Inducing Vascular Anastomosis for Vascular Tissue Transplantation and Vascular Regeneration: In Vitro Models and Factors

Document Type : Review


Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.


Anastomosis is a term which means a connection between two tubes or branched passages.Veins and arteries connect to transport blood in the body and this connection is natural anastomosis Whenever a blood vessel becomes blocked anastomosis is a backup pathway for blood flow. As the number of patients with chronic organ failure is increasing there is also a rapid increase in the demand for organ transplantation. As a result of a complicated mechanisms in different studies , activation of some factors including  FLT1 (Fms Related Receptor Tyrosine Kinase 1), macrophages, fibroblast, hypoxia, platelet drive growth factor, fibrin-based tissue ,mature vessel networks ,VEGF( Vascular endothelial growth factor) and mechanical processes are been inducing factors for vascular anastomosis. Certainly, vascular anastomosis models are necessary for in vitro vascular anastomosis formation to cover vessels with perivascular cells in a microfluidic device or discover new surgery techniques. In this study, an attempt was made to collect effective factors in inducing vascular anastomosis.


All vertebrates need blood vessels for tissue homeostasis. Neoangiogenesis which means new vessel growth is an essential process in wound repair to overcome tissue ischemia (1). Neo-angiogenesis also has some undesirable effects, such as tumor expansion. Also, whenever neo-angiogenesis becomes nonproductive and fails to oxygenate ischemic tissues, the underlying disease progresses, such as: diabetic retinopathy. Anastomosis is a term which means a connection between two tubes or branched passages (2).
Veins and arteries connect to transport blood in the body and this connection is natural anastomosis 

Whenever a blood vessel becomes blocked anastomosis is a backup pathway for blood flow (3). As the number of patients with chronic organ failure is increasing there is also a rapid increase in the demand for organ transplantation(4).A critical problem in transplantation, including liver and kidney, is organ shortage (5).Creating transplantable organ/tissue grafts in Vito is a solution for this organ shortage (6).
In recent years researchers have worked to make transplantable bioengineered tissue grafts in vitro (7). Rapid blood perfusion is necessary in maintenance of implanted tissue grafts after transplantation and this can be achieved by creating vascular anastomosis(8). In this study, an attempt was made to collect effective factors in inducing vascular anastomosis.

Literature review
Circulatory anastomoses
There are two approaches for creating vascular anastomosis. Circulatory anastomosis means natural anastomosis between many arteries; for example, the inferior epigastric artery and superior epigastric artery, or the anterior and / or posterior communicating arteries in the Circle of Willis (9).The circulatory anastomosis consisted of arterial and venous anastomosis. There are two types of arterial anastomosis: actual arterial anastomosis (e.g.  palmar arch, plantar arch) and potential arterial anastomosis (e.g. coronary arteries and cortical branch of cerebral arteries)(9). Whenever large blood supply is not needed anastomoses can help regulate systemic blood flow by forming alternative routes around capillary beds (10,11).

In deceased donor transplantation cold ischemia time (CIT) has been cited as an important and independent risk factor for delayed graft function (DGF)(12). Graft survival and function is also poor in DGF. DGF causes long hospital stay and more resource use (13).
WIT is an interesting research area and studies about warm ischemia time (WIT) effects on DGF are few. In live donor transplantation long WITs reduces graft survival. WITs are two types : organ procurement time and vascular anastomosis time (AT)(14).Vascular anastomosis should be secure without thrombosis. Uncertain sutures cause bleeding and pseudoaneurysm formation. Antithrombotic failure causes early anastomosis occlusion and intimal thickening and anastomosis stenosis (15). Anastomosis site and method and suturing procedure all are important in vascular anastomosis formation (16).

The difference between angiogenesis and anastomose
One of the fundamental processes in vertebrate developments is the formation of new blood vessels, which is of two types, vasculogenesis and angiogenesis(17). Angiogenesis is the main vessel forming process, and it typically involves new endothelial cells generating from earlier blood vessels (i.e., formed during vasculogenesis)(18).
 It is still uncertain how blood vessel networks spread out and are controlled afterwards. In angiogenesis, new vessel sprouts join together to reach perfusion. This process is referred to as angiogenesis(19). 
The matrix is where the vessels sprout into and generate perfused bridging connections. This device produces correct synopses of in vitro anastomosis to be utilized for studying angiogenesis and new drug screening approaches(20, 21)






































literature review 
 is a hospital based prospective study done in a tertiarycentre. Thirty patients with tibial plateau fractures who were operated with locking plates between 2015 and 2016 were followed for 18 months.Consent was taken from each patient before their participation in the study. 
After proper evaluation in the emergency department all patients underwent Xrays and CT scan for proper delineation of fracture site.Patients of either sex above 18 years with radiological evidence of tibial plateau fractures were considered for the study. Patients who had pre-existing arthritis of knee, congenital anomalies of knee, any previous surgery of the same knee, open trauma, those with compartment syndrome of the ipsilateral leg and polytrauma patients were not included in the study.
Patients who had pre-existing arthritis of knee, congenital anomalies of knee, any previous surgery of the same knee, open trauma, those with
compart ment syndrome of the ipsilateral leg and polytrauma patients were not included in the study.
Depending on the fracture type and site, two aplowing surgery, knee range of motions was started as soon as pain subsided usually after 2nd post op day.Postoperatively all patients were assessed after discharge at 2 weeks. Then four weekly till bony union occurred and after that three monthly till last follow up at 18 months.The functional outcome was evaluated using Rasmussen Functional Knee Score (Table 1) which was further graded according to score into Excellent, Good, Fair and Poor6.Post traumatic arthritic changes were graded according to Kellgren Lawrence grading. At 18 months all patients were checked clinically for limb malalignment.
Patients were also interviewed at 18 months regarding return to work. Sample size was 30. Chi square test and ANOVA test was used to calculate p-value depending on categorical and numerical data. Any p-value calculated < 0.05 was taken to be significant. Standard statistical analysis was done using SPSS version 18.

This prospective study was conducted at Central Institute of Orthopaedics, Safdarjung Hospital, New Delhi, India during the period of January 2015 to June 2017. Thirty patients withaverage age 42.4yearswith tibial plateau fractures were enrolled for the study which were fixed with open reduction and internal fixation with locking compression plates (Figure 1).



























The present study showed that the prevalence of febrile seizures was associated with gender, living place, temperature, family history of seizure, and the serum level of zinc. In this regard, the frequency of zinc deficiency was higher in patients with febrile seizures compared to febrile patients without seizure, before and after adjusting for gender. 
Zinc plays a vital role in the neuronal terminals of the hippocampus and amygdala by producing pyridoxal phosphate and affecting glutamatergic, gamma-aminobutyric acidergic (GABAergic), and glycinergic synapses (13).
Glutamic acid decarboxylase (GAD) acts as a major inhibitory neurotransmitter in the synthesis of gamma-aminobutyric acid (GABA) (14). A study by Ganesh R. and Janakiraman L. on 38 children with febrile convulsion and 38 children as a control group, aged between 3 months and 5 years, indicated that a serum zinc deficiency was significantly more prevalent in their case group than in the control group (15). Another study has reported that there is a correlation between disruption in Zn2+ homeostasis and fever seizure (16).
In studies by Papierkowski A., Mollah M.A., and Gündüz Z. et al., the mean serum zinc level in the febrile convulsion group was significantly lower than in the control group, which indicates the role of zinc in febrile seizure. Comparing the groups in terms of age and gender, no significant difference was found, similar to our study (17-19). Abdel Hameed Z.A. et al. (20), in a study on 100 infants in Egypt, observed that temperature had no significant difference between the case and control groups. But Berg A.T. (21), Ahmed B.W. (22), and our study showed the importance of temperature in febrile seizure. The geographic area can be the cause of this difference. Duangpetsang J. in a study from 2014 to 2017 reported that a high fever with electrolyte disturbance hyponatremia has an important role in FS (23). Sharifi R. et al., in a study in 2007-2014, showed the importance of family history in febrile seizure (24), which is similar to our results.

The findings of this study show that zinc deficiency is significantly associated with the occurrence of febrile seizures. Zinc supplementation in children can therefore be helpful for the prevention and treatment of FS.

Conflict of interest
The authors declare no conflicts of interest.


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