Prefabrication in Microsurgery

Prefabrication is a reconstructive technique that establishes new vascular supply to tissue by transferring a vascular pedicle, making it especially valuable in complex cases with limited donor sites. The process occurs in 2 stages: first, the pedicle is implanted into target tissue to promote angiogenesis and arteriogenesis and second, after 4 to 8 weeks, the flap is elevated on its new blood supply. Prefabrication differs from prelamination, as it adds vasculature rather than layering tissues. Applications extend to skin, cartilage, bone, jejunum, capsules, and even synthetic matrices, though challenges like venous congestion may require additional surgical strategies.

Key points

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Prefabrication is a reconstructive technique that establishes neovascularization by transferring a vascular pedicle, enabling use in complex cases where donor sites are limited.
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Prefabrication relies mainly on angiogenesis (sprouting and intussusceptive) and arteriogenesis, with vascular endothelial growth factor and other growth factors driving new vessel formation.
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Prefabrication has been used for fasciocutaneous flaps, bone, cartilage, jejunum, capsule, and even synthetic materials (eg, bilaminate skin substitutes), broadening reconstructive options.
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Prefabricated flaps can suffer from venous congestion due to mismatched drainage patterns; solutions include additional vein anastomoses or flap delay techniques.
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Composite prefabrication and tissue expansion are additional strategies for reconstruction but carry more complexity.

Abbreviation

VEGF	vascular endothelial growth factor

Introduction

Prefabrication is the neovascularization of tissue through vessel transfer. Initially introduced in the 1970s, prefabrication is more often utilized in complex reconstructions where donor availability is severely compromised such as in patients with burns. ^,^,^,^,^,^,^,^,

The technique of prefabrication brings an axial blood supply to an area of tissue that is not supplied by an axial pedicle. This technique occurs in 2 stages. The first stage involves dissecting a vascular pedicle either isolated as the artery and vein alone or incorporated in a muscle, fascia, or bone ( Fig. 1 A–G ). The pedicle is then transposed to an adjacent or distant location. The overlying skin is closed and the pedicle allowed time to eventually vascularize the surrounding tissue through angiogenesis. The second stage of the procedure involves elevating the new axial flap on the pedicle. The second stage is performed approximately 4 to 8 weeks after the first stage procedure. ^, At this stage, the flap is completely supported by the neovascularization recently created.

A 7-panel photo series visually documents a staged facial reconstruction, from scarred tissue to final surgical repair using a vascularized tissue flap. — Fig. 1

Neovascularization can occur through 3 different pathways: vasculogenesis, angiogenesis, and arteriogenesis. ^, Vasculogenesis occurs during embryonic development through cell differentiation, growth factors and vessel maturation ultimately forming the vascular network. Angiogenesis is a process of new blood vessel formation from pre-existing vessels (postvenule capillaries) usually initiated from tissue environments subject to ischemia, hypoxia, inflammation, or nutrient deprivation. Arteriogenesis is a process of new vessel formation related to flow dynamics from pre-existing blood vessels (arterioles) initiated through tissue stress, shear, and tissue demand such as exercise. ^,

Prefabrication occurs through angiogenesis and arteriogenesis. There are 2 main types of angiogenesis: sprouting angiogenesis and intussusceptive angiogenesis ( Fig. 2 A, B ). The process of either type of angiogenesis is similar. The endothelial cells that line the arteries and veins are in a contiguous monolayer. The endothelial cells that line the capillaries, however, are somewhat fenestrated to permit cell preserving homeostatic nutrients to easily transfer in and out of the intravascular. ^, New vessel outgrowth is activated by growth factors predominantly, vascular endothelial growth factor (VEGF), released by local tissues from the insulting environment (ischemia, stress, and so forth noted earlier). The endothelial cells subsequently secrete matrix metalloproteinases to create fenestrations in the basement membrane, which permits activated endothelial cell migration through the vessel weakened windows. These immerging endothelial cells are called “tip cells,” which migrate toward to stressed environment like that created while dissecting tissue planes developed in the transfer of a blood vessel in. ^, The proliferating cells at the base of the sprouting vessel are called “stalk cells” and form a tubular extension of the native vessel. As tubular extensions migrate, convergence with other new tubules develop into vascular networks. Blood flow behind the leading cells fosters their migration and growth. The basement membrane develops and pericytes around the new vessels are recruited to form a mature vasculature.

A two-panel diagram. Panel A shows a side view with labeled pericyte, basement membrane, EC, stalk cell, and tip cell. Panel B shows a front view with labeled pericyte, EC, and basement membrane. — Fig. 2

Intussusceptive angiogenesis involves the longitudinal splitting of vessels into new vessels through the formation of transcapillary tissue pillars that form partition within the vessels to ultimately create microvascular growth and branching or arborization.

It is more likely that new vascularity seen with prefabrication is a result of sprouting angiogenesis rather than intussusceptive angiogenesis. As vascular networks sprout and arborize, the adjacent tissues are populated by the new vessels. Remodeling of the new vascular network soon becomes intwined in surrounding tissue types. The result is a new blood supply to tissues where the vascular pedicle had been transplanted.

Prefabrication is very different than prelamination. The technique of prelamination stacks different tissue types upon each other to create a composite tissue. For example, elevating a flap and placing a cartilage graft on the undersurface is a form of prelamination ( Fig. 3 A, B ). Prelamination involves tissue layering without the addition of a new vessel as is seen with prefabrication.

Two surgical images show a forehead flap procedure involving prelamination with a skin graft and post-operative closure. — Fig. 3

Originally, prefabrication was designed for creating axial blood flow to a fasciocutaneous skin paddle. The prefabricated flap could then be transposed to adjacent areas more reliably on the axial blood supply. The skin paddle could be expanded with a tissue expander before transfer by placing the blood vessel between the elevated skin paddle above and the tissue expander below ( Fig. 4 A–C ). After appropriate expansion, the flap is transferred on the prefabricated pedicle. A prefabricated flap can also be transferred as a free flap (see Fig. 4 D–H).

An 8-panel image series shows staged reconstruction of a scarred neck in a burn patient using expanded abdominal tissue. — Fig. 4

The time to reliable neovascularization may vary but typically it can occur within 4 weeks. A longer delay between the initial pedicle transfer to the new tissue (stage 1) and flap transfer (stage 2) can enhance neovascularization. ^, Introducing promotors of angiogenesis such as fibroblast growth factor or VEGF may also improve neovascularization and thus the flap’s survival, but this is not usually necessary. ^,^,

Prefabricated flaps are vulnerable to transient venous congestion because venous drainage may follow the random outflow rather than parallel to the axial vessels and the neoarterialization. It may be necessary to identify superficial veins for separate anastomosis at distant areas of the flap in order to prevent venous congestion in these areas. The venous congestion is a similar finding that one sees with tissue expenders where the expansion may capture new extended angiosomes but not necessarily the distant venosomes where the venous outflow is in a different direction than the main vein of the pedicle. Strategies to address such venous congestion are similar to those of other flap surgery where additional vein anastomoses may be needed. ^, Flap delay techniques may also enhance the venous drainage through the main pedicle.

Prefabricated cartilage, bone, jejunum, and capsule have also been investigated with encouraging results that have led to clinical applications. ^,^,^,^, Capsule is scar tissue that forms around various implants as a biological response to a foreign body. Transferring a vascular pedicle over an implant or tissue expander will be incorporated into the capsule and vascularize the capsule as well ( Fig. 5 A, B ). Other tissues can then be put into the capsule or the capsule alone can be transferred as a vascularized capsule flap. Cartilage is a good candidate to place within a capsule since cartilage will survive through diffusion rather than an integrated internal blood supply ( Fig. 6 A–H ). The limits of bone prefabrication have not been fully defined at this point ( Fig. 7 A–M ). Composite prefabricated flaps can be designed as well. These flaps would have different tissues incorporated either through the addition of prelamination or through neovascularization of the different tissues that are adjacent to each other. Composite tissue of skin and bowel prefabrication has been investigated where a deep inferior epigastric perforator flap has been successfully prefabricated on a segment of jejunum in an animal model.