Fibrin plays an important role in wound healing and regeneration, and enjoys widespread use in surgery and tissue engineering. The enzymatic activity of Factor XIIIa was employed to covalently incorporate exogenous bioactive peptides within fibrin during coagulation. Fibrin gels were formed with incorporated peptides from laminin and N-cadherin alone and in combination at concentrations up to 8.2 mol peptide per mole of fibrinogen. Neurite extension in vitro was enhanced when gels were augmented with exogenous peptide, with the maximal improvement reaching 75%. When this particular fibrin derivative was evaluated in rats in the repair of the severed dorsal root within polymeric tubes, the number of regenerated axons was enhanced by 85% relative to animals treated with tubes filled with unmodified fibrin. These results demonstrate that it is possible to enhance the biological activity of fibrin by enzymatically incorporating exogenous oligopeptide domains of morphoregulatory proteins.

Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension.

https://tissueeng.net/lab/papers/2007%20JCR%20HH.pdf

Bone regeneration through controlled release of bone morphogenetic protein-2 from 3-D tissue engineered nano-scaffold.

Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis.

Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters.

Aims/hypothesis. This study examined the biological effects of the GIP receptor antagonist, (Pro(3))GIP and the GLP-1 receptor antagonist, exendin(9-39)amide. Methods Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic (ob/ob) mice. Results. In GIP receptor-transfected fibroblasts, (Pro(3))-GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin-(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) Mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%;p<0.001) from clonal BRIN-BD11 cells, but had no effect on GLP-1-stimulated insulin release. In contrast, exendin(9-39)amide inhibited both GIP and GLP-1-stimulated insulin release (57% and 44%, respectively; p<0.001). Administration of (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides (25 nmol/kg body weight, i.p.) to fasted (ob/ob) mice decreased the plasma insulin responses by 42%, 54% and 49%, respectively (p<;0.01 to p<0.001). The hyperinsulinaemia of non-fasted (ob/ob) mice was decreased by 19%, 27% and 18% (p<0.05 to p<0.01) by injection of (Pro(3))GIP, exendin(9-39)amide or combined peptides but accompanying changes of plasma glucose were small. Conclusions/interpretation. These data show that (Pro(3))GIP is a specific GIP receptor antagonist. Furthermore, feeding studies in one commonly used animal model of obesity and diabetes, (ob/ob) mice, suggest that GIP is the major physiological component of the enteroinsular axis, contributing approximately 80% to incretin-induced insulin release.

/pdf/effects-of-the-novel-pro-3-gip-antagonist-and-exendin-9-39-3izbw0s16d.pdf

Effects of the novel (Pro 3 )GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob /ob) mice: evidence that GIP is the major physiological incretin

R. L. Noble

Papers

Solid Phase Peptide Synthesis Utilizing 9-Fluorenylmethoxycarbonylamino Acids