FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Head Face Med / Release kinetics of VEGF165 from a collagen matrix and struc...
Head & face medicine2010; 6; 17; doi: 10.1186/1746-160X-6-17

Release kinetics of VEGF165 from a collagen matrix and structural matrix changes in a circulation model.

Abstract: Current approaches in bone regeneration combine osteoconductive scaffolds with bioactive cytokines like BMP or VEGF. The idea of our in-vitro trial was to apply VEGF165 in gradient concentrations to an equine collagen carrier and to study pharmacological and morphological characteristics of the complex in a circulation model. Methods: Release kinetics of VEGF165 complexed in different quantities in a collagen matrix were determined in a circulation model by quantifying protein concentration with ELISA over a period of 5 days. The structural changes of the collagen matrix were assessed with light microscopy, native scanning electron microscopy (SEM) as well as with immuno-gold-labelling technique in scanning and transmission electron microscopy (TEM). Results: We established a biological half-life for VEGF165 of 90 minutes. In a half-logarithmic presentation the VEGF165 release showed a linear declining gradient; the release kinetics were not depending on VEGF165 concentrations. After 12 hours VEGF release reached a plateau, after 48 hours VEGF165 was no longer detectable in the complexes charged with lower doses, but still measurable in the 80 microg sample. At the beginning of the study a smear layer was visible on the surface of the complex. After the wash out of the protein in the first days the natural structure of the collagen appeared and did not change over the test period. Conclusions: By defining the pharmacological and morphological profile of a cytokine collagen complex in a circulation model our data paves the way for further in-vivo studies where additional biological side effects will have to be considered. VEGF165 linked to collagen fibrils shows its improved stability in direct electron microscopic imaging as well as in prolonged release from the matrix. Our in-vitro trial substantiates the position of cytokine collagen complexes as innovative and effective treatment tools in regenerative medicine and and may initiate further clinical research.
Get Full Text
Publication Date: 2010-07-19 PubMed ID: 20642842PubMed Central: PMC2913915DOI: 10.1186/1746-160X-6-17Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigated the release rate and structural changes of a Vascular Endothelial Growth Factor (VEGF165) complexed with a collagen matrix under circulation conditions as a potential treatment tool in regenerative medicine.

Study Purpose and Design

  • The goal of this in-vitro study was to examine the pharmacological and morphological characteristics of a complex composed of gradient concentrations of VEGF165, a bioactive cytokine, and an equine collagen carrier. This type of complex is being explored for its potential use in bone regeneration treatments.
  • To accomplish this, the researchers determined the release kinetics of VEGF165 from the collagen matrix in a circulation model over a period of 5 days. They measured the protein concentration using a technique called ELISA.
  • The researchers also assessed any structural changes in the collagen matrix using light microscopy, native scanning electron microscopy (SEM), and immuno-gold-labelling technique in scanning and transmission electron microscopy (TEM).

Key Findings

  • The researchers established a biological half-life for VEGF165 of 90 minutes. The term “biological half-life” refers to the time it takes for a substance to lose half of its pharmacologic or physiologic activity.
  • In a half-logarithmic presentation, the VEGF165 release followed a linear declining gradient. This means the rate of release decreased evenly over time, regardless of the initial VEGF165 concentration.
  • VEGF165 release reached a plateau after 12 hours and was undetectable in low-dose complexes after 48 hours. However, it was still measurable in an 80 microg sample.
  • The study found a smear layer on the surface of the complex at the start of the study. After the protein was washed out during the initial days, the natural structure of the collagen appeared and remained stable over the test period.

Conclusions and Significance

  • This study offers valuable data on the pharmacological and morphological characteristics of a cytokine-collagen complex in a circulation model. This supports further in-vivo studies to evaluate potential biological side effects.
  • The findings show that VEGF165 linked to collagen fibrils exhibited improved stability in direct electron microscopic imaging and had a prolonged release from the matrix.
  • The results affirm the role of cytokine collagen complexes as innovative and effective treatment tools in regenerative medicine, potentially sparking further clinical research in this area.

Cite This Article

APA
Kleinheinz J, Jung S, Wermker K, Fischer C, Joos U. (2010). Release kinetics of VEGF165 from a collagen matrix and structural matrix changes in a circulation model. Head Face Med, 6, 17. https://doi.org/10.1186/1746-160X-6-17

Publication

Head & face medicine
ISSN: 1746-160X
NlmUniqueID: 101245792
Country: England
Language: English
Volume: 6
Pages: 17

Researcher Affiliations

Kleinheinz, Johannes
  • Department of Cranio-Maxillofacial Surgery, Research Unit Vascular Biology of Oral, Structures, University Hospital Muenster, Waldeyerstrasse 30, D-48149 Muenster, Germany. Johannes.Kleinheinz@ukmuenster.de
Jung, Susanne
    Wermker, Kai
      Fischer, Carsten
        Joos, Ulrich

          MeSH Terms

          • Animals
          • Bone Regeneration / physiology
          • Collagen / metabolism
          • Cytokines / metabolism
          • Horses
          • Humans
          • In Vitro Techniques
          • Models, Animal
          • Vascular Endothelial Growth Factor A / metabolism

          References

          This article includes 27 references
          1. Reddi AH. Bone and cartilage differentiation.. Curr Opin Genet Dev 1994 Oct;4(5):737-44.
            doi: 10.1016/0959-437X(94)90141-Opubmed: 7849513google scholar: lookup
          2. Caplan AI. Cartilage begets bone versus endochondral myelopoiesis.. Clin Orthop Relat Res 1990 Dec;(261):257-67.
            pubmed: 2245556
          3. Kübler NR. [Osteoinduction and -reparation].. Mund Kiefer Gesichtschir 1997 Feb;1(1):2-25.
            doi: 10.1007/BF03043502pubmed: 9483923google scholar: lookup
          4. Schmidt K, Swoboda H. Die Bedeutung matrixgebundener Zytokine für die Osteoinduktion und Osteogenese. Implantologie 1995;2:127–148.
          5. Sauter ER, Nesbit M, Watson JC, Klein-Szanto A, Litwin S, Herlyn M. Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck.. Clin Cancer Res 1999 Apr;5(4):775-82.
            pubmed: 10213212
          6. Schliephake H, Jamil MU, Knebel JW. Experimental reconstruction of the mandible using polylactic acid tubes and basic fibroblast growth factor in alloplastic scaffolds.. J Oral Maxillofac Surg 1998 May;56(5):616-26; discussion 626-7.
            doi: 10.1016/S0278-2391(98)90463-3pubmed: 9590344google scholar: lookup
          7. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell-Braxton L, Hillan KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.. Nature 1996 Apr 4;380(6573):439-42.
            doi: 10.1038/380439a0pubmed: 8602242google scholar: lookup
          8. Kleinheinz J, Joos U. Serum concentration of VEGF and bFGF in patients with sagittal split ramus osteotomy. Int J Oral Maxillofac Surg 1999;28:539.
            doi: 10.1016/S0901-5027(99)80812-1google scholar: lookup
          9. Hollinger J, Wong ME. The integrated processes of hard tissue regeneration with special emphasis on fracture healing.. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996 Dec;82(6):594-606.
            doi: 10.1016/S1079-2104(96)80431-8pubmed: 8974129google scholar: lookup
          10. Mattei MG, Borg JP, Rosnet O, Marmé D, Birnbaum D. Assignment of vascular endothelial growth factor (VEGF) and placenta growth factor (PLGF) genes to human chromosome 6p12-p21 and 14q24-q31 regions, respectively.. Genomics 1996 Feb 15;32(1):168-9.
            doi: 10.1006/geno.1996.0098pubmed: 8786112google scholar: lookup
          11. Drake CJ, Little CD. Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization.. Proc Natl Acad Sci U S A 1995 Aug 15;92(17):7657-61.
            doi: 10.1073/pnas.92.17.7657pmc: PMC41204pubmed: 7543999google scholar: lookup
          12. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT. Vascular permeability factor, an endothelial cell mitogen related to PDGF.. Science 1989 Dec 8;246(4935):1309-12.
            doi: 10.1126/science.2479987pubmed: 2479987google scholar: lookup
          13. Plate KH, Breier G, Risau W. Molecular mechanisms of developmental and tumor angiogenesis.. Brain Pathol 1994 Jul;4(3):207-18.
            doi: 10.1111/j.1750-3639.1994.tb00835.xpubmed: 7524960google scholar: lookup
          14. Senger DR, Van de Water L, Brown LF, Nagy JA, Yeo KT, Yeo TK, Berse B, Jackman RW, Dvorak AM, Dvorak HF. Vascular permeability factor (VPF, VEGF) in tumor biology.. Cancer Metastasis Rev 1993 Sep;12(3-4):303-24.
            doi: 10.1007/BF00665960pubmed: 8281615google scholar: lookup
          15. Hutmacher D, Kirsch A, Ackermann K, Hürzeler M. Matrix and carrier for bone growth factors: state of the art and future perspectives. Berlin Heidelberg, Springer; 1998.
          16. Wang DS, Yamazaki K, Nohtomi K, Shizume K, Ohsumi K, Shibuya M, Demura H, Sato K. Increase of vascular endothelial growth factor mRNA expression by 1,25-dihydroxyvitamin D3 in human osteoblast-like cells.. J Bone Miner Res 1996 Apr;11(4):472-9.
            doi: 10.1002/jbmr.5650110408pubmed: 8992878google scholar: lookup
          17. Ramselaar M, Driessens F, Kalk W, De Wijn J, Van Mullem P. Biodegradation of four calcium phosphate ceramics; in vivo rates and tissue interactions. J Mat Sci 1991;2:63–70.
          18. Hemprich A, Lehmann R, Khoury F, Schulte A, Hidding J. [Filling cysts with type 1 bone collagen].. Dtsch Zahnarztl Z 1989 Aug;44(8):590-2.
            pubmed: 2639062
          19. Baslé MF, Lesourd M, Grizon F, Pascaretti C, Chappard D. [Type I collagen in xenogenic bone material regulates attachment and spreading of osteoblasts over the beta1 integrin subunit].. Orthopade 1998 Feb;27(2):136-42.
            pubmed: 9530670doi: 10.1007/s001320050211google scholar: lookup
          20. Burchardt H. Biology of bone transplantation.. Orthop Clin North Am 1987 Apr;18(2):187-96.
            pubmed: 3550571
          21. Crotts G, Park TG. Protein delivery from poly(lactic-co-glycolic acid) biodegradable microspheres: release kinetics and stability issues.. J Microencapsul 1998 Nov-Dec;15(6):699-713.
            doi: 10.3109/02652049809008253pubmed: 9818948google scholar: lookup
          22. Arnold F, West DC. Angiogenesis in wound healing.. Pharmacol Ther 1991 Dec;52(3):407-22.
            doi: 10.1016/0163-7258(91)90034-Jpubmed: 1726477google scholar: lookup
          23. Iruela-Arispe ML, Dvorak HF. Angiogenesis: a dynamic balance of stimulators and inhibitors.. Thromb Haemost 1997 Jul;78(1):672-7.
            pubmed: 9198237
          24. Kremer C, Breier G, Risau W, Plate KH. Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system.. Cancer Res 1997 Sep 1;57(17):3852-9.
            pubmed: 9288799
          25. Safi J Jr, DiPaula AF Jr, Riccioni T, Kajstura J, Ambrosio G, Becker LC, Anversa P, Capogrossi MC. Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart.. Microvasc Res 1999 Nov;58(3):238-49.
            doi: 10.1006/mvre.1999.2165pubmed: 10527767google scholar: lookup
          26. Franceschi RT. Biological approaches to bone regeneration by gene therapy.. J Dent Res 2005 Dec;84(12):1093-103.
            doi: 10.1177/154405910508401204pubmed: 16304438google scholar: lookup
          27. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb.. Lancet 1996 Aug 10;348(9024):370-4.
            doi: 10.1016/S0140-6736(96)03361-2pubmed: 8709735google scholar: lookup

          Citations

          This article has been cited 21 times.
          1. Berg M, Eleftheriadou D, Phillips JB, Shipley RJ. Mathematical modelling with Bayesian inference to quantitatively characterize therapeutic cell behaviour in nerve tissue engineering.. J R Soc Interface 2023 Sep;20(206):20230258.
            doi: 10.1098/rsif.2023.0258pubmed: 37669694google scholar: lookup
          2. Pasquiers B, Benamara S, Felices M, Ternant D, Declèves X, Puszkiel A. Translation of Monoclonal Antibodies Pharmacokinetics from Animal to Human Using Physiologically Based Modeling in Open Systems Pharmacology (OSP) Suite: A Retrospective Analysis of Bevacizumab.. Pharmaceutics 2023 Aug 14;15(8).
            doi: 10.3390/pharmaceutics15082129pubmed: 37631343google scholar: lookup
          3. Gallo N, Natali ML, Sannino A, Salvatore L. An Overview of the Use of Equine Collagen as Emerging Material for Biomedical Applications.. J Funct Biomater 2020 Nov 1;11(4).
            doi: 10.3390/jfb11040079pubmed: 33139660google scholar: lookup
          4. Coy R, Al-Badri G, Kayal C, O'Rourke C, Kingham PJ, Phillips JB, Shipley RJ. Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering.. J R Soc Interface 2020 Mar;17(164):20190801.
            doi: 10.1098/rsif.2019.0801pubmed: 32208821google scholar: lookup
          5. O'Dwyer J, Murphy R, Dolan EB, Kovarova L, Pravda M, Velebny V, Heise A, Duffy GP, Cryan SA. Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium.. Drug Deliv Transl Res 2020 Apr;10(2):440-454.
            doi: 10.1007/s13346-019-00684-5pubmed: 31691161google scholar: lookup
          6. Dao DT, Anez-Bustillos L, Pan A, O'Loughlin AA, Mitchell PD, Fell GL, Baker MA, Cho BS, Nandivada P, Nedder AP, Smithers CJ, Chen N, Comeau R, Holmes K, Kalled S, Norton A, Zhang B, Puder M. Vascular Endothelial Growth Factor Enhances Compensatory Lung Growth in Piglets.. Surgery 2018 Dec;164(6):1279-1286.
            doi: 10.1016/j.surg.2018.07.003pubmed: 30193736google scholar: lookup
          7. Vilanova G, Burés M, Colominas I, Gomez H. Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis.. J R Soc Interface 2018 Sep;15(146).
            doi: 10.1098/rsif.2018.0415pubmed: 30185542google scholar: lookup
          8. Lynn SA, Ward G, Keeling E, Scott JA, Cree AJ, Johnston DA, Page A, Cuan-Urquizo E, Bhaskar A, Grossel MC, Tumbarello DA, Newman TA, Lotery AJ, Ratnayaka JA. Ex-vivo models of the Retinal Pigment Epithelium (RPE) in long-term culture faithfully recapitulate key structural and physiological features of native RPE.. Tissue Cell 2017 Aug;49(4):447-460.
            doi: 10.1016/j.tice.2017.06.003pubmed: 28669519google scholar: lookup
          9. Vilanova G, Colominas I, Gomez H. A mathematical model of tumour angiogenesis: growth, regression and regrowth.. J R Soc Interface 2017 Jan;14(126).
            doi: 10.1098/rsif.2016.0918pubmed: 28100829google scholar: lookup
          10. Hauschild G, Geburek F, Gosheger G, Eveslage M, Serrano D, Streitbürger A, Johannlükens S, Menzel D, Mischke R. Short term storage stability at room temperature of two different platelet-rich plasma preparations from equine donors and potential impact on growth factor concentrations.. BMC Vet Res 2017 Jan 5;13(1):7.
            doi: 10.1186/s12917-016-0920-4pubmed: 28056978google scholar: lookup
          11. Bodnar M, Guerrero P, Perez-Carrasco R, Piotrowska MJ. Deterministic and Stochastic Study for a Microscopic Angiogenesis Model: Applications to the Lewis Lung Carcinoma.. PLoS One 2016;11(5):e0155553.
            doi: 10.1371/journal.pone.0155553pubmed: 27182891google scholar: lookup
          12. Barati D, Shariati SRP, Moeinzadeh S, Melero-Martin JM, Khademhosseini A, Jabbari E. Spatiotemporal release of BMP-2 and VEGF enhances osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells co-encapsulated in a patterned hydrogel.. J Control Release 2016 Feb 10;223:126-136.
            doi: 10.1016/j.jconrel.2015.12.031pubmed: 26721447google scholar: lookup
          13. Nyberg E, Holmes C, Witham T, Grayson WL. Growth factor-eluting technologies for bone tissue engineering.. Drug Deliv Transl Res 2016 Apr;6(2):184-94.
            doi: 10.1007/s13346-015-0233-3pubmed: 25967594google scholar: lookup
          14. Al-Habdan I, Sadat-Ali M, Safar Alghamdy M, Randhawa A, Chathoth S. Assessment of Pharmacokinetics and Toxicology of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) in Rats and Goats.. Int J Biomed Sci 2014 Sep;10(3):167-71.
            pubmed: 25324697
          15. Kwon H, Rainbow RS, Sun L, Hui CK, Cairns DM, Preda RC, Kaplan DL, Zeng L. Scaffold structure and fabrication method affect proinflammatory milieu in three-dimensional-cultured chondrocytes.. J Biomed Mater Res A 2015 Feb;103(2):534-44.
            doi: 10.1002/jbm.a.35203pubmed: 24753349google scholar: lookup
          16. Vempati P, Popel AS, Mac Gabhann F. Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning.. Cytokine Growth Factor Rev 2014 Feb;25(1):1-19.
            doi: 10.1016/j.cytogfr.2013.11.002pubmed: 24332926google scholar: lookup
          17. Kwon H, Sun L, Cairns DM, Rainbow RS, Preda RC, Kaplan DL, Zeng L. The influence of scaffold material on chondrocytes under inflammatory conditions.. Acta Biomater 2013 May;9(5):6563-75.
            doi: 10.1016/j.actbio.2013.01.004pubmed: 23333441google scholar: lookup
          18. Frey SP, Jansen H, Raschke MJ, Meffert RH, Ochman S. VEGF improves skeletal muscle regeneration after acute trauma and reconstruction of the limb in a rabbit model.. Clin Orthop Relat Res 2012 Dec;470(12):3607-14.
            doi: 10.1007/s11999-012-2456-7pubmed: 22806260google scholar: lookup
          19. Finley SD, Engel-Stefanini MO, Imoukhuede PI, Popel AS. Pharmacokinetics and pharmacodynamics of VEGF-neutralizing antibodies.. BMC Syst Biol 2011 Nov 21;5:193.
            doi: 10.1186/1752-0509-5-193pubmed: 22104283google scholar: lookup
          20. Yen P, Finley SD, Engel-Stefanini MO, Popel AS. A two-compartment model of VEGF distribution in the mouse.. PLoS One 2011;6(11):e27514.
            doi: 10.1371/journal.pone.0027514pubmed: 22087332google scholar: lookup
          21. Gomes S, Leonor IB, Mano JF, Reis RL, Kaplan DL. Natural and Genetically Engineered Proteins for Tissue Engineering.. Prog Polym Sci 2012 Jan 1;37(1):1-17.
            doi: 10.1016/j.progpolymsci.2011.07.003pubmed: 22058578google scholar: lookup
          Subscribe to our newsletter
          Join 99,383 horse owners like you who receive our email updates on horse health and nutrition.