Wound Healing and Collagen Formation

Abstract

The changes in scorbutic wounds following the administration of ascorbic acid have been investigated using the techniques of electron microscopy, histochemistry, and autoradioggraphy. Particular attention has been paid to the changes seen in the endoplasmic reticulum of the fibroblasts and to the identity of the extracellular filamentous material characteristic of scorbutic wounds. Seven-day-old wounds in scorbutic guinea pigs were examined prior to and from one to 72 hours following the administration of vitamin C. Fibroblasts from wounds of normal animals demonstrate a characteristic configuration of the ribosomes of the endoplasmic reticulum which is suggested to be analogous to polyribosomes described in cells synthesizing protein such as the reticulocyte. Tangential views of the membranes of the ergastoplasm show the ribosomes to be grouped in paired rows which take both straight and curved paths. This configuration is lost in scurvy and can be seen to begin to reappear as early as 4 hours after giving ascorbic acid. With increasing time, the morphology of the ribosomal aggregates approximates that seen in normal cells, so that by 24 hours their reorientation is complete. It is suggested that one of the disturbances in scurvy may relate to an alteration either in messenger RNA, in the ability of the ribosomes to relate to the messenger, or in the membranes of the ergastoplasm. In addition, the lack of formation of hydroxyamino acids necessary for completing collagen synthesis may be related to the architecture of the ribosomal aggregates. Extracellular collagen fibrils appear concomitant with the restoration of ribosomal and ergastoplasmic morphology as early as 12 hours after administration of ascorbic acid, with complete disappearance of the scorbutic extracellular material within 24 hours. Observations of this scorbutic material do not support the concept that it is a collagen precursor.

Influence of ascorbic acid on ribosomal patterns and collagen biosynthesis in healing wounds of scorbutic guinea pigs

“…A small but significant amount of underhydroxylated collagen has been found in connective tissue from scorbutic guinea pigs, and the results are consistent with the suggestion that scurvy produces an intracellular accumulation of severely underhydroxylated collagen which may after a time inhibit further synthesis of protocollagen (Barnes et al, 1970). Such a build-up might give rise to the distortion of the endoplasmic reticulum and changes in ribosomal patterns seen in electronmicroscopic studies of scorbutic guinea-pig wounds (Ross & Benditt, 1964). However, these disturbances of the cellular apparatus for protein synthesis are rapidly restored to the normal conformation when ascorbic acid is administered to the scorbutic animal and a concomitant appearance of extracellular collagen fibres is observed in the wound tissue (Ross & Benditt, 1964).…”

Wound healing in normal and diabetic Chinese hamsters

“…The appearance of the fibroblasts concomitant with the decrease in collagen in diabetic wounds suggested that the fibroblasts were not responding to injury as observed in control hamsters, but instead were undergoing progressive degeneration. This has been confirmed in other studies where the fibroblast was compromised and unable to synthesise collagen [23][24][25] and from reports examining the activity of fibroblasts in vitro from diabetic patients [26]. In every instance there was a n impaired response to injury with decreased collagen synthesis in vivo and in vitro and shorter life span in vitro [27].…”

Wound Healing and Collagen Formation

“…14). These sites were pointed out also in an earlier study of wounds (21), as well as by Karrer (28) in studies of the developing chick embryo aorta. Although frequent, these areas are not seen in every cell in each micrograph.…”

“…4 and 5). Ribosomes appeared to be labeled in regions where tangential sections of the membranes of the ergastoplasm demonstrate the characteristic aggregates of ribosomes (21) (Figs. 5 and 6).…”