Calcification Causing Failure of Tissue Engineered Bovine Pericardium After Aortic Valve Repair

CardioCel® is bovine pericardium which is subjected to a novel tissue engineering process (ADAPT®) to reduce cytotoxicity and retard calcification while maintaining strength and elasticity. We present a case where CardioCel® showed rapid degeneration and calcification after repair of an aortic valve.

391 First CARMAT implantation in Italy: a nurse’s experience

Aims CARMAT is a new fully implantable device that simulates heart function. CARMAT has three characteristics that allow a physiological simulation that is at the top of biomedical engineering: it is blood-compatible for the use of bovine pericardium; it is pulsatile because it has hydraulic pumps that mimic systole and diastole; it is capable of self-regulating with the physiological needs of the patient. CARMAT has four biological valves that allow the intake of cardioaspirin avoiding the use of Coumadin and continuous blood draw. CARMAT also has two hybrid membranes with an internal part formed by bovine pericardium and an external polyurethane membrane; CARMAT has self-regulation sensors that adapt the system to the patient’s efforts. The operation is relatively simple because the rollers placed inside move the silicondressingstely and so it pushes the walls creating systole and diastole not synchronously as it normally happens but asynchronously, one ventricle at a time. Evaluation of the patient’s haemodynamics, monitoring of vital parameters, dressings of the drive-line, and psychological state. Methods and results Training in the field by the manufacturer due to the absence of material in literature. Since it was the first CARMAT implantation in Italy, we tried to combine experience with the clinical practice of other artificial hearts. The patient was weaned from anesthesia early and extubated; the patient did not show neurological damage. Psychologically, the artificial heart was accepted without any problems by the patient, the drive line had no infections, and the patient was discharged quickly. Conclusions The CARMAT system appears to be the one that best simulates the physiology of the heart because it involves fewer complications than other artificial hearts. This device is used as a bridge to transplant, but research and continuous studies tend to transform it as a therapy to end for patients who leave the transplant list and therefore the possibility of having a heart transplant.

Yak Pericardium as an Alternative Biomaterial for Transcatheter Heart Valves

Transcatheter aortic valve implantation (TAVI) has received much attention and development in the past decade due to its lower risk of complication and infections compared to a traditional open thoracotomy. However, the current commercial transcatheter heart valve does not fully meet clinical needs; therefore, new biological materials must be found in order to meet these requirements. We have discovered a new type of biological material, the yak pericardium. This current research studied its extracellular matrix structure, composition, mechanical properties, and amino acid content. Folding experiment was carried out to analyze the structure and mechanics after folding. We also conducted a subcutaneous embedding experiment to analyze the inflammatory response and calcification after implantation. Australian bovine pericardium, local bovine pericardium, and porcine pericardium were used as controls. The overall structure of the yak pericardium is flat, the collagen runs regularly, it has superior mechanical properties, and the average thickness is significantly lower than that of the Australian bovine and the local bovine pericardium control groups. The yak pericardium has a higher content of elastic fibers, showing that it has a better compression resistance effect during the folding experiment as well as having less expression of transplantation-related antigens. We conducted in vivo experiments and found that the yak pericardium has less inflammation and a lower degree of calcification. In summary, the yak pericardium, which is thin and strong, has lower immunogenicity and outstanding anti-calcification effects may be an excellent candidate valve leaflet material for TAVI.

Time scale of glycation in collagen of bovine pericardium-derived bio-tissues

Glycosylation is the process of combining one or more glucose molecules (or other monosaccharides) with molecules of a different nature (which are therefore glycosylated). In biochemistry, glycosylation is catalyzed by several specific enzymes, and assumes considerable importance since it occurs mainly at the expense of proteins and phospholipids which are thus transformed into glycoproteins and glycolipids. Conversely, in diabetes and aging, glycation of proteins is a phenomenon of non-enzymatic nature and thus not easily controlled. Glycation of collagen distorts its structure, renders the extracellular matrix stiff and brittle and at the same time lowers the degradation susceptibility thereby preventing renewal. Based on models detailed in this paper and with parameters determined from experimental data, we describe the glycation of type 1 collagen in bovine pericardium derived bio-tissues, upon incubation in glucose and ribose. With arginine and lysine/hydroxylysine amino acids as the primary sites of glycation and assuming that the topological polar surface area of the sugar molecules determines the glycation rates, we modelled the glycation as a function of time and determined the glycation rate and thus the progression of glycation as well as the resulting volume increase.

Dye-Mediated Photo-Oxidation Biomaterial Fixation: Analysis of Bioinductivity and Mechanical Properties of Bovine Pericardium for Use in Cardiac Surgery

Extracellular matrix bioscaffolds can influence the cardiac microenvironment and modulate endogenous cellular mechanisms. These materials can optimize cardiac surgery for repair and reconstruction. We investigated the biocompatibility and bioinductivity of bovine pericardium fixed via dye-mediated photo-oxidation on human cardiac fibroblast activity. We compared a dye-mediated photo-oxidation fixed bioscaffold to glutaraldehyde-fixed and non-fixed bioscaffolds reported in contemporary literature in cardiac surgery. Human cardiac fibroblasts from consenting patients were seeded on to bioscaffold materials to assess the biocompatibility and bioinductivity. Human cardiac fibroblast gene expression, secretome, morphology and viability were studied. Dye-mediated photo-oxidation fixed acellular bovine pericardium preserves human cardiac fibroblast phenotype and viability; and potentiates a pro-vasculogenic paracrine response. Material tensile properties were compared with biomechanical testing. Dye-mediated photo-oxidation fixed acellular bovine pericardium had higher compliance compared to glutaraldehyde-fixed bioscaffold in response to tensile force. The biocompatibility, bioinductivity, and biomechanical properties of dye-mediated photo-oxidation fixed bovine pericardium demonstrate its feasibility as a bioscaffold for use in cardiac surgery. As a fixed yet bioinductive solution, this bioscaffold demonstrates enhanced compliance and retains bioinductive properties that may leverage endogenous reparative pathways. Dye-mediated photo-oxidation fixed bioscaffold warrants further investigation as a viable tool for cardiac repair and reconstruction.

Haemocompatibility testing allows selective adaption of GA-free SULEEI-preparation strategy for bovine pericardium

Background/Introduction Bovine pericardium is the main natural source for patches or valve substitutes in cardiac surgery, but still, long-term durability is limited. An alternative, glutaraldehyde (GA)-free preparation combining decellularization, riboflavin/UVA crosslinking, and low-energy electron irradiation (SULEEI) procedure was established to avoid this. Protocol optimization is ongoing to further improve the final material. Haemocompatibility in vitro testing with fresh, human whole blood has advantages for material analysis, as it provides essential information on the activation of the complement system and immune cells therefore substantiating and possibly reducing the amount of animal testing. Purpose The haemocompatibility testing system was applied to reveal advantageous protocol adaptation of GA-free SULEEI preparation of pericardia. Methods Decellularized bovine pericardia were UVA-crosslinked in riboflavin/dextran solution. Protocol SULEEI B adaption includes the addition of trypsin in decellularization buffer and a 10x reduced riboflavin/dextran concentration during prolonged UVA irradiation with reduced intensity. Electron irradiation with 36 kGy was retained. Pericardia were incubated in blood chambers with heparinized human blood (2h, 37°C, GA-fixed/native controls). Inflammation (granulocyte loss and activation [CD11b]), complement activation (C5a) and haemostasis parameters (F1+2, PF4, granulocyte/platelet conjugates, platelet loss) were analyzed via flow cytometry or ELISA. Surface cell adhesion was investigated immunohistologically and via REM-analyses. Nuclear fragments were quantified in HE-stained sections. Results Haemostasis parameters F1+2 and PF4 were significantly higher in SULEEI A-pericardium (133±25 nmol/l and 1507±677 U/ml) vs. GA-fixation (2.9±2.9 nmol/l and 320±160 U/ml). Also, granulocyte/platelet conjugates (76.3±18.8%) and platelet loss (40.4±29.7%) were significantly higher after SULEEI A preparation in comparison to GA-fixation (39.3±9.9% and 20.5±6.4%). SULEEI B treated pericardia did not differ significantly. C5a complement activation was significantly lower in SULEEI A samples but comparable in SULEEI B to GA-fixed material. This is in contrast to a higher rate of nuclear fragments in SULEEI A tissue HE stained sections. Granulocyte activation of SULEEI pericardium (A: 89.8±29.7%; B: 106.2±18.8%) was significantly higher compared to native (46.1±22.6%) and for SULEEI B higher than in GA-fixed samples (67.2±9%). Granulocyte loss was comparable to GA-fixed pericardium after SULEEI B protocol. REM-analyses and histological evaluation visualized a dense blood cell and fibrin covering particular of SULEEI A-pericardium. Conclusions Haemocompatibility testing reveals advantageous properties of SULEEI B-pericardium. The impact of treatment substances such as dextran on high inflammatory response and dense surface covering in SULEEI A protocol is focus in ongoing experiments. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU/EFRE

Clinical Pilot Series of Non-Self-Contained Periodontal Infrabony Defects Treated with a Slowly Resorbable Bovine Pericardium Membrane in Combination with Low-Temperature-Treated Decellularized Bovine Bone Particles

The aim of this case series was to present the clinical outcomes of non-contained intrabony periodontal defects (IPDs) treated by means of papillary preservation flaps in association with a slowly resorbable bovine pericardium membrane (BPM) and a low-temperature-treated bovine bone graft (BBG). Eight healthy, non-smoking patients (two males and six females, mean age 48 ± 8 years) with stage 3 periodontitis and at least one site with residual probing depth (PD) ≥ 6 mm associated with a non-contained IPD ≥ 3 mm were treated. Two weeks after surgery, no adverse events were observed, and an early wound healing score (EHS) of 8.1 ± 1.0 was recorded. After 1 year, the mean probing depth (PD) reduction and mean clinical attachment level gain (CAL-gain) accounted for 4.8 ± 0.7 and 3.5 ± 0.7 mm, respectively, whereas the mean gingival recession (REC) was of 1.2 ± 0.3 mm. Radiographic bone fill was observed in all cases. In conclusion, the treatment of non-contained IPDs with a slowly resorbable BPM and a low-temperature-treated BBG could be considered safe and may result in significant clinical improvements 1 year after surgery.