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Smart design of stable hydrazone crosslinked extracellular matrix mimetic hydrogel for tissue engineering application
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
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2012 (Engelska)Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr suppl 1, s. 192-192Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Abstract [en]

Injectable hydrogels are important biomaterials with enormous applications. They are used for various biomedical applications such as diagnostics, 3D cell culture matrix, drug reservoir, encapsulation of bioactive compounds and growth factors, scaffold for tissue engineering etc. We here present our recent development in our efforts to develop hydrogel scaffolds with enhanced rigidity, stability, swelling characteristics. Hydrazone crosslinked gels are attractive due to its simplicity and versatility which could be formed by mixing appropriate aldehyde and hydrazide functionalized hyaluronan. By fine-tuning the electronic character around the hydrazone linkage, we succeeded in developing extremely stable hydrazone bond and utilized it for developing hyaluronan (HA) based synthetic extracellular matrix (ECM) hydrogel. Among the different hydrazides tested, we identified carbonyldihydrazide (CDH) as the best candidate to deliver stable hydrazone linkage. This stability is presumably due to extensive delocalization of the positive charge across neighboring amino groups of CDH. The hydrolytic stability imparted by this group was found to be several folds under acidic, basic and physiological pH when compared to other hydrazones. This tailored hydrogel with CDH also exhibited superior swelling and mechanical properties and enzymatic stability which makes it ideal for tissue engineering application.

Ort, förlag, år, upplaga, sidor
2012. Vol. 6, nr suppl 1, s. 192-192
Nationell ämneskategori
Medicin och hälsovetenskap Polymerkemi
Forskningsämne
Kemi med inriktning mot polymerkemi
Identifikatorer
URN: urn:nbn:se:uu:diva-182412DOI: 10.1002/term.1586ISI: 000308313001311OAI: oai:DiVA.org:uu-182412DiVA, id: diva2:560262
Tillgänglig från: 2012-10-12 Skapad: 2012-10-10 Senast uppdaterad: 2013-02-11Bibliografiskt granskad
Ingår i avhandling
1. Bone Enhancement with BMP-2 for Safe Clinical Translation
Öppna denna publikation i ny flik eller fönster >>Bone Enhancement with BMP-2 for Safe Clinical Translation
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of bone regeneration. However, BMP-2 delivery in a conventional collagen scaffold needs a high dose to achieve an effective outcome. Moreover, such dosage may lead to serious side effects. The aim of the following thesis was to find clinically acceptable strategies reducing the required dose of BMP-2 by improving the delivery and optimizing the preclinical testing of the new approaches. In all the studies hyaluronic acid (HA) hydrogels was used as a carrier for BMP-2.

The HA hydrogel/BMP-2 construct was modified with bioactive matrix components in order to obtain an effective release of BMP-2 and an enhanced bone formation. The most promising were two strategies. In the first one, BMP-2, precomplexed with the glycosaminoglycans dermatan sulfate or heparin prior to loading it into HA hydrogel, protected and prolonged the delivery of the protein, resulting in twofold larger bone formation in comparison to non-complexed BMP-2. In the second strategy, the fibronectin fragment integrin-binding domain (FN) was covalently incorporated into HA hydrogel. The FN remarkably improved the capacity of the material to support the cells attachment and spreading, providing the formation of twice as much bone in comparison to non-functionalized HA hydrogel/BMP-2.

Furthermore, the importance of a proper design of the preclinical study for BMP-2 delivery systems was highlighted. Firstly, proper physicochemical handling of BMP-2 showed the improvement in further in vivo activity.  The use of glass storage vials and an acidic formulation buffer was superior to plastic surfaces and physiological pH. Secondly, while regenerative medicine strategy testing required the use of animal models that matched the research questions related to clinical translation, two new animal models were developed. The subperiosteal mandibular and calvarial models in rats were found to be minimally invasive, convenient and rapid solution for the evaluation of a broad range of approaches including bone augmentation, replacement and regeneration. Both models are primarily relevant for the initial testing of the injectable bone engineering constructs. 

Those clinically translatable approaches presented here could prove to be a powerful platform for a wider use of BMP-2 in orthopedic, plastic surgery and regenerative medicine research.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2013. s. 74
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1009
Nyckelord
Bone repair, Bone healing, Bone morhogenetic protein-2, Osteogenesis, Extracelular matrix, Hyaluronan, Animal model
Nationell ämneskategori
Ortopedi Biomaterialvetenskap
Forskningsämne
Ortopedi; Teknisk fysik med inriktning mot materialvetenskap
Identifikatorer
urn:nbn:se:uu:diva-188027 (URN)978-91-554-8572-6 (ISBN)
Disputation
2013-02-08, Museum Gustavianum - Auditorium Minus, Akademigatan 3, Uppsala, 13:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2013-01-18 Skapad: 2012-12-12 Senast uppdaterad: 2018-01-12Bibliografiskt granskad

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Podiyan, OommenWang, ShujiangKisiel, MartaHilborn, JönsVarghese, Oommen P.

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