membrane material for bio-artificial liver development, (2) cell metabolic studies and (3) drug testing bioreactor.

Three-dimensional multiscale fiber matrices: development and characterization for increased HepG2 functional maintenance for bio-artificial liver application Biomater. Sci., 2018,6, 280-291.

This article is free to read until the 16 April 2018

 

About the Web/Blog writer:

Dr. Sudip Mukherjee Dr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of The Royal Society of Chemistry, UK. He serves as reviewer for several international journals like Chem Comm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc.

Contact Email: sudip.mukherjee@rice.edu
Twitter: https://twitter.com/sudip_88

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Focus on: Engineered Hydrogels

Written by web writer Yingfei Xue

Hydrogels represent one of the most important classes of biomaterials and have been widely used for drug/cell delivery, tissue engineering, and disease models due to their biocompatibility and biodegradability properties. Traditional bulk hydrogels often suffer from drawbacks such as limited injectability, lack of control over morphology, and low cell adherence. Therefore, hydrogels engineered via innovative biomaterial chemistry and biofabrication technologies aim to overcome these obstacles and hold the promise to translate hydrogel based therapy into clinical setting.

neural stem cells (NSCs) in cell therapy

This month we focus on three articles published in Biomaterials Science reporting the recent advances in engineered hydrogels as therapeutics, 3D printing platforms, and cell culture systems.

 

1. Protein-engineered hydrogels enhance the survival of induced pluripotent stem cell-derived endothelial cells for treatment of peripheral arterial disease
Abbygail A. Foster, Ruby E. Dewi, Lei Cai, Luqia Hou, Zachary Strassberg, Cynthia A. Alcazar, Sarah C. Heilshorn and Ngan F. Huang
Biomater. Sci., 2018, Advance Article
DOI: 10.1039/C7BM00883J

Cell therapies via direct cell transplantation often resulted in limited therapeutic effects due to low cell viability and retention. Therefore, the authors utilized the platform technology of injectable shear-thinning hydrogel (termed as SHIELD) to mitigate such problems. SHIELD consists of engineered recombinant protein and polyethylene glycol modified proline-rich peptide domains, and it promoted cell-matrix interaction to improve cell viability and retention. Additionally, SHIELD was further strengthened by thermoresponsive poly(N-isopropylacrylamide). The encapsulation of human induced pluripotent stem cell-derived endothelial cells in SHIELD protected cells from membrane damage caused by injection and augmented cell proliferation under hypoxia. In a rodent model of peripheral arterial disease, cell injection with SHIELD had significantly higher cell retention in vivo and further promoted microvessel formation to relieve ischemic insult when compared to saline control.

2. Applying macromolecular crowding to 3D bioprinting: fabrication of 3D hierarchical porous collagen-based hydrogel constructs
Wei Long Ng, Min Hao Goh, Wai Yee Yeong, May Win Naing
Biomater. Sci., 2018, Advance Article
DOI: 10.1039/C7BM01015J

It has been well recognized that scaffold architecture plays a critical role in determining the cellular behavior. Tradition hydrogels fabricated by freeze drying, solvent casting, and phase separation were often confined to less controllable architectures. Utilizing 3D bioprinting via drop-on-demand (DOD) technique, the authors printed 3D hierarchical porous collagen scaffolds with finely controlled  pore size and porosity . In this process, droplets of polyvinylpyrrolidone (PVP) were uniformly printed to facilitate the rapid and homogeneous cross-linking, enhance collagen fibrillogenesis, and tune the collagen architecture in a controlled manner. This printing strategy yielded a cytocompatible construct as demonstrated by a primary human dermal fibroblasts model.

3. Evaluation of RGD functionalization in hybrid hydrogels as 3D neural stem cell culture systems
Emanuele Mauri, Alessandro Sacchetti, Nunzio Vicario, Luca Peruzzotti-Jametti, Filippo Rossi and Stefano Pluchino
Biomater. Sci., 2018, Advance Article
DOI: 10.1039/C7BM01056G

To improve the stem cell based therapy for the repair and regeneration of central nervous system, the authors engineered hydrogels which composed of polyethylene glycol, agarose, and polyacrylic acid with cell-adhesive and cell-recognition Arg-Gly-Asp (RGD) motif. When interfacing with neural stem cells, the RGD modified hydrogels enabled a higher ratio of active proliferating cell population compared to a 2D laminin surface or non-RGD hydrogel throughout the 21 day in vitro culture. Additionally, the examination of conditioned media obtained from the in vitro culture revealed the higher level of nutrients contained in the RGD modified hydrogels group, indicating the superior biocompatibility of RGD modified hydrogel construct.

Read these articles for free until 19 March

 

About the webwriter

Yingfei XueYingfei Xue is a web writer for Biomaterials Science. Currently, he is a PhD candidate and graduate student researcher in Dr. Shilpa Sant lab at the University of Pittsburgh, USA.  His research focus on nano-/micro-technology in novel heart valve therapy. Find him on Twitter: @Phil_Xue  or connect with him on ResearchGate.

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Bio-mimicking melanin-manganese nanoparticles for tumor targeting MRI agent

Good quality MRI contrast agents require profound tumor-targeting ability, well relaxivity, along with rapid clearance properties. In this context, endogenous biological mimicking biomaterials, with high biodegradability and biocompatibility hold enormous potential for the development of clinically translatable nanotheranostics platforms. Manganese plays a crucial role in mitochondrial and cellular function and recently, manganese (Mn)-based contrast agents have been receiving significant attention, due to improved biosafety and superior contrast abilities. However, the long term toxicity and non-biodegradability of these inorganic nanoplatforms have significantly halted their clinical progress. In contrast to this, melanin, an asymmetrical natural biopolymer, has garnered enormous attention due to good biocompatibility, biodegradability and MRI contrast imaging abilities. Hence, exploring endogenous natural materials with high contrast properties seems promising as clinically translatable in vivo MRI imaging contrast agent.

melanin-manganese nanoparticles for tumor targeting MRI agent

The Wang group developed an ultra small and water soluble Mn2+ chelating pegylated melanin nanoparticles (MNP-PEG-Mn) demonstrating excellent tumor-targeting Magnetic Resonance Imaging (MRI) ability. The MNP-PEG-Mn nanoparticles show a size of 5.6 nm displaying high chelating stability and low cytotoxicity. Interestingly, the MNP-PEG-Mn nanoparticles show improved longitudinal relaxivity compared to clinically approved MRI contrast agent Gadodiamide. In vivo studies further showcased excellent tumor targeting abilities upon intravenous administration of MNP-PEG-Mn nanoparticles in mouse model. The author further showed that the MNP-PEG-Mn nanoparticles could be excreted via hepatobiliary and renal routes. In this process negligible toxicity was generated to body tissues that indicate high biocompatibility. Altogether, these results clinically validate the tumor targeted T1 MRI contrast properties of bio-mimicking melanin conjugated manganese nanoparticles.

Melanin-manganese nanoparticles with ultrahigh efficient clearance in vivo for tumor-targeting T1 magnetic resonance imaging contrast agent . Biomater. Sci., 2018, 6, 207-215.

This article is free to read until 28 February!

 

About the Web writer:

Dr. Sudip MukherjeeDr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate working at the Department of Bioengineering at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunotherapy, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of The Royal Society of Chemistry, UK. He serves as reviewer for several international journals like Chem Comm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc. He can be contacted by email at sudip.mukherjee@rice.edu or on Twitter.

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