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Islam, M. M., Buznyk, O., Reddy, J. C., Pasyechnikova, N., Alarcon, E. I., Hayes, S., . . . Griffith, M. (2018). Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation. NPJ Regenerative medicine, 3, Article ID 2.
Open this publication in new window or tab >>Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation
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2018 (English)In: NPJ Regenerative medicine, ISSN 2057-3995, Vol. 3, article id 2Article in journal (Refereed) Published
Abstract [en]

The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1-2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to near normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal tissue and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients.

National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-152526 (URN)10.1038/s41536-017-0038-8 (DOI)29423280 (PubMedID)
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28
Mak, W. C., Olesen, K., Sivlér, P., Lee, C.-J., Moreno-Jimenez, I., Edin, J., . . . Griffith, M. (2018). Correction: W.C. Mak, et al. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules. J. Funct. Biomater. 2015, 6, 439-453. Journal of Functional Biomaterials, 9(2), Article ID 26.
Open this publication in new window or tab >>Correction: W.C. Mak, et al. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules. J. Funct. Biomater. 2015, 6, 439-453
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2018 (English)In: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 9, no 2, article id 26Article in journal (Other academic) Published
Place, publisher, year, edition, pages
Basel: MDPI, 2018
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-155826 (URN)10.3390/jfb9020026 (DOI)000446652800001 ()29561776 (PubMedID)
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2019-05-04Bibliographically approved
Ong, J. A., Auvinet, E., Forget, K. J., Lagali, N., Fagerholm, P., Griffith, M., . . . Brunette, I. (2016). 3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute. Investigative Ophthalmology and Visual Science, 57(6), 2355-2365
Open this publication in new window or tab >>3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute
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2016 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 6, p. 2355-2365Article in journal (Refereed) Published
Abstract [en]

PURPOSE. The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal diseases. The goal of this phase 1 safety study was to characterize the three-dimensional (3D) corneal shape of the first 10 human patients implanted with a BSS and assess its stability over time. METHODS. Ten patients underwent anterior lamellar keratoplasty using a biosynthetic corneal stromal implant for either advanced keratoconus or central corneal scarring. Surgeries were performed at Linkoping University Hospital, between October and November 2007. Serial corneal topographies were performed on all eyes up to a 4-year follow-up when possible. Three-dimensional shape average maps were constructed for the 10 BSS corneas and for 10 healthy controls. Average 3D shape corneal elevation maps, difference maps, and statistics maps were generated. RESULTS. The biosynthetic stromal substitutes implants remained stably integrated into the host corneas over the 4-year follow-up period, without signs of wound dehiscence or implant extrusion. The biosynthetic stromal substitutes corneas showed steeper surface curvatures and were more irregular than the healthy controls. CONCLUSIONS. Corneal astigmatism and surface steepness were observed 4 years after BSS implantation, while the implants remained stably integrated in the host corneas. Future studies will indicate if biomaterials technology will allow for the optimization of postoperative surface irregularity after anterior stromal replacement, a new window of opportunity that is not available with traditional corneal transplantation techniques.

Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016
Keywords
corneal implants; artificial cornea; corneal topography; corneal transplantation; keratoconus
National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-130307 (URN)10.1167/iovs.15-18271 (DOI)000378041700001 ()27136462 (PubMedID)
Note

Funding Agencies|Canadian Institutes of Health Research, Canada [MOP 106517]; Stem Cell Network, Ottawa, ON, Canada; FRQS Research in Vision Network, Montreal, QC, Canada; County Council of Ostergotland, Sweden; Charles-Albert Poissant Research Chair in Corneal Transplantation, University of Montreal, Canada

Available from: 2016-07-31 Created: 2016-07-28 Last updated: 2018-01-22
Alarcon, E. I., Vulesevic, B., Argawal, A., Ross, A., Bejjani, P., Podrebarac, J., . . . Griffith, M. (2016). Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.. Nanoscale, 8(12), 6484-6489
Open this publication in new window or tab >>Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.
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2016 (English)In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, no 12, p. 6484-6489Article in journal (Refereed) Published
Abstract [en]

Despite the broad anti-microbial and anti-inflammatory properties of silver nanoparticles (AgNPs), their use in bioengineered corneal replacements or bandage contact lenses has been hindered due to their intense yellow coloration. In this communication, we report the development of a new strategy to pre-stabilize and incorporate AgNPs with different colours into collagen matrices for fabrication of corneal implants and lenses, and assessed their in vitro and in vivo activity.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2016
National Category
Biomaterials Science
Identifiers
urn:nbn:se:liu:diva-126612 (URN)10.1039/c6nr01339b (DOI)000372851500033 ()26949000 (PubMedID)
Note

Funding agencies: Natural Sciences and Engineering Research Council [342107, RGPIN-2015-06325]; Swedish Research Council [521-2012-5706, 621-2012-4286]; University of Ottawa; Alexander Graham Bell/Canada Graduate (CGS-M/NSERC) Scholarship; Ontario Graduate Scholarships (OG

Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2017-11-30Bibliographically approved
Ghani, M., Mak, W. C., Cheung, K. Y., Montazer, M., Rezaei, B. & Griffith, M. (2016). Cross-linked superfine electrospun tragacanth-based biomaterial as scaffolds for tissue engineering. Paper presented at eCM Meeting Abstracts 2016, Collection 1, Towards Future Regenerative Therapies TERMIS-EU 2016 Conference, June 28 - July 1, Uppsala, Sweden. European Cells and Materials, 31(Suppl. 1), 204-204
Open this publication in new window or tab >>Cross-linked superfine electrospun tragacanth-based biomaterial as scaffolds for tissue engineering
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2016 (English)In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 31, no Suppl. 1, p. 204-204Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Natural polymer-based nanofibrous structures promote cell adhesion and proliferation due to their high surface area/volume ratio, high porosity, and similarity to native extracellular matrix in terms of both chemical composition and physical structure. Gum tragacanth (Tg) is a natural polysaccharides obtained from plants. It is a biocompatible, biodegradable and anionic polysaccharides that has been used extensively as an emulsifier in food and pharmaceutical industries. Despite, its good rheological properties and compatibility, the potential biomedical applications of Tg have not been fully investigated. The objective of the present study was to explore the feasibility of combining Tg with gelatin to fabricate a scaffold that serves as a simple collagen-glycosaminoglycans analog for tissue engineering applications, e.g. as a scaffold for human skin epithelial cells.

Place, publisher, year, edition, pages
Davos, Switzerland: AO Research Institute Davos, 2016
National Category
Nano Technology
Identifiers
urn:nbn:se:liu:diva-151904 (URN)
Conference
eCM Meeting Abstracts 2016, Collection 1, Towards Future Regenerative Therapies TERMIS-EU 2016 Conference, June 28 - July 1, Uppsala, Sweden
Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2018-10-19Bibliographically approved
Ravichandran, R., Islam, M. M., Alarcon, E. I., Samanta, A., Wang, S., Lundström, P., . . . Phopase, J. (2016). Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications. Journal of materials chemistry. B, 4(2), 318-326
Open this publication in new window or tab >>Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
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2016 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, no 2, p. 318-326Article in journal (Refereed) Published
Abstract [en]

In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2016
National Category
Physical Sciences Chemical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124491 (URN)10.1039/c5tb02035b (DOI)000367335200016 ()
Note

Funding Agencies|Swedish Research Council [621-2012-4286, 521-2012-5706]; NSERC; UOHI

Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30
Mondal, D., Griffith, M. & Venkatraman, S. S. (2016). Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges. International Journal of Polymeric Materials, 65(5), 255-265
Open this publication in new window or tab >>Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges
2016 (English)In: International Journal of Polymeric Materials, ISSN 0091-4037, E-ISSN 1563-535X, Vol. 65, no 5, p. 255-265Article in journal (Refereed) Published
Abstract [en]

Recently, poly (epsilon-caprolactone) (PCL) has gained a lot of attention, and shown great potential in biomedical applications. Among synthetic polymers, PCL is one of the easiest to process and manipulate into a large range of shapes and sizes due to its low melting temperature and its superior viscoelastic properties. In this review article the authors focus mainly on the properties of PCL-based biomaterials relevant to drug delivery and tissue engineering applications. The authors provide an insight into the recent developments and challenges of PCL-based biomaterials as a critical component of new therapeutic strategies for many diseases.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS AS, 2016
Keywords
Biomaterial; drug delivery; polycaprolactone; scaffold; tissue engineering
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124477 (URN)10.1080/00914037.2015.1103241 (DOI)000367841400003 ()
Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30
Ron-Doitch, S., Sawodny, B., Kuehbacher, A., Nordling David, M. M., Samanta, A., Phopase, J., . . . Rupp, S. (2016). Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV. Journal of Controlled Release, 229, 163-171
Open this publication in new window or tab >>Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV
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2016 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 229, p. 163-171Article in journal (Refereed) Published
Abstract [en]

Cationic antimicrobial peptides (AMPs) are part of the innate immunity, and act against a wide variety of pathogenic microorganisms by perturbation of the microorganisms plasma membrane. Although attractive for clinical applications, these agents suffer from limited stability and activity in vivo, as well as non-specific interaction with host biological membranes, leading to cytotoxic adverse effects. We hypothesized that encapsulation of AMPs within liposomes could result in reduced cytotoxicity, and with enhanced stability as well as bioactivity against herpes simplex virus 1 (HSV-1). We formulated nano-sized liposomal formulations of LL-37 and indolicidin, and their physicochemical properties, cellular uptake, in vitro cytotoxicity and antiviral efficacy have been determined. Lower cytotoxicity of LL-37 liposomes was found in comparison to indolicidin liposomes attributed to the superior physicochemical properties, and to the different degree of interaction with the liposomal membrane. The disc-like shaped LL-37 liposomes (106.8 +/- 10.1 nm, shelf-life stability of N1 year) were taken up more rapidly and to a significantly higher extent than the free peptide by human keratinocyte cell line (HaCaT), remained intact within the cells, followed by release of the active peptide within the cytoplasm and migration of the vesicles lipids to the plasma membrane. LL-37 liposomes were found significantly less toxic than both the free agent and liposomal indolicidin. In the new 3D epidermis model (immortalized primary keratinocytes) liposomal LL-37 treatment (N20 mu M), but not free LL-37, efficiently protected the epidermis, inhibiting HSV-1 infection. This positive antiviral effect was obtained with no cytotoxicity even at very high concentrations (400 mu M). Thus, the antiviral activity of encapsulated LL-37 was significantly improved, expanding its therapeutic window. Liposomal LL-37 appears to be a promising delivery system for HSV therapy. (C) 2016 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2016
Keywords
Drug delivery system; Liposomes; Antimicrobial peptides; LL-37; Indolicidin; Peptide delivery; Disc-like liposomes; HSV-1; 3D epidermis model
National Category
Physical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128724 (URN)10.1016/j.jconrel.2016.03.025 (DOI)000375218900015 ()27012977 (PubMedID)
Note

Funding Agencies|Fraunhofer Institute (Germany) - Hebrew University of Jerusalem (Israel); Sir Zelman Cowen Universities Fund

Available from: 2016-06-01 Created: 2016-05-30 Last updated: 2017-05-01
Islam, M. M., Ravichandran, R., Olsen, D., Kozak Ljunggren, M., Fagerholm, P., Lee, C.-J., . . . Phopase, J. (2016). Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation. RSC Advances, 6(61), 55745-55749
Open this publication in new window or tab >>Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation
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2016 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, no 61, p. 55745-55749Article in journal (Refereed) Published
Abstract [en]

Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potentially ideal substitutes. Self-assembling collagen-like-peptides conjugated with PEG-maleimide were assembled into hydrogels. When tested pre-clinically as corneal implants in mini-pigs, they promoted cell and nerve regeneration, forming neo-corneas structurally and functionally similar to natural corneas.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2016
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-130324 (URN)10.1039/c6ra08895c (DOI)000378275400008 ()
Note

Funding Agencies|Vinnova Indo-Sweden grant [2013-04645]; Integrative Regenerative Medicine Centre, Linkoping University (LiU); Region Ostergotland; Swedish Research Council grant [621-2012-4286]

Available from: 2016-07-29 Created: 2016-07-28 Last updated: 2017-11-28
Paaske Utheim, T., Islam, R., Fostad, I. G., Eidet, J. R., Sehic, A., Olstad, O. K., . . . Pasovic, L. (2016). Storage Temperature Alters the Expression of Differentiation-Related Genes in Cultured Oral Keratinocytes. PLoS ONE, 11(3), e0152526
Open this publication in new window or tab >>Storage Temperature Alters the Expression of Differentiation-Related Genes in Cultured Oral Keratinocytes
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, p. e0152526-Article in journal (Refereed) Published
Abstract [en]

Purpose Storage of cultured human oral keratinocytes (HOK) allows for transportation of cultured transplants to eye clinics worldwide. In a previous study, one-week storage of cultured HOK was found to be superior with regard to viability and morphology at 12 degrees C compared to 4 degrees C and 37 degrees C. To understand more of how storage temperature affects cell phenotype, gene expression of HOK before and after storage at 4 degrees C, 12 degrees C, and 37 degrees C was assessed. Materials and Methods Cultured HOK were stored in HEPES-and sodium bicarbonate-buffered Minimum Essential Medium at 4 degrees C, 12 degrees C, and 37 degrees C for one week. Total RNA was isolated and the gene expression profile was determined using DNA microarrays and analyzed with Partek Genomics Suite software and Ingenuity Pathway Analysis. Differentially expressed genes (fold change > 1.5 and P < 0.05) were identified by one-way ANOVA. Key genes were validated using qPCR. Results Gene expression of cultures stored at 4 degrees C and 12 degrees C clustered close to the unstored control cultures. Cultures stored at 37 degrees C displayed substantial change in gene expression compared to the other groups. In comparison with 12 degrees C, 2,981 genes were differentially expressed at 37 degrees C. In contrast, only 67 genes were differentially expressed between the unstored control and the cells stored at 12 degrees C. The 12 degrees C and 37 degrees C culture groups differed most significantly with regard to the expression of differentiation markers. The Hedgehog signaling pathway was significantly downregulated at 37 degrees C compared to 12 degrees C. Conclusion HOK cultures stored at 37 degrees C showed considerably larger changes in gene expression compared to unstored cells than cultured HOK stored at 4 degrees C and 12 degrees C. The changes observed at 37 degrees C consisted of differentiation of the cells towards a squamous epithelium-specific phenotype. Storing cultured ocular surface transplants at 37 degrees C is therefore not recommended. This is particularly interesting as 37 degrees C is the standard incubation temperature used for cell culture.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127566 (URN)10.1371/journal.pone.0152526 (DOI)000373113900072 ()27023475 (PubMedID)
Note

Funding Agencies|Department of Oral Biology, Faculty of Dentistry, University of Oslo; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

Available from: 2016-05-04 Created: 2016-05-03 Last updated: 2017-11-30
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1222-6720

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