Faculty Bibliography

Synthesis of extracellular matrix by dermal fibroblasts is an important component of cutaneous wound repair. Scar remodeling and maturation is generally seen as the result of a fibroblast-regulated equilibrium between production and degradation of specific matrix constituents. Fibroblasts from normal dermis, reparative granulation tissue and mature scars were compared in vitro in terms of their ability to produce extracellular glycosaminoglycans (GAGs). All cell lines secreted dermatan sulfate (DS) and chondroitin sulfate (CS) into the culture medium. Hyaluronate (HA) was detected in medium from mature granulation tissue and scar cells, but little or none was found in medium from early granulation tissue or skin cells. In medium from normal skin fibroblasts, an unusual GAG was identified as a potential variant of DS on the basis of co-migration with HA but susceptibility to digestion with chondroitinase ABC. Heparan sulfate (HS) was the major pericellular GAG of all cultures except the mature scar cells, which contained a predominance of DS. A second pericellular GAG was identified as CS in mature granulation tissue cells, scar cells and skin cells; while HA was identified in the pericellular matrix of early granulation tissue cells. In addition, fibroblasts from both skin and early granulation tissue contained a GAG believed to be a variant of CS. These differences in GAG synthesis/secretion between cells maintained under identical culturing conditions could indicate either that distinct fibroblastic substrains exist during different stages of healing or that influences present during the healing process induce stable phenotypic alterations that are maintained through explant culturing and subsequent subcultivation

Fibroblast cultures derived from uninjured and reparative rabbit buccal mucosa were compared in terms of extracellular glycosaminoglycan (GAG) content and cellular response to interleukin-1 (IL-1). Under identical growth conditions, proliferation of both cell lines was the same. Both lines incorporated [3H]-glucosamine into GAG in cellular, pericellular, and medium fractions, with the majority of incorporated label residing in the medium. Dermatan sulfate (DS) was the predominant GAG in the medium fraction of both normal and wound fibroblast cultures; however, the two cell lines differed in the identity of the medium fraction's secondary GAG: chondroitin sulfate (CS) for normal fibroblasts and hyaluronic acid (HA) for wound-derived cells. The GAG content of the pericellular matrix for all cultures was the same regardless of the tissue of origin: heparan sulfate (HS) accompanied by a very small amount of CS. Exposure to IL-1 produced limited but highly specific effects: It was not mitogenic for either cell line but did cause a quantitative change (increase) in overall incorporation into GAG for medium and pericellular fractions for both cell lines. Further, IL-1 induced a qualitative change in GAG composition for normal mucosal fibroblastic medium fractions by causing the synthesis/release of heparan sulfate (HS) and a variant form of DS. These data support the hypothesis that different fibroblastic substrains can populate a given oral site as a function of variables such as injury and/or healing status

Both clinical and empirical evidence suggests that the 'normal' temporomandibular joint produces noise during function. The purpose of this study was to determine the conditions under which these noises might arise. Joint sounds and mandibular movements were recorded simultaneously from 200 adults who had no previous history or present symptoms of TMJ pain or dysfunction. The joint sounds were recorded bilaterally by means of two separate miniature vibration transducers mounted on a common headband, and incisal point mandibular movements were measured by a magnetometer tracking system. Recordings were made while each subject opened and closed the mouth, first in a natural and comfortable manner, and then to maximum displacement. Two types of measurements were made: the appearance, onset, and duration of joint-propagated sounds in relation to relative mandibular position; and the spectral properties of the detected sounds. The results of this study showed that for natural opening and closing movements of the mandible, the 'normal' TMJ was silent for all age groups. However, for the maximum displacement condition, detectable sounds appeared at the points of maximum displacement in both the opening and closing phases of the cycle in over 80 percent of the subjects. However, these sounds were, as a class, substantially longer than, and spectrally distinct from, abnormal joint sounds, suggesting that they arise from a distinct physical substrate

This report describes the healing of cutaneous wounds in experimental animals grafted with collagen-glycosaminoglycan (GAG) matrix/Silastic (Dow Corning Corp., Midland, MI) bilayers; assesses the feasibility of using collagen-GAG matrix as a vehicle for delivering culture-selected, autogenous fibroblasts to cutaneous wound sites; and evaluates the use of collagen-GAG/Silastic bilayers as mucosal substitutes. Cutaneous and mucosal wounds in New Zealand white rabbits were grafted with either acellular collagen-GAG/Silastic membrane or collagen-GAG/Silastic membrane previously seeded with cultured autogenous fibroblasts. Over 63 days, wound sites were analyzed at intervals based on wound contraction and histology. Cutaneous wound successfully incorporated grafted collagen-GAG matrix and were significantly inhibited in their rate and extent of wound contraction. Seeding membrane matrices with autogenous, cultured fibroblasts before grafting caused a marked increase in cellularity that persisted throughout the postgraft period. In mucosa, matrices were exteriorized rather than incorporated. This work suggests that collagen-GAG/Silastic bilayer may have value as a dermal substitute and, more significantly, may be appropriate as a vehicle for delivering culture-selected fibroblasts to cutaneous wound sites