HISTOLOGICAL STRUCTURE OF THE RAT FEMURS AFTER FILLING OF DEFECTS IN THE DISTAL METAPHYSIS WITH 3D-PRINTED IMPLANTS BASED ON POLYLACTIDE AND TRICALCIUM PHOSPHATE IN COMBINATION WITH MESENCHYMAL STROMAL CELLS
DOI:
https://doi.org/10.15674/0030-59872023343-50Keywords:
Rat model, bone defect, bone regeneration, additive technologies, polylactid, tricalcium phosphate, mesenchymal stromal cellAbstract
Polylactide (PLA) frameworks printed on a 3D printer are used for filling the bone defects. The osteotropic properties of 3D-PLA can be improved by combining with tricalcium phosphate (TCP) and mesenchymal stromal cells (MSCs). Objective. Study the reconstruction in the rat femurs after implanting 3D-printed implants based on PLA and TCP (3D-I) in combination with cultured allogeneic MSCs into defects in the distal metaphysis. Methods. 48 white laboratory rats (age 5–6 months) were used, which were randomly divided into groups: Control — 3D-I; Experiment-I — 3D-I, saturated MSCs; Experiment II — 3D-I, with injection of 0.1‒0.2 ml of medium with MSCs into the area of surgical intervention 7 days after implantation. 15, 30 and 90 days after the operation, histological (with histomorphometry) studies were conducted. Results. The area of 3D-I decreased with time in all groups and connective and bone tissues formed in different ratios. 15 days after the surgery, in the Experiment-I group, the area of the connective tissue was 1.9 and 1.6 times greater (p<0.001) in comparison to the Control and Experiment II; 30 days it was greater 1.6 times (p < 0.001) and 1.4 times (p=0.001), respectively. 30 days after the surgery, the area of newly formed bone in the Experiment-I group was 2.2 times (p < 0.001) less than in the Control. On the contrary, in the Experiment-II, the area of newly formed bone was 1.5 and 3.3 times greater (p < 0.001) compared to Experiment-I and Control, respectively. Conclusions. The studied 3D-I with time after their implantation into the metaphyseal defects of the rats’ femurs are replaced by connective and bone tissues. The use of 3D-I, saturated MSCs, 15 and 30 days after the surgery, caused excessive formation of connective tissue and slower bone formation. Local injection of MSCs 7 days after the implantation of 3D-I caused to the formation of a larger area of newly bone 30th day after surgery compared to 3D-I alone and 3D-I with MSCs.
References
- Kazmirchuk, A., Yarmoliuk, Y., Lurin, I., Gybalo, R., Burianov, O., Derkach, S., & Karpenko, K. (2022). Ukraine’s Experience with Management of Combat Casualties Using NATO’s Four-Tier “Changing as Needed” Healthcare System. World Journal of Surgery, 46(12), 2858–2862. https://doi.org/10.1007/s00268-022-06718-3
- Feltri, P., Solaro, L., Di Martino, A., Candrian, C., Errani, C., & Filardo, G. (2022). Union, complication, reintervention and failure rates of surgical techniques for large diaphyseal defects: a systematic review and meta-analysis. Scientific reports, 12(1), 9098. https://doi.org/10.1038/s41598-022-12140-5
- Baldwin, P., Li, D. J., Auston, D. A., Mir, H. S., Yoon, R. S., & Koval, K. J. (2019). Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery. Journal of orthopaedic trauma, 33(4), 203–213. https://doi.org/10.1097/BOT.0000000000001420
- Kobbe, P., Laubach, M., Hutmacher, D. W., Alabdulrahman, H., Sellei, R. M., & Hildebrand, F. (2020). Convergence of scaffold-guided bone regeneration and RIA bone grafting for the treatment of a critical-sized bone defect of the femoral shaft. European journal of medical research, 25(1), 70. https://doi.org/10.1186/s40001-020-00471-w.
- Brunello, G., Panda, S., Schiavon, L., Sivolella, S., Biasetto, L., & Del Fabbro, M. (2020). The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review. Materials (Basel, Switzerland), 13(7), 1500. https://doi.org/10.3390/ma13071500
- Morris, M. T., Tarpada, S. P., & Cho, W. (2018). Bone graft materials for posterolateral fusion made simple: a systematic review. European spine journal, 27(8), 1856–1867. https://doi.org/10.1007/s00586-018-5511-6
- Haugen, H. J., Lyngstadaas, S. P., Rossi, F., & Perale, G. (2019). Bone grafts: which is the ideal biomaterial? Journal of clinical periodontology, 46 Suppl 21, 92–102. https://doi.org/10.1111/jcpe.13058.
- Stark, J. R., Hsieh, J., & Waller, D. (2019). Bone graft substitutes in single- or double-level anterior cervical discectomy and fusion: A Systematic Review. Spine, 44(10), E618–E628. https://doi.org/10.1097/BRS.0000000000002925
- Chen Y., Lin J., & Yu, X. (2020). Role of mesenchymal stem cells in bone fracture repair and regeneration. Chapter 7. In Ahmed H. K. El-Hashash (Eds.) Mesenchymal Stem Cells in Human Health and Diseases (pp. 127 ‒ 143). Academic Press. https://doi.org/10.1016/B978-0-12-819713-4.00007-4
- Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G., & Morrison, S. J. (2014). Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell stem cell, 15(2), 154–168. https://doi.org/10.1016/j.stem.2014.06.008.
- Lin, H., Sohn, J., Shen, H., Langhans, M. T., & Tuan, R. S. (2019). Bone marrow mesenchymal stem cells: Aging and tissue engineering applications to enhance bone healing. Biomaterials, 203, 96–110. https://doi.org/10.1016/j.biomaterials.2018.06.026li
- Science and society. Experts warn against bans on 3D printing. (2013). Science (New York, N.Y.), 342(6157), 439.
- Brachet, A., Bełżek, A., Furtak, D., Geworgjan, Z., Tulej, D., Kulczycka, K., Karpiński, R., Maciejewski, M., & Baj, J. (2023). Application of 3D Printing in Bone Grafts. Cells, 12(6), 859. https://doi.org/10.3390/cells12060859
- Chen, H., Han, Q., Wang, C., Liu, Y., Chen, B., & Wang, J. (2020). Porous Scaffold Design for Additive Manufacturing in Orthopedics: A Review. Frontiers in bioengineering and biotechnology, 8, 609. https://doi.org/10.3389/fbioe.2020.00609
- Dall'Ava, L., Hothi, H., Henckel, J., Di Laura, A., Tirabosco, R., Eskelinen, A., Skinner, J., & Hart, A. (2021). Osseointegration of retrieved 3D-printed, off-the-shelf acetabular implants. Bone & joint research, 10(7), 388–400. https://doi.org/10.1302/2046-3758.107.BJR-2020-0462.R1
- Habibovic, P., Gbureck, U., Doillon, C. J., Bassett, D. C., van Blitterswijk, C. A., & Barralet, J. E. (2008). Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants. Biomaterials, 29(7), 944–953. https://doi.org/10.1016/j.biomaterials.2007.10.023
- Makarov, V., Dedukh, N., & Nikolchenko, O. (2021). Osteointegration of polylactide-basedimplants. Trauma, 22 (3), 58–62. https://doi.org/10.22141/1608-1706.3.22.2021.236325
- Hamad, K., Kaseem, M., Yang, H. W., Deri, F., & Ko, Y. G. (2015). Properties and medical applications of polylactic acid: A review. Express Polymer Letters, 9(5), 435-55. https://doi.org/110.3144/expresspolymlett.2015.42
- European Convention for the protection of vertebrate animals used for research and other scientific purposes. Strasbourg, 18 March 1986: official translation. Verkhovna Rada of Ukraine. (In Ukrainian). URL: http://zakon.rada.gov.ua/cgi-bin/laws/main.cgi?nreg=994_137. 21
- On protection of animals from cruel treatment: Law of Ukraine №3447-IV of February 21, 2006. The Verkhovna Rada ofUkraine. (In Ukrainian). URL: http://zakon.rada.gov.ua/cgi-bin/laws/main.cgi?nreg=3447-15
- Ashukinа, N. O., Vorontsov, P. M., Maltseva, V. Ye., Danуshchuk, Z. M., Nikolchenko, O. A., Samoylova, K. M., & Husak V. S. (2022). Morphology of the repair of critical size bone defects which filling allogeneic bone implants in combination with mesenchymal stem cells depending on the recipient age in the experiment. Orthopaedics, Traumatology and Prosthetics, (3‒4), 80‒90. http://dx.doi.org/10.15674/0030-598720223-480-90
- Gontar, N. M. (2023) Changes in markers of bone tissue remodeling and the inflammatory process in the blood serum of white rats in case of defect filling of the femur with implants based on polylactide and tricalciumphosphate with mesenchymal stem cells. Orthopaedics, Traumatology and Prosthetics (2), 33‒42. http://dx.doi.org/10.15674/0030-59872023233-42
- Walters, S. J., Campbell, M. J., & Machin, D. (2021). Medical Statistics: A Textbook for the Health Sciences (5th Eds). Wiley-Blackwellm
- Poser, L., Matthys, R., Schawalder, P., Pearce, S., Alini, M., & Zeiter, S. (2014). A standardized critical size defect model in normal and osteoporotic rats to evaluate bone tissue engineered constructs. BioMed research international, 2014, 348635. https://doi.org/10.1155/2014/348635
- Tao, Z. S., Wu, X. J., Zhou, W. S., Wu, X. J., Liao, W., Yang, M., Xu, H. G., & Yang, L. (2019). Local administration of aspirin with β-tricalcium phosphate/poly-lactic-co-glycolic acid (β-TCP/PLGA) could enhance osteoporotic bone regeneration. Journal of bone and mineral metabolism, 37(6), 1026–1035. https://doi.org/10.1007/s00774-019-01008-w
- Gentile, P., Chiono, V., Carmagnola, I., & Hatton, P. V. (2014). An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. International journal of molecular sciences, 15(3), 3640–3659. https://doi.org/10.3390/ijms15033640
- Xu, Z., Wang, N., Liu, P., Sun, Y., Wang, Y., Fei, F., Zhang, S., Zheng, J., & Han, B. (2019). Poly(Dopamine) Coating on 3D-Printed Poly-Lactic-Co-Glycolic Acid/β-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering. Molecules (Basel, Switzerland), 24(23), 4397. https://doi.org/10.3390/molecules24234397
- Zyman, Z. Z. (2018). Calcium-phosphate biomaterials. Textbook, Kharkiv. (in Ukrainian)
- Bohner, M., Santoni, B. L. G., & Dobelin, N. (2020). β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta biomaterialia, 113, 23–41. https://doi.org/10.1016/j.actbio.2020.06.022
- Mende, W., Götzl, R., Kubo, Y., Pufe, T., Ruhl, T., & Beier,J. P. (2021). The role of adipose stem cells in bone regeneration and bone tissue engineering. Cells, 10(5), 975. https://doi. org/10.3390/cells10050975
- Chatterjea, A., LaPointe, V. L., Alblas, J., Chatterjea, S., van Blitterswijk, C. A., & de Boer, J. (2014). Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats. Journal of cellular and molecular medicine, 18 (1), 134–142. https://doi.org/10.1111/jcmm.12172
- Grayson, W. L., Bunnell, B. A., Martin, E., Frazier, T., Hung, B. P., & Gimble, J. M. (2015). Stromal cells and stem cells in clinical bone regeneration. Nature reviews. Endocrinology, 11 (3), 140–150. https://doi.org/10.1038/nrendo.2014.234
- Wang, X., Jiang, H., Guo, L., Wang, S., Cheng, W., Wan, L., Zhang, Z., Xing, L., Zhou, Q., Yang, X., Han, H., Chen, X., & Wu, X. (2021). SDF-1 secreted by mesenchymal stem cells promotes the migration of endothelial progenitor cells via CXCR4/PI3K/AKT pathway. Journal of molecular histology, 52 (6), 1155–1164. https://doi.org/10.1007/s10735-021-10008-y
Downloads
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors retain the right of authorship of their manuscript and pass the journal the right of the first publication of this article, which automatically become available from the date of publication under the terms of Creative Commons Attribution License, which allows others to freely distribute the published manuscript with mandatory linking to authors of the original research and the first publication of this one in this journal.
Authors have the right to enter into a separate supplemental agreement on the additional non-exclusive distribution of manuscript in the form in which it was published by the journal (i.e. to put work in electronic storage of an institution or publish as a part of the book) while maintaining the reference to the first publication of the manuscript in this journal.
The editorial policy of the journal allows authors and encourages manuscript accommodation online (i.e. in storage of an institution or on the personal websites) as before submission of the manuscript to the editorial office, and during its editorial processing because it contributes to productive scientific discussion and positively affects the efficiency and dynamics of the published manuscript citation (see The Effect of Open Access).