Formation of eyeball orbital stump using titanium nickelide tissue-engineered construct and autologous blood mononuclear leukocytes

Objective: to study the morphological features of formation of the eyeball orbital stump using a titanium nickelide  tissue-engineered construct and a suspension of autologous blood mononuclear leukocytes in vivo. Materials  and methods. Experiments were performed on 54 sexually mature Wistar rats weighing 200–250 g. The animals   were divided into 3 groups, depending on type of surgical intervention: group 1 (n = 18) consisted of animals in  which eyeball orbital stump was formed after evisceroenucleation through implantation of a titanium nickelide  tissue-engineered construct and a suspension of autologous blood mononuclear leukocytes in the scleral sac; group  2 (n = 18) – the eyeball orbital stump was formed through implantation of titanium nickelide tissue-engineered  construct in the scleral sac; group 3 (n = 18) – orbital stump was formed using an Alloplant implant. Results.  It was established that in group 1 rats, on day 7 following surgery, the specific volume of connective tissue was  7.9 times (р_U = 0.048) higher than in group 2 rats and 15.8 times (р_U = 0.039) higher than in group 3 rats. On  day 14 after surgery, the volume of connective tissue in the eyeball orbital stump of group 1 rats reached the highest  value compared to that in the other groups. The numerical density of newly formed vessels in the eyeball orbital  stump of group 1 rats, starting from day 14 after surgery up to the end of experiment (day 21), was statistically  significantly higher than that in the other groups. Moreover, on day 21, this indicator was 4.0 times (р_U = 0.001)  higher in group 1 rats than in group 2 rats and 9.8 times (р_U = 0,0003) higher than in group 3 rats. Conclusion.  Implantation of titanium nickelide tissue-engineered construct and a suspension of autologous blood mononuclear  leukocytes into the scleral sac after evisceroenucleation in an in vivo experiment leads to accelerated maturation  of the connective tissue and intensive vascularization in the eyeball orbital stump. This ensures strong fixation of  the implant and reduces risk of rejection.

1. Schmitzer S, Simionescu C, Alexandrescu C, Burcea M. The Anophthalmic Socket – Reconstruction Options. Journal of Medicine and Life. 2014; 7 (Spec Iss 4): 23–29.

2. Barash AN, Sharshakova TM, Malinovskij GF. Mediko-social’nye problemy pri anoftal’micheskom sindrome. Problemy zdorov’ja i jekologii. 2015; 44 (2): 4–7.

3. Tihookeanskij medicinskij zhurnal. 2016; 3 (65): 32–36. doi: 10.17238/PmJ1609-1175.2016.3.32–36.

4. Bohman E, Roed Rassmusen ML, Kopp ED. Pain and discomfort in the anophthalmic socket. Curr Opin Ophthalmol. 2014; 25 (5): 455–460. doi: 10.1097/ICU.0000000000000069.

5. Ivolgina IV. Osobennosti primenenija razlichnyh implantatov pri formirovanii opornodvigatel’noj kul’ti posle jenukleacii. Vestnik TGU. 2015; 20 (3): 577–579.

6. Mezen NI. Stvolovye kletki: ucheb.-metod. posobie. Minsk: BGMU, 2014: 62.

7. Gilevich IV, Polyakov IS, Porkhanov VA, Chekhonin VP. Morphological Analysis of Biocompatibility of Autologous Bone Marrow Mononuclear Cells with Synthetic Polyethylene Terephthalate Scaffold. Bulletin of Experimental Biology and Medicine. 2017; 163 (3): 400–404. [In Russ, English abstract]. doi: 10.1007/s10517-017-3813-z.

8. Lyzikov AN, Osipov BB, Skuratov AG, Prizencov AA. Stvolovye kletki v regenerativnoj medicine: dostizhenija i perspektivy. Problemy zdorov’ja i jekologii. 2015; 45 (3): 4–9.

9. Rjabov SI, Zvjaginceva MA, Osidak EO, Smirnov VA. Kollagenovyj implantat i mononuklearnye kletki pupovinnoj krovi pozvoljajut vosstanovit’ dvizhenie zadnih konechnostej posle udalenija uchastka spinnogo mozga. Bjulleten’ jeksperimental’noj biologii i mediciny. 2017; 164 (9): 377–380.

10. Subbot AM, Kasparova EA. Obzor podhodov k kletochnoj terapii v oftal’mologii. Vestnik oftal’mologii. 2015; 5: 74–81.

11. Bedian L, Rodriguez AMV, Vargas GH, Parra-Saldivar R, Iqbal HM. Bio-based materials with novel characteristics for tissue engineering applications – a review. Int J Biol Macromol. 2017; 98: 837– 846. doi: 10.1016/j.ijbiomac.2017.02.048.

12. Li MD, Atkins H, Bubela T. The global landscape of stem cell clinical trials. Regen Med. 2014 Jan; 9 (1): 27–39. doi: 10.2217/rme.13.80.

13. Gjunter VJe, Hodorenko VN, Chekalkin TL, Olesova GC, Dambaev PG, Sysoljatin NG i dr. Medicinskie materialy s pamjat’ju formy. Tomsk: MIC, 2011: 534.

14. Erichev VP, Petrov SY, Subbot АМ, Volzhanin AV, Germanova VN, Karlova ЕV. Role of cytokines in the pathogenesis of eye diseases. National Journal «Glaucoma». 2017;16 (1): 87–101. [In Russ, English abstract].

15. Hlusov IA, Nechaev KA, Dvornichenko MV, Hlusova MJu, Rjazanceva NV, Savel’eva OV i dr. Molekuljarnye mehanizmy reakcii stromal’nyh stvolovyh kletok i mononuklearnyh lejkocitov krovi na kratkovremennyj kontakt s iskusstvennymi materialami. Vestnik nauki Sibiri. 2012; 1: 321–327.

16. At’kova EL, Rejn DA, Jarcev VD, Subbot AM. Vlijanie citokina TGF-beta i drugih faktorov na process regeneracii. Vestnik oftal’mologii. 2017; 4: 89–96.