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Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.
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2015 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 12, p. 70-80, article id S1742-7061(14)00486-3Article in journal (Refereed) Published
Abstract [en]

The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes for the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500μm thick RHCIII-MPC constructs comprising over 85% water are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, unlike the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30μm wide fibronectin stripes enhanced cell attachment and showed the highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas.

Place, publisher, year, edition, pages
2015. Vol. 12, p. 70-80, article id S1742-7061(14)00486-3
Keywords [en]
Collagen, Cornea, Hydrogel, Laser profiling, Surface modification
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:uu:diva-364449DOI: 10.1016/j.actbio.2014.10.035PubMedID: 25448347OAI: oai:DiVA.org:uu-364449DiVA, id: diva2:1259204
Available from: 2018-10-29 Created: 2018-10-29 Last updated: 2018-10-29
In thesis
1. Composite Regenerative Scaffolds
Open this publication in new window or tab >>Composite Regenerative Scaffolds
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Regenerative medicine and tissue engineering solutions of heavily innervated tissues are at this point lacklustre. This thesis expands our knowledge of appropriate acellular scaffolds for tissue repair in general and nerve regeneration in particular. The optimal surgical procedure for the implantation of artificial extracellular matrix (ECM) was evaluated for recombinant human collagen (RHCIII) implants. Suturing techniques, as well as the usage of human amniotic membrane “bandages” were evaluated. While complete regeneration of corneal tissues occurred, only slight differences in effects of surgical technique could be found.

The safety and efficacy of clinical trials using mesenchymal stromal cells (MSCs) was evaluated by conducting a systematic review and meta-analysis. MSC therapy was shown to be safe, with no increases mortality, rehospitalization or adverse events. There was also an indication of efficacy, as the overall mortality in the studies included was significantly smaller in the MSC treated group.

Multicomponent hydrogel capsules encapsulating single cells were developed. Capsules manufactured from gelatin, agarose and fibrinogen were compared to pure gelatin capsules. The composite capsules successfully delayed cell release and prolonged cell survival.

Surface patterning of collagen based biomimetic corneas was performed by microcontact printing. The ability of different sizes of fibronectin stripes to stimulate cell adhesion and proliferation was compared. The patterned surfaces improved cell adhesion, as well as proliferation markers.

Conductive polymer composites were manufactured for use as nerve guides. The guides were created from electrospun polycaprolactone fibers coated with a series of different poly(3,4-ethylenedioxythiophene) films. A comparison of nerve progenitor growth and differentiation on the composite fibers was performed. Both the effects of fiber composition and MSC co-culture was investigated, with or without electrostimulation. MSC treatments and polymer coating was both important for nerve cell differentiation and growth.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 37
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1741
Keywords
nerve, neurite, regeneration, PEDOT, PEDOT:Tosylate, electrostimulation
National Category
Biomaterials Science Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-364454 (URN)978-91-513-0496-0 (ISBN)
Public defence
2018-12-17, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2018-11-27 Created: 2018-10-29 Last updated: 2018-12-27

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