= Solution
\b[New <blood vessels> in a healing wound arise chiefly by <angiogenesis>: sprouts grow from surviving <blood vessels>, unite into patent channels, and mature within the <granulation tissue>.] <Blood> does not simply excavate permanent channels in a shapeless clot.
The initial wound contains a provisional <extracellular matrix>, including <fibrin>, with inflammatory <biological cells> and later <fibroblasts>. Local <hypoxia> and signals from injured <tissue> and inflammatory <biological cells> stimulate surviving <endothelium>. In modern molecular terms, <vascular endothelial growth factor> is an important stimulus. This molecular account explains the process today; it is not evidence that the examiner expected the named signalling molecule in 1867.<Molecular Biology of the Cell, 4th edition>[Chapter 22, Blood Vessels and Endothelial Cells, Angiogenesis Is Controlled by Factors Released by the Surrounding Tissues; Figure 22-27]{ref}
The sequence is as follows:
* Portions of the old vascular <basement membrane> and surrounding <extracellular matrix> are remodelled. Activated <endothelium> <biological cells> extend and migrate towards the wound.
* <Endothelium> <cell proliferation> and <cell migration> lengthen the sprouts. Their organization establishes a lumen rather than a solid cord remaining indefinitely.
* Sprouts meet one another or an existing <blood vessel>, forming an <anastomosis>. A connected route with inflow and outflow can then carry <blood>. A blind sprout is not yet a useful circulating loop.
* Junctions between <endothelium> <biological cells>, a renewed <basement membrane>, and supporting <pericytes> stabilize the small <blood vessels>. Larger channels acquire further mural support as appropriate.
* During remodelling, many surplus <capillaries> regress. The vascular, red <granulation tissue> becomes a less vascular mature scar.
This sequence separates growth of the cellular lining, formation of the channel, establishment of flow, and stabilization. These are different experimental observations, even though they overlap in time.<Angiogenesis in Inflammation and the Microcirculation>[Chapter 6, initiation by endothelial activation, matrix degradation, migration, proliferation and maturation]{ref}
An instructive anatomical investigation follows the wound at successive stages. Thin sections show solid sprouts, lumina lined by <endothelium> and their relation to the old <blood vessels>. Injection of a suitable casting material into the supplying <blood vessels>, followed by examination of the cast, reveals which channels are continuous with the circulation. The corneal wound example in the modern textbook uses resin injection and <scanning electron microscopy> of the resulting casts. Seeing an cord of <endothelium> and demonstrating a perfused loop therefore answer different questions.<Molecular Biology of the Cell, 4th edition>[Chapter 22, Blood Vessels and Endothelial Cells, Figure 22-27 caption, vascular casts after corneal wounding]{ref}
\b[The essential repair process is sprouting, lumen formation, connection and maturation.] The contrast with embryonic <vasculogenesis>, assembly from vascular precursors, helps define <angiogenesis>; it does not require assuming that every new <blood vessel> in an adult wound has an identical cellular history.
Back to article page