uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Self-healing Hybrid Nanocomposites consisting of Bisphosphonated Hyaluronan and Calcium Phosphate Nanoparticles
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
Show others and affiliations
2014 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 25, 6918-6929 p.Article in journal (Refereed) Published
Abstract [en]

Non-covalent interactions are often regarded as insufficient to construct macroscopic materials of substantial integrity and cohesion. However, the low binding energy of such reversible interactions can be compensated by increasing their number to work in concert to create strong materials. Here we present the successful development of an injectable, cohesive nanocomposite hydrogel based on reversible bonds between calcium phosphate nanoparticles and bisphosphonate-functionalized hyaluronic acid. These nanocomposites display a capacity for self-healing as well as adhesiveness to mineral surfaces such as enamel and hydroxyapatite. Most importantly, these non-covalently cross-linked composites are surprisingly robust yet biodegradable upon extensive in vitro and in vivo testing and show bone interactive capacity evidenced by bone ingrowth into material remnants. The herein presented method provides a new methodology for constructing nanoscale composites for biomedical applications, which owe their integrity to reversible bonds.

Place, publisher, year, edition, pages
2014. Vol. 35, no 25, 6918-6929 p.
National Category
Materials Chemistry Polymer Chemistry
URN: urn:nbn:se:uu:diva-224369DOI: 10.1016/j.biomaterials.2014.05.003ISI: 000338386800024OAI: oai:DiVA.org:uu-224369DiVA: diva2:716459
Available from: 2014-05-09 Created: 2014-05-09 Last updated: 2014-08-12Bibliographically approved
In thesis
1. Multi-functional Hyaluronan Based Biomaterials for Biomedical Applications
Open this publication in new window or tab >>Multi-functional Hyaluronan Based Biomaterials for Biomedical Applications
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis presents strategies for constructing multi-functional biomaterials based on hyaluronan (HA) derivatives for various biomedical applications, such as drug delivery, tissue regeneration, and imaging biomaterials. The aim of this study is to improve the functionalities of HA biomaterials as well as simplify the preparation procedures.  Native HA polymer contains D-glucuronic acid residue with a carboxyl group per disaccharide unit that can be easily modified by carbodiimide-mediated amidation reaction. Therefore, we have designed a series of orthogonal groups (hydrazide, carbazate, aldehyde, and thiol) that can be linked to HA under mild conditions using the carbodiimide chemistry. Multiple functionalities can be introduced to the obtained HA derivatives via chemoselective “click”-type transformations.  

The modified HA derivatives were used for the preparation of either nanogel particles (NPs) or bulk hydrogels. Due to “click” character of the reactions used, structural HA transformations were performed with high fidelity on different scales including molecular (polymers), nanometer (NPs), and a visible scale (bulk hydrogels). By linking pyrene or camptothecin to hydrophilic HA backbone, amphiphilic polymers were obtained and utilized as drug delivery carriers or prodrugs, respectively. Subsequently, physically loaded drug (doxorubicin) could be released upon degradation of HA carriers, while the chemically linked camptothecin was released intact by a thiol-triggered cleavage reaction. Bisphosphonated HA (HA-BP) polymers were prepared to induce hydrogel scaffold bio-mineralization for bone regeneration application. Moreover, we could recruit strong binding capacity of bisphosphonate (BP) groups to calcium ions for the formation of physically crosslinked HA-BP gel upon simple mixing of the polymer and calcium phosphate nanoparticle components. This gel was more stable in vivo compared to hydrazone crosslinked HA gels. Furthermore, the hydrogel composed of fluorine-19 (19F) linked HA polymer was successfully observed by both 1H and 19F MR imaging.        

In conclusion, the presented herein study describes new approaches for building up multi-functional biomaterials from the HA-based blocks. The utilization of carbodiimide and click chemistries along with the enzymatic degradation of HA allowed simple and efficient interconversion between HA macromolecules, nanoparticles and macroscopic hydrogels. These HA-based biomaterials show high potential for use in the fields of drug delivery, bone regeneration, and imaging techniques.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 51 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1155
hyaluronan, biomaterials functionalizations, biomedical applications, orthogonal chemistry, drug delivery, tissue regeneration, MRI
National Category
Polymer Chemistry Materials Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
urn:nbn:se:uu:diva-224371 (URN)978-91-554-8974-8 (ISBN)
Public defence
2014-09-17, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:00 (English)
Available from: 2014-06-04 Created: 2014-05-09 Last updated: 2014-06-30

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Yang, XiaHilborn, JönsOssipov, Dmitri
By organisation
Polymer Chemistry
In the same journal
Materials ChemistryPolymer Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 587 hits
ReferencesLink to record
Permanent link

Direct link