ABSTRACT
Cryogels made of components of natural extracellular matrix components are potent biomaterials for bioengineering and regenerative medicine. Human dermal fibroblasts are key cells for tissue replacement during wound healing. Thus, any biomaterial for wound healing applications should enable growth, differentiation and matrix synthesis by these cells. Cryogels are highly porous scaffolds consisting of a network of interconnected pores. Here, we used a novel group of cryogels generated from acrylated hyaluronan where the polymerization was initiated by accelerated electrons (E-beam). This novel procedure omits any toxic polymerization initiators and results in sterile, highly elastic scaffolds with adjustable pore size, excellent swelling and low flow resistance properties. We show that these cryogels are effective 3D-substrates for long-term cultures of human dermal fibroblasts in vitro. The cells proliferate for at least 28days throughout the cryogels and deposit their own matrix in the pores. Moreover, key modulators of dermal fibroblasts during wound healing like TGFß and PDGF efficiently stimulated the expression of wound healing-relevant genes. In conclusion, electron beam initiated cryogels of acrylated hyaluronan represent a functional and cell compatible biomaterial that could be adapted for special wound healing applications by further functionalization.
Subject(s)
Acrylates/pharmacology , Cryogels/pharmacology , Electrons , Extracellular Matrix/metabolism , Fibroblasts/drug effects , Hyaluronic Acid/pharmacology , Acrylates/chemistry , Biocompatible Materials , Cell Proliferation/drug effects , Cryogels/chemical synthesis , Dermis/cytology , Dermis/metabolism , Elasticity , Extracellular Matrix/chemistry , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Hyaluronic Acid/chemistry , Male , Platelet-Derived Growth Factor/pharmacology , Polymerization , Porosity , Primary Cell Culture , Tissue Engineering , Tissue Scaffolds , Transforming Growth Factor beta/pharmacologyABSTRACT
Fat emulsions can cause changes in blood-clotting and fibrinolysis. The aim of this study was to examine the relation between the use of the short-acting hypnotic propofol and alteration of the blood clotting system. In a double-blind randomized study, 36 patients with an aortocoronary bypass operation were given either midazolam/fentanyl or propofol/alfentanil. Eleven blood samples were taken at fixed times pre-, intra- and postoperatively to determine changes caused by the anesthetic agents on the hemostaseologic parameters during the whole operation. Perioperative blood pressures of both groups were measured at seven fixed points. From the beginning of the extracorporeal circulation (ECC) to the end of the operation, the measured values of the factor XIIa- and kallikrein-like activity in the propofol group were significantly higher than those of the midazolam group. Also the values of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) suggest a stronger activation of the contact phase at the start of the recirculation and as a result of it a stronger fibrinolysis within the propofol group. Besides, the hypotensive side-effect in the propofol group was evident in contrast to the midazolam group. With this investigation, a correlation between the application of propofol/alfentanil, contact phase activation with activation of the kallikrein-kinin-bradykinin system and the observed hypotension can be set up.
Subject(s)
Anesthetics/pharmacology , Blood Coagulation/drug effects , Propofol/pharmacology , Adult , Aged , Alfentanil/administration & dosage , Alfentanil/pharmacology , Anesthetics/administration & dosage , Blood Pressure/drug effects , Double-Blind Method , Female , Fentanyl/administration & dosage , Fentanyl/pharmacology , Humans , Kallikrein-Kinin System/drug effects , Male , Midazolam/administration & dosage , Midazolam/pharmacology , Middle Aged , Propofol/administration & dosageABSTRACT
Perioperative haemodynamic changes leading to severe circulatory problems during open-heart surgery still represent dreaded complications. The aim of this study was to examine the relationship between the use of applied anaesthetic agents and alterations of the contact phase of the intrinsic blood-clotting system, as changes within the kallikrein-kinin system can lead to a fall in blood pressure. In a randomized study, parameters of the kallikrein-kinin system, coagulation and fibrinolysis were determined for 36 patients with aortocoronary bypass operations. The patients had been given either midazolam/fentanyl or propofol/alfentanil to maintain anaesthesia. Perioperative blood pressure values were registered at seven fixed points. The measured values of the factor XIIa-like activity and the kallikrein-like activity suggested a higher activation of the contact phase, when propofol/alfentanil was given. From the start of the extracorporeal circulation (ECC) to the end of the operation, the kallikrein-like activities in the propofol/alfentanil group were significantly higher than those of the midazolam/fentanyl group. Also, the results of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) indicate a stronger activation of the contact phase--at least at the beginning of recirculation--and as a result of it, a stronger fibrinolysis within the propofol/alfentanil group. In addition, the hypotensive side-effects differed significantly between the two groups. Patients receiving propofol/alfentanil needed the triple amount of antihypotonicum to maintain the mean arterial blood pressure above 75 mmHg. With the results of this study, a correlation between the application of propofol/alfentanil, contact phase activation, with activation of the kallikrein-kinin-bradykinin system and the observed hypotension, can be presumed.
