Connective Tissue Healing Research Articles

Collagen types I and III at the implant/tissue interface

Collagen composition in tissue capsules around implants has been reported to differ histologically from collagen in subcutaneous connective tissue. In the present study, an immune histochemical analysis of collagen types I and III was undertaken in tissue capsules of various implant materials. The materials included polyvinyl chloride/polyacrylonitrile copolymer, poly(ethylene terephthalate), polysiloxane, titanium, and hydroxyapatite, which had been implanted into the dorsal subcutaneous space of rabbits for various time periods from 28 and to 90 days. The results indicate that collagen type III stained in all capsules independent of the evaluated materials, implantation periods, and material surface roughness. Collagen type I stained only in titanium implant capsules and dominated there over collagen type III. The staining sensitivity was highly specific and reproducible. The presence of collagen type III can be expected because it is the collagen of connective tissue healing. Collagen type I appears to be a response to chemical or electrochemical titanium surface properties but not to surface roughness. The quantitative relationship between the two collagen types may indicate capsule tissue stability and therefore serve as another biocompatibility measure.

Epidermal growth factor accelerates connective tissue wound healing in the perforated rat mesentery.

Epidermal growth factor (EGF) has been reported to stimulate healing of wounds in skin, cornea, and gastric mucosa. In the present study, we further investigate the effect of endogenous and exogenous EGF in healing of connective tissue wounds using the rat perforated mesentery model. Healing of mesenteric perforations is accomplished by the connective tissue fibroblasts since there are no interfering variables such as interactions of epithelial cells, desiccation, or foreign materials such as sutures or subcutaneous implants. We performed laparotomy in 114 adult male Sprague-Dawley rats and made 20 standardized perforations in the mesentery of each rat with a scalpel. Rats were randomly assigned to five groups. Group I received no treatment after surgery; Group II received intraperitoneal injections of phosphate-buffered saline (PBS) after surgery and then twice daily for the following 3 days; Group III received 10 micrograms of EGF in the PBS injections according to the same regimen as Group II; Group IV had sham exploration of the submandibular salivary glands; and Group V animals had excision of the submandibular glands 3 days before laparotomy to deprive the main source of EGF in rat. On Days 4 through 10 after surgery rats were sacrificed and the percentage of perforations in each rat which were closed was determined. The curves for the time course of wound closure for Groups IV and V were not different indicating that endogenous submandibular EGF does not play a role in healing of mesenteric wounds.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of connective tissue in inhibiting epithelial downgrowth on titanium-coated percutaneous implants.

Ideally, the surface of epithelium-penetrating implants should impede apical epithelial migration. Previous studies have shown that micromachined grooved surfaces can produce connective-tissue ingrowth, which inhibits epithelial downgrowth on percutaneous implants [Chehroudi et al., J. Biomed. Mater. Res., 24, 9, (1990)]. However, in those studies, connective tissue and epithelium interacted with the same surface so that the effects of the surfaces on each population could not be determined separately. The objectives of this study were (a) to examine cell behavior on implants in which connective tissue contacted surfaces of various topographies and epithelium encountered only a smooth surface, and (b) to compare one-stage and two-stage surgical techniques. Implants had a base component (BC) which was either smooth or had a surface with 19-micron- or 30-micron-deep grooves or 120-micron-deep tapered pits, and a skin-penetrating component (SPC) which was smooth. In the two-stage technique, the BC was implanted subcutaneously for 8 weeks, which permitted the healing of the peri-implant connective tissue. In the second stage the SPC was connected to the BC. For one-stage implants, BC & SPC were connected and implanted percutaneously. Implants (BC & SPC) were removed 1, 2, or 3 weeks after percutaneous implantation and histological sections were measured for recession, connective tissue and epithelial attachment as well as capsule thickness. Light microscopy indicated that both grooved and tapered pitted surfaces encouraged connective tissue ingrowth. On the grooved surfaces, the orientation of fibroblasts changed from an oblique to a more complex pattern which included cells having round nuclei within the grooves, as well as cells oriented oblique or perpendicular to the grooves. In the tapered pits a hammock-like arrangement of fibroblasts was observed. In some cases, foci of mineralization and formation of bonelike tissue were found on the grooved and pitted surfaces. The apical migration of the epithelium was significantly (p less than 0.05) inhibited by those micromachined surfaces which produced connective tissue ingrowth to the BC. This study found that placing the implants in two stages improved the performance of percutaneous devices, and that a further improvement was achieved if the implant had a surface promoting connective tissue ingrowth.

Electron Microscopical Evaluation of Connective Tissue Healing to Periodontally Involved Teeth

The present study was undertaken to examine if our novel root treatment for human periodontally involved teeth can facilitate a new connective tissue attachment. The novel treatment was in two parts: 1) planning and surface decalcification with citric acid on the coronal quarter of the exposed root corresponding to pocket, and 2) curettage of superficial cementum of the apical three quarters of the exposed root. The interface of the root surface and regenerating connective tissue was observed 2 and 3 weeks after surgery by light and electron microscopy. The apical migration of junctional epithelium was effectively prevented. The fibroblasts synthesized new fibrillar materials and collagen fibrils towards the curetted cementum. The results suggested the possibility that this treatment for periodontally involved teeth would provide ideal root surface conditions for the formation of new fibrous attachment.

Nonoperative Treatment of Acute Knee Ligament Injuries

Nonoperative treatment has received little attention in the numerous scientific reports on knee ligament injuries. Great controversy still exists concerning the proper treatment of a knee with a ruptured ligament, especially the anterior cruciate ligament. However, according to the studies of the authors and an extensive review of the literature the indications for conservative management can be established to be all grade I and II sprains (partial tears) of knee ligaments as well as an isolated grade III sprain (complete tear) of the posterior cruciate ligament. In addition, an isolated complete rupture of an anterior cruciate, or medial or lateral collateral ligament may be treated nonoperatively in an older sedentary person. Other injuries obviously call for an operative approach at the acute stage. Nonoperative therapy protocols must be based on the knowledge of the biological phenomenon occurring during connective tissue healing process. In the first phase of ligament healing the injured knee needs 2 to 3 weeks immobilisation for undisturbed fibroblast invasion and proliferation of collagen fibres. This is achieved by immobilising the knee in a rehabilitative knee brace locked in 40 to 45 degrees of flexion. Thereafter, a gradually increasing controlled mobilisation is allowed in the brace to avoid the deleterious effects of immobilisation to cartilage, bone, muscles, tendons and ligaments, and to enhance the orientation of collagen fibres to the stress lines of the healing ligament. After 4 to 8 weeks the goal for rehabilitation is rapid and full recovery to work and sports. A functional knee brace may be used at this phase to give extra protection before final strengthening of the injured ligament. During the mobilisation and muscle training of the therapy protocol various specific techniques can be used for strengthening of the hamstring and quadriceps muscles, including isometric, isotonic, isokinetic and eccentric exercises with or without resistive equipments. In addition, electrical stimulation may help prevent muscle wasting due to immobilisation, and continuous passive motion may be used to correct persistent extension or flexion deficit. Normally, jogging is allowed approximately 3 to 6 months after the injury, and an athlete is generally able to return to full activity and competitive sports after 6 to 12 months. Quite frequently the whole question of successful rehabilitation after a knee ligamentous injury is more motivational rather than methodological and is thus often independent of attending physician's or physiotherapist's skill or will. Therefore, one of the most important things during rehabilitation is to motivate and encourage the patient for longstanding, intensive work.

Periodontal wound healing responses to varying oxygen concentrations and atmospheric pressures.

Oxygen effects on healing gingival wedge excisions were tested using Sprague-Dawley rats. 40 operated controls were maintained at normal pressure in room air. 3 experimental groups of 40 rats each were exposed for 90 min daily to one of the following: (1) 20.8% oxygen at 2.4 atmospheres pressure, (2) 100% oxygen at 1 atmosphere, or (3) 100% oxygen at 2.4 atmospheres. 5 animals in each group were sacrificed at the following times: 30, 54, 78 h and weeks 1, 2, 3, 6 and 12. Histometric analysis was performed using light microscopy. The connective tissue healing above a reference notch on the maxillary first molar mesial root was assessed. The controls failed to show healing comparable to experimental animals until the end of 2 weeks. Enhanced connective tissue healing above the notch was most significant (p less than or equal to 0.05) in the 2.4 atmospheres pressure groups at 3 and 6 weeks when compared to controls. However, by 12 weeks, no significant differences could be detected. New cementum formation was rare and occasional root resorption was observed. Early connective tissue adaptation does not imply eventual attachment as epithelial downgrowth progressively displaced the connective tissue adjacent to the root in both experimental and control groups of this study.

Normal wound healing compared to healing within porous Dacron implants

This study examined the hypothesis that healing within porous implants differs from that in normal connective tissue. Special attention was given to extracellular components including collagen, reticular fibers, and ground substance, and to enzymes associated with activated macrophages. Using Dacron velour and the rabbit as host, the healing of normal connective tissue and that of the tissue/implant interface were histologically compared 10 and 28 days postimplantation. The results exhibited significant differences between connective tissue healing, implant capsule formation, and granulation tissue generation. The healing of connective tissue and implant capsule formation were essentially complete at 28 days. However, tissue inside the implant was qualitatively different and did not significantly change between 10 and 28 days. It was characterized by macrophages and giant cells, a predominantly acid mucopolysaccharide ground substance, and qualitatively fewer and less well defined collagen and reticular fibers were observed than in normal wound healing. Thus we conclude that the connective tissue inside Dacron velour does not resemble normal connective tissue after 10 or 28 days of healing. Furthermore, the collagen never fully matures into orderly bundles, a phenomenon which may be related to an altered mucopolysaccharide composition and a diminished reticular network. The lysosomal enzymatic activity of the macrophages and perhaps the giant cells at the tissue/implant interface may be linked to these differences.

Influence of the enlargement of the apical foramen in periapical repair of contaminated teeth of dog

Root canals of dogs' premolar teeth were exposed to contamination and to the development of periapical inflammation over a period of 45 days. Root canals were overinstrumented 2 mm beyond the apical foramen with file No. 60 and were underfilled by 2 to 3 mm short of the roentgenographic apex. Ninety days after endodontic treatment, healing and ingrowth of connective tissue into the root canal occurred in 67.8% of the cases. These results suggest that the diameter of the apical foramen and the intensity of the canal contamination are determining factors for periapical tissue repair in cases of pulpal necrosis.

Factors Involved in the Control of Fibroblast Proliferation by Glucocorticoids: A Review

IT IS well established that glucocorticoids exert catabolic effects on connective tissue and delay wound healing. They induce skin atrophy partly by decreasing the proliferative capacity of skin fibroblasts and the synthesis of the ground substance. Despite extensive investigations, the mechanisms of these in vivo steroid effects remain a matter of controversy, since the studies performed to elucidate the actions of adrenal steroids on the proliferation of various types of fibroblasts in vitro have led to contradictory results. Some authors have indeed described an inhibition of the proliferation of fibroblast cultures treated with glucocorticoids, whereas others have reported a stimulatory action of these drugs on cell division. In the present paper, we have attempted to present a comprehensive review of the data and thus provide an explanation for the differences observed among in vitro experiments. In fact, many of the reported discrepancies may be due, in part, to the use of different experimental mod...

Percutaneous healing of clinical tympanic membrane implants.

Percutaneous healing is plagued by materials compatibility problems, epidermal reactions, and mechanical factors. To our knowledge, no studies have evaluated the effects of one of these factors while controlling the others. The tympanic membrane is an implant site where mechanical factors are minimized. Titanium has been shown to be a very histocompatible material, although no reports of the histology of percutaneous titanium implants exist. This study reports on aspects of the epidermal and connective tissue healing around titanium tympanic membrane implants that were explanted from human subjects. The lack of inflammation and the direct adherence of the tissues substantiate the materials compatibility and the absence of mechanical factors. Tissue healing patterns appear to reach an equilibrium which is suitable for the long-term existence of the percutaneous device. This implant location provides a suitable model for studying the tissue reactions to various percutaneous materials.

Recent advances in the treatment of low back pain.

There is at the present time an epidemic of low back pain in the industrialized countries. Although the exact origin of such pain is still unknown, there is increasing awareness that the outcome is usually favourable. Only some 10% of those suffering an acute episode of back pain are incapacitated for more than 6 weeks. The causes of long standing back pain are being identified in an increasing number of patients. They include anatomical and pathological disturbances in the motion segment as well as psychological, social and political causes. There are numerous factors which influence the pathophysiology of the motion segment. The degree of loading has been successfully measured and delineated for various postures and exercises, including those at work. The nutritional pathways to the disc have been established and the effect of various external factors measured. Movement is good for the disc and the importance of continuous passive motion for the healing of diseased or injured connective tissues is not established. Activation of large muscle groups increases the production of the body's pain reducing encephalins. Early diagnosis and early mobilisation of the patient should be of benefit, and long term bed rest and inactivity must be prevented. Fewer cases will need operation in the future. Improved imaging techniques and better methods of operation and fixation will help those few who have a definite pathological lesion amenable to surgery.

Connective tissue regeneration to periodontally diseased roots, planed and conditioned with citric acid and implanted into the oral mucosa.

This investigation used autogenous submucosal implants of root sections to study the connective tissue healing to periodontally diseased roots which had previously been planed and demineralized with citric acid. Eighteen implants were performed, with each being removed 2 to 24 weeks after implantation. The results showed new connective tissue attachment to the old cementum and to the dentin. After 18 weeks, in all specimens new cementum had formed on the dentin, with collagen fibers attached to it. No deposition of new cementum on the old cementum was noted. The formation of new cementum on roots placed in an environment without periodontal ligament cells might be ascribed to the inductive principle of demineralized dentin. The results suggest that a diseased root which has been planed and conditioned with citric acid is likely to form a new connective tissue attachment, even if it is placed in an environment without periodontal ligament cells. They also suggest that the factor inhibiting potential new connective tissue attachment is the condition of the root surface, rather than the lack of an adjacent progenitor cell population.

Epithelial and connective tissue healing following electrosurgical incisions in human gingiva

Electrosurgery is used for intraoral incisions by many clinicians. Much controversy surrounds the effect of lateral heat produced during the electrosurgical incision upon the healing of adjacent connective tissue. Ten electrosurgical incisions were made in the gingiva in each of five adult male volunteers. The duration of incision and actual energy production for each incision were calculated. Excisional biopsies of the incisions were obtained at 0-504 hours. At the light microscopic level, epithelium, totally degenerated immediately following the electrosurgery incision, showed extensive activity at 24-48 hours and had covered all wounds by 72 hours. Early hour specimens showed a homogenous connective tissue region, adjacent to the wound site, devoid of cells and fibers. This zone of denatured connective tissue gradually diminished until it was no longer present at 396 hours.

Healing of periodontal connective tissues following surgical wounding and application of citric acid in dogs.

Topical application of citric acid to a root surface which has been scaled and root planed results in exposure of collagen fibrils of the dentin matrix. The purpose of this study was to examine the healing of gingival connective tissue adjacent to a root planed and subsequently acid conditioned root surface and to determine whether the exposure of dentin or cementum matrix collagen would facilitate the reestablishment of an attachment between the healing connective tissue and the root surface. Full thickness flaps were raised and labial alveolar bone removed over maxillary incisor roots of seven Labrador retrievers. The exposed root surface was planed before etching with citric acid (pH 1) for 3 min. The flap was then repositioned at its original level. Block sections were obtained after 7, 14, 21 and 42 days and the interface between the root surface and the healing wound tissue studied by light and electron microscopy. Compared to conventional flap surgery in the same animals, application of citric acid to the instrumented root surface resulted in an improved rate of connective tissue healing as well as a rapid and consistent reestablishment of connective tissue attachment through extensive interdigitation of new and old collagen fibrils at the tooth‐gingiva interface. Subsequent reinforcement of the established connective tissue attachment included recalcification of the acid‐affected dentin and deposition of new cementum.

The effects of nerve growth factor on bullfrog tadpoles (Rana catesbiana) after limb amputation

AbstractTadpoles of the bullfrog, Rana catesbiana, lose the ability to regenerate limbs at a very early stage of development. Non‐regenerating limbs either show rapid healing of connective tissue over the cut surface with no breakdown of skeletal structures, or else show dedifferentiative processes in the cartilage but the rudimentary blastema formed does not proliferate, and becomes separated from the epidermis by the regrowth of the connective tissue layer. This condition is termed the “critical stage.” When tadpoles were treated with NGF, enlargement of spinal ganglia resulted due to an increase in cell number. The density of nerve fibers in the limbs was likewise increased. This increase in nerve supply to the limbs resulted in a greater incidence of critical stage limbs over non‐regenerating ones, and in several cases, produced limbs which appeared histologically to be, in fact, regenerating.