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DOI: 10.1055/s-0042-1757182
The Future of Microsurgery: Vascularized Composite Allotransplantation and Engineering Vascularized Tissue
Funding None.Abstract
Background Microsurgical techniques have revolutionized the field of reconstructive surgery and are the mainstay for complex soft tissue reconstruction. However, their limitations have promoted the development of viable alternatives. This article seeks to explore technologies that have the potential of revolutionizing microsurgical reconstruction as it is currently known, reflect on current and future vascularized composite allotransplantation (VCA) practices, as well as describe the basic science within emerging technologies and their potential translational applications.
Methods A literature review was performed of the technologies that may represent the future of microsurgery: vascularized tissue engineering (VCA) and flap-specific tissue engineering.
Results VCA has shown great promise and has already been employed in the clinical setting (especially in face and limb transplantation). Immunosuppression, logistics, cost, and regulatory pathways remain barriers to overcome to make it freely available. Vascularized and flap-specific tissue engineering remain a laboratory reality but have the potential to supersede VCA. The capability of creating an off-the-shelf free flap matching the required tissue, size, and shape is a significant advantage. However, these technologies are still at the early stage and require significant advancement before they can be translated into the clinical setting.
Conclusion VCA, vascularized tissue engineering, and flap-specific bioengineering represent possible avenues for the evolution of current microsurgical techniques. The next decade will elucidate which of these three strategies will evolve into a tangible translational option and hopefully bring a paradigm shift of reconstructive surgery.
Keywords
vascularized composite allotransplantation - composite tissue transplantation - tissue engineeringAuthors' Contributions
FME, BKS, JDF, and RS performed the literature review and drafted the manuscript. JPR, KGM, and MGS provided direction, edits, and critical commentary on the manuscript and its content throughout the course of it being drafted.
Data Availability
The data presented in this study are available on request from the corresponding author.
Publication History
Article published online:
14 October 2022
© 2022. Society of Indian Hand Surgery & Microsurgeons. All rights reserved.
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References
- 1 Dubernard JM, Owen E, Herzberg G. et al. Human hand allograft: report on first 6 months. Lancet 1999; 353 (9161): 1315-1320 DOI: 10.1016/S0140-6736(99)02062-0.
- 2 Jones JW, Gruber SA, Barker JH, Breidenbach WC. Louisville Hand Transplant Team. Successful hand transplantation. One-year follow-up. N Engl J Med 2000; 343 (07) 468-473 DOI: 10.1056/NEJM200008173430704.
- 3 Kaufman CL, Bhutiani N, Ramirez A. et al. Currents of vascularized composite allotransplantation. Am Surg 2019; 85 (06) 631-637 DOI: 10.1177/000313481908500628.
- 4 Cetrulo Jr CL, Ng ZY, Winograd JM, Eberlin KR. The advent of vascularized composite allotransplantation. Clin Plast Surg 2017; 44 (02) 425-429 DOI: 10.1016/j.cps.2016.12.007.
- 5 Girard AO, Lake IV, Lopez CD. et al. Vascularized composite allotransplantation of the penis: current status and future perspectives. International Journal of Impotence Research 2022; 34: 383-391
- 6 Petruzzo P, Kanitakis J, Badet L. et al. Long-term follow-up in composite tissue allotransplantation: in-depth study of five (hand and face) recipients. Am J Transplant 2011; 11 (04) 808-816 DOI: 10.1111/j.1600-6143.2011.03469.x.
- 7 Murray JE. Organ transplantation (skin, kidney, heart) and the plastic surgeon. Plast Reconstr Surg 1971; 47 (05) 425-431
- 8 Mathes DW, Randolph MA, Solari MG. et al. Split tolerance to a composite tissue allograft in a swine model. Transplantation 2003; 75 (01) 25-31 DOI: 10.1097/01.TP.0000035881.03116.E3.
- 9 Petruzzo P, Lanzetta M, Dubernard JM. et al. The International Registry on Hand and Composite Tissue Transplantation. Transplantation 2010; 90 (12) 1590-1594 DOI: 10.1097/TP.0b013e3181ff1472.
- 10 Kawai T, Cosimi AB, Spitzer TR. et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008; 358 (04) 353-361 DOI: 10.1056/NEJMoa071074.
- 11 Kawai T, Sachs DH, Sykes M, Cosimi AB. Immune Tolerance Network. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2013; 368 (19) 1850-1852 DOI: 10.1056/NEJMc1213779.
- 12 Leonard DA, Kurtz JM, Mallard C. et al. Vascularized composite allograft tolerance across MHC barriers in a large animal model. Am J Transplant 2014; 14 (02) 343-355 DOI: 10.1111/ajt.12560.
- 13 Chang SY, Huang JJ, Tsao CK. et al. Does ischemia time affect the outcome of free fibula flaps for head and neck reconstruction? A review of 116 cases. Plast Reconstr Surg 2010; 126 (06) 1988-1995 DOI: 10.1097/PRS.0b013e3181f448c8.
- 14 Gürlek A, Kroll SS, Schusterman MA. Ischemic time and free flap success. Ann Plast Surg 1997; 38 (05) 503-505
- 15 Wagh M, Pantazi G, Romeo R, Hurley JV, Morrison WA, Knight KR. Cold storage of rat skeletal muscle free flaps and pre-ischemic perfusion with modified UW solution. Microsurgery 2000; 20 (07) 343-349 DOI: 10.1002/1098-2752(2000)20:7<343:aid-micr6>3.0.co;2-c.
- 16 Taeger CD, Friedrich O, Dragu A. et al. Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time. Sci Rep 2015; 5: 11956-11956 DOI: 10.1038/srep11956.
- 17 Slater NJ, Zegers HJH, Küsters B, Beune T, van Swieten HA, Ulrich DJO. Ex-vivo oxygenated perfusion of free flaps during ischemia time: a feasibility study in a porcine model and preliminary results. J Surg Res 2016; 205 (02) 292-295 DOI: 10.1016/j.jss.2016.06.096.
- 18 Taeger CD, Friedrich O, Horch RE. et al. Tissue viability of free flaps after extracorporeal perfusion using a modified hydroxyethyl starch solution. J Clin Med 2020; 9 (12) E3929 DOI: 10.3390/jcm9123929.
- 19 Wolff KD. New aspects in free flap surgery: mini-perforator flaps and extracorporeal flap perfusion. J Stomatol Oral Maxillofac Surg 2017; 118 (04) 238-241 DOI: 10.1016/j.jormas.2017.06.004.
- 20 Fichter AM, Ritschl LM, Rau A. et al. Free flap rescue using an extracorporeal perfusion device. J Craniomaxillofac Surg 2016; 44 (12) 1889-1895 DOI: 10.1016/j.jcms.2016.09.010.
- 21 Siemionow M, Gatherwright J, Djohan R, Papay F. Cost analysis of conventional facial reconstruction procedures followed by face transplantation. Am J Transplant 2011; 11 (02) 379-385 DOI: 10.1111/j.1600-6143.2010.03373.x.
- 22 Chung KC, Oda T, Saddawi-Konefka D, Shauver MJ. An economic analysis of hand transplantation in the United States. Plast Reconstr Surg 2010; 125 (02) 589-598 DOI: 10.1097/PRS.0b013e3181c82eb6.
- 23 Caterson EJ, Nesti LJ, Albert T, Danielson K, Tuan R. Application of mesenchymal stem cells in the regeneration of musculoskeletal tissues. MedGenMed 2001; E1
- 24 Lu P, Takai K, Weaver VM, Werb Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 2011; 3 (12) a005058 DOI: 10.1101/cshperspect.a005058.
- 25 Gelse K, Pöschl E, Aigner T. Collagens–structure, function, and biosynthesis. Adv Drug Deliv Rev 2003; 55 (12) 1531-1546
- 26 Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci 2010; 123 (Pt 24): 4195-4200 DOI: 10.1242/jcs.023820.
- 27 Kim SH, Turnbull J, Guimond S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol 2011; 209 (02) 139-151 DOI: 10.1530/JOE-10-0377.
- 28 Kresse H, Schönherr E. Proteoglycans of the extracellular matrix and growth control. J Cell Physiol 2001; 189 (03) 266-274 DOI: 10.1002/jcp.10030.
- 29 Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science 2009; 324 (5935): 1673-1677 DOI: 10.1126/science.1171643.
- 30 Cooper DK, Gollackner B, Sachs DH. Will the pig solve the transplantation backlog?. Annu Rev Med 2002; 53: 133-147 DOI: 10.1146/annurev.med.53.082901.103900.
- 31 Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials 2011; 32 (12) 3233-3243 DOI: 10.1016/j.biomaterials.2011.01.057.
- 32 Guyette JP, Gilpin SE, Charest JM, Tapias LF, Ren X, Ott HC. Perfusion decellularization of whole organs. Nat Protoc 2014; 9 (06) 1451-1468 DOI: 10.1038/nprot.2014.097.
- 33 Seetapun D, Ross JJ. Eliminating the organ transplant waiting list: the future with perfusion decellularized organs. Surgery 2017; 161 (06) 1474-1478 DOI: 10.1016/j.surg.2016.09.041.
- 34 Zhang Q, Johnson JA, Dunne LW. et al. Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps. Acta Biomater 2016; 35: 166-184 DOI: 10.1016/j.actbio.2016.02.017.
- 35 Gilbert TW. Strategies for tissue and organ decellularization. J Cell Biochem 2012; 113 (07) 2217-2222 DOI: 10.1002/jcb.24130.
- 36 Gilpin A, Yang Y. Decellularization strategies for regenerative medicine: from processing techniques to applications. BioMed Res Int 2017; 2017: 9831534 DOI: 10.1155/2017/9831534.
- 37 He M, Callanan A. Comparison of methods for whole-organ decellularization in tissue engineering of bioartificial organs. Tissue Eng Part B Rev 2013; 19 (03) 194-208 DOI: 10.1089/ten.TEB.2012.0340.
- 38 Hodde J, Janis A, Hiles M. Effects of sterilization on an extracellular matrix scaffold: part II. Bioactivity and matrix interaction. J Mater Sci Mater Med 2007; 18 (04) 545-550 DOI: 10.1007/s10856-007-2301-9.
- 39 Lee JH, Chang CH, Seo SW, Kim JK. The effects of sterilization methods on lyophilized cartilage grafts in an experimental model. J Craniofac Surg 2013; 24 (04) 1436-1440 DOI: 10.1097/SCS.0b013e31829025ab.
- 40 Ikada Y. Challenges in tissue engineering. J R Soc Interface 2006; 3 (10) 589-601 DOI: 10.1098/rsif.2006.0124.
- 41 Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med 1997; 3 (03) 282-286
- 42 Poornejad N, Buckmiller E, Schaumann L. et al. Re-epithelialization of whole porcine kidneys with renal epithelial cells. J Tissue Eng 2017; 8: 2041731417718809 DOI: 10.1177/2041731417718809.
- 43 Robertson MJ, Dries-Devlin JL, Kren SM, Burchfield JS, Taylor DA. Optimizing recellularization of whole decellularized heart extracellular matrix. PLoS One 2014; 9 (02) e90406 DOI: 10.1371/journal.pone.0090406.
- 44 Lu TY, Lin B, Kim J. et al. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun 2013; 4: 2307 DOI: 10.1038/ncomms3307.
- 45 Jank BJ, Goverman J, Guyette JP. et al. Creation of a bioengineered skin flap scaffold with a perfusable vascular pedicle. Tissue Eng Part A 2017; 23 (13-14): 696-707 DOI: 10.1089/ten.TEA.2016.0487.
- 46 Qu J, Van Hogezand RM, Zhao C, Kuo BJ, Carlsen BT. Decellularization of a fasciocutaneous flap for use as a perfusable scaffold. Ann Plast Surg 2015; 75 (01) 112-116 DOI: 10.1097/SAP.0000000000000157.
- 47 Shandalov Y, Egozi D, Koffler J. et al. An engineered muscle flap for reconstruction of large soft tissue defects. Proc Natl Acad Sci U S A 2014; 111 (16) 6010-6015 DOI: 10.1073/pnas.1402679111.
- 48 Guyette JP, Charest JM, Mills RW. et al. Bioengineering human myocardium on native extracellular matrix. Circ Res 2016; 118 (01) 56-72 DOI: 10.1161/CIRCRESAHA.115.306874.
- 49 Song JJ, Kim SS, Liu Z. et al. Enhanced in vivo function of bioartificial lungs in rats. Ann Thorac Surg 2011; 92 (03) 998-1005 , discussion 1005–1006 DOI: 10.1016/j.athoracsur.2011.05.018.
- 50 Yoon AP, Jones NF. Critical time for neovascularization/angiogenesis to allow free flap survival after delayed postoperative anastomotic compromise without surgical intervention: a review of the literature. Microsurgery 2016; 36 (07) 604-612 DOI: 10.1002/micr.30082.
- 51 Kroll SS, Schusterman MA, Reece GP. et al. Timing of pedicle thrombosis and flap loss after free-tissue transfer. Plast Reconstr Surg 1996; 98 (07) 1230-1233
- 52 Bui DT, Cordeiro PG, Hu QY, Disa JJ, Pusic A, Mehrara BJ. Free flap reexploration: indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg 2007; 119 (07) 2092-2100 DOI: 10.1097/01.prs.0000260598.24376.e1.
- 53 Wang J, Wei Y, Zhao S. et al. The analysis of viability for mammalian cells treated at different temperatures and its application in cell shipment. PLoS One 2017; 12 (04) e0176120 DOI: 10.1371/journal.pone.0176120.
- 54 Folkman J, Haudenschild CC, Zetter BR. Long-term culture of capillary endothelial cells. Proc Natl Acad Sci U S A 1979; 76 (10) 5217-5221
- 55 Nerem RM, Levesque MJ, Cornhill JF. Vascular endothelial morphology as an indicator of the pattern of blood flow. J Biomech Eng 1981; 103 (03) 172-176
- 56 Hubbell JA, Massia SP, Desai NP, Drumheller PD. Endothelial cell-selective materials for tissue engineering in the vascular graft via a new receptor. Biotechnology (N Y) 1991; 9 (06) 568-572
- 57 Tork S, Jefferson RC, Janis JE. Acellular dermal matrices: applications in plastic surgery. Semin Plast Surg 2019; 33 (03) 173-184 DOI: 10.1055/s-0039-1693019.
- 58 Gravina PR, Pettit RW, Davis MJ, Winocour SJ, Selber JC. Evidence for the use of acellular dermal matrix in implant-based breast reconstruction. Semin Plast Surg 2019; 33 (04) 229-235 DOI: 10.1055/s-0039-1696986.
- 59 Henning JA, Liette MD, Laklouk M, Fadel M, Masadeh S. The role of dermal regenerative templates in complex lower extremity wounds. Clin Podiatr Med Surg 2020; 37 (04) 803-820 DOI: 10.1016/j.cpm.2020.07.010.
- 60 Jordan SW, Khavanin N, Fine NA, Kim JYS. An algorithmic approach for selective acellular dermal matrix use in immediate two-stage breast reconstruction: indications and outcomes. Plast Reconstr Surg 2014; 134 (02) 178-188 DOI: 10.1097/prs.0000000000000366.
- 61 Shakir S, Messa IV CAI, Broach RB. et al. Indications and limitations of bilayer wound matrix-based lower extremity reconstruction: a multidisciplinary case-control study of 191 wounds. Plast Reconstr Surg 2020; 145 (03) 813-822 DOI: 10.1097/prs.0000000000006609.
- 62 Unger RE, Sartoris A, Peters K. et al. Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials. Biomaterials 2007; 28 (27) 3965-3976 DOI: 10.1016/j.biomaterials.2007.05.032.
- 63 Niklason LE, Gao J, Abbott WM. et al. Functional arteries grown in vitro. Science 1999; 284 (5413): 489-493
- 64 Dahl SL, Rhim C, Song YC, Niklason LE. Mechanical properties and compositions of tissue engineered and native arteries. Ann Biomed Eng 2007; 35 (03) 348-355 DOI: 10.1007/s10439-006-9226-1.
- 65 Dahl SL, Vaughn ME, Niklason LE. An ultrastructural analysis of collagen in tissue engineered arteries. Ann Biomed Eng 2007; 35 (10) 1749-1755 DOI: 10.1007/s10439-007-9340-8.
- 66 Gentile C, Fleming PA, Mironov V, Argraves KM, Argraves WS, Drake CJ. VEGF-mediated fusion in the generation of uniluminal vascular spheroids. Dev Dyn 2008; 237 (10) 2918-2925 DOI: 10.1002/dvdy.21720.
- 67 Xu H, Deshmukh R, Timmons R, Nguyen KT. Enhanced endothelialization on surface modified poly(L-lactic acid) substrates. Tissue Eng Part A 2011; 17 (5-6): 865-876 DOI: 10.1089/ten.TEA.2010.0129.
- 68 Wang H, Yin Y, Li W. et al. Over-expression of PDGFR-β promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway. PLoS One 2012; 7 (02) e30503 DOI: 10.1371/journal.pone.0030503.
- 69 Ren X, Feng Y, Guo J. et al. Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications. Chem Soc Rev 2015; 44 (15) 5680-5742 DOI: 10.1039/c4cs00483c.
- 70 Caglayan E, Vantler M, Leppänen O. et al. Disruption of platelet-derived growth factor-dependent phosphatidylinositol 3-kinase and phospholipase Cγ 1 activity abolishes vascular smooth muscle cell proliferation and migration and attenuates neointima formation in vivo. J Am Coll Cardiol 2011; 57 (25) 2527-2538 DOI: 10.1016/j.jacc.2011.02.037.
- 71 Shandalov Y, Egozi D, Freiman A, Rosenfeld D, Levenberg S. A method for constructing vascularized muscle flap. Methods 2015; 84: 70-75 DOI: 10.1016/j.ymeth.2015.03.021.
- 72 Freiman A, Shandalov Y, Rosenfeld D. et al. Engineering vascularized flaps using adipose-derived microvascular endothelial cells and mesenchymal stem cells. J Tissue Eng Regen Med 2018; 12: e130-e141
- 73 Freiman A, Shandalov Y, Rozenfeld D. et al. Adipose-derived endothelial and mesenchymal stem cells enhance vascular network formation on three-dimensional constructs in vitro. Stem Cell Res Ther 2016; 7: 5 DOI: 10.1186/s13287-015-0251-6.
- 74 Antunes MB, Chalian AA. Microvascular Reconstruction of Nasal Defects. Facial Plastic Surgery Clinics of North America 2011; 19 (01) 157-162
- 75 Taghinia AH, Pribaz JJ. Complex nasal reconstruction. Plast Reconstr Surg 2008; 121 (02) 15e-27e DOI: 10.1097/01.prs.0000298113.56554.c3.
- 76 Chim H, Amer H, Mardini S, Moran SL. Vascularized composite allotransplant in the realm of regenerative plastic surgery. Mayo Clin Proc 2014; 89 (07) 1009-1020 DOI: 10.1016/j.mayocp.2014.05.009.
- 77 Wo L, Bueno E, Pomahac B. Facial transplantation: worth the risks? A look at evolution of indications over the last decade. Curr Opin Organ Transplant 2015; 20 (06) 615-620 DOI: 10.1097/mot.0000000000000253.
- 78 Rahmel A. Vascularized composite allografts: procurement, allocation, and implementation. Curr Transplant Rep 2014; 1 (03) 173-182 DOI: 10.1007/s40472-014-0025-6.
- 79 Chandraker A, Arscott R, Murphy GF. et al. The management of antibody-mediated rejection in the first presensitized recipient of a full-face allotransplant. Am J Transplant 2014; 14 (06) 1446-1452 DOI: 10.1111/ajt.12715.
- 80 Weissenbacher A, Hautz T, Pratschke J, Schneeberger S. Vascularized composite allografts and solid organ transplants: similarities and differences. Curr Opin Organ Transplant 2013; 18 (06) 640-644 DOI: 10.1097/MOT.0000000000000019.
- 81 Services DoHaH. . Final rule. Federal Register. . In: Government TDJotUS. , ed. 7/3: 40033-40034–40042 2013