Wound Healing Pattern Research Articles

Clinical Evaluation of Post-Extraction Site Wound Healing

The aim of this prospective study was to evaluate the clinical pattern of post-extraction wound healing with a view to identify the types, incidence, and pattern of healing complications following non-surgical tooth extraction. A total of 311 patients, who were referred for non-surgical (intra-alveolar) extractions, were included in the study. The relevant pre-operative information recorded for each patient included age and gender of the patient, indications for extraction, and tooth/teeth removed. Extractions were performed under local anesthesia with dental forceps, elevators, or both. Patients were evaluated on the third and seventh postoperative days for alveolus healing assessment. Data recorded were: biodata, day of presentation for alveolus healing assessment, day of onset of any symptoms, body temperature (degrees C) in cases of alveolus infection, and presence or absence of pain. Two hundred eighty-two patients (282) with 318 extraction sites were evaluated for alveolus healing. Healing was uneventful in 283 alveoli (89%), while 35 alveoli (11%) developed healing complications. These complications were: localized osteitis 26 (8.2%); acutely infected alveolus 5 (1.6%); and an acutely inflamed alveolus 4 (1.2%). Females developed more complications than males (p=0.003). Most complications were found in molars (60%) and premolars (37.1%). Localized osteitis caused severe pain in all cases, while infected and inflamed alveolus caused mild or no pain. Thirty patients (12%) among those without healing complications experienced mild pain. Most of the post-extraction alveoli healed uneventfully. Apart from alveolar osteitis (AO), post-extraction alveolus healing was also complicated by acutely infected alveoli and acutely inflamed alveoli. This study also demonstrated a painful alveolus is not necessarily a disturbance of post-extraction site wound healing; a thorough clinical examination must, therefore, be made to exclude any of the complications.

Closure of skin incisions in rabbits by laser soldering: I: Wound healing pattern.

Temperature-controlled tissue laser soldering is an innovative sutureless technique awaiting only solid experimental data to become the gold-standard surgical procedure for incision closure. The goals of the current study were: (1) to define the optimal laser soldering conditions, (2) to explore the immediate skin reparative healing events after sealing the wound, and (3) to determine the long-term trajectory of skin wound healing. Skin incisions were generated over rabbit dorsa and were closed using different wound-closure interventions, in three groups: (a) closure, using a temperature-controlled infrared fiberoptic CO2 laser system, employing 47% bovine serum albumin as a solder; (b) wound closure by cyanoacrylate glues; and (c) wound closure by sutures. The reparative outcomes were evaluated macroscopically and microscopically, employing semi-quantitative grading indices. Laser soldering of incisions at T = 65 degrees C emerged as the optimal method achieving immediate wound sealing. This in turn induced accelerated reparative events characterized by a reduced inflammatory reaction, followed by minimal scarring and leading to a fine quality healing. Temperature-controlled laser soldering offers an accelerated wound reparative process with numerous advantages over the conventional methods. Further investigations may reveal additional benefits in the spectrum of advantages that this innovative surgical technology has to offer. This can introduce new scientific insight that will pave the way for clinical use.

Adipogenic healing in adult mice by implantation of hollow devices in muscle

In mammals, wound healing is thought to result in the formation of scar tissue, with the exception of bony healing after fractures. Here we describe a previously unknown pattern of wound healing in which adipose rather than scar tissue is formed. Adipogenesis is normally confined to the embryo, although there are several experimental models for adipogenesis with highly specific dietary, cytokine, matrix, sex, or age requirements. The adipogenic healing described in this work provides a simple and reproducible experimental mouse model for adipogenesis without these limitations. Mice received intramuscular implants of nylon mesh material. Fibrinous material impregnated implants and within 4 weeks was replaced with highly vascular granulation tissue, typical of wound healing. Also consistent with wound healing was a reduction in vascularity of the newly formed tissue over time (P < 0.05). Lipoblasts were prevalent in granulation tissue, reaching a maximum in week 2 (P < 0.001) but falling to very low levels by week 9. These cells matured to adipocytes, with intermediate forms being seen. The identity of lipoblasts and adipocytes was confirmed by Oil Red O staining and electron microscopy. Control experiments confirmed that adipogenesis was independent of the materials used as well as of the sex and age of the animals. Rather, adipogenesis appeared to be due to replacement of fibrinous material in a space created within muscle. It is possible that adipogenic healing represents an adaptation for limiting the formation of restrictive scar tissues within muscle, and that this is the basis for the formation of traumatic lipomas in humans. Also, muscle tissue is replaced by adipose cells, seemingly derived from pluripotential satellite cells, in several degenerative muscle conditions, suggesting a role for adipogenic healing in these conditions. Anat Rec 267:28–36, 2002. © 2002 Wiley-Liss, Inc.

Adipogenic healing in adult mice by implantation of hollow devices in muscle.

In mammals, wound healing is thought to result in the formation of scar tissue, with the exception of bony healing after fractures. Here we describe a previously unknown pattern of wound healing in which adipose rather than scar tissue is formed. Adipogenesis is normally confined to the embryo, although there are several experimental models for adipogenesis with highly specific dietary, cytokine, matrix, sex, or age requirements. The adipogenic healing described in this work provides a simple and reproducible experimental mouse model for adipogenesis without these limitations. Mice received intramuscular implants of nylon mesh material. Fibrinous material impregnated implants and within 4 weeks was replaced with highly vascular granulation tissue, typical of wound healing. Also consistent with wound healing was a reduction in vascularity of the newly formed tissue over time (P < 0.05). Lipoblasts were prevalent in granulation tissue, reaching a maximum in week 2 (P < 0.001) but falling to very low levels by week 9. These cells matured to adipocytes, with intermediate forms being seen. The identity of lipoblasts and adipocytes was confirmed by Oil Red O staining and electron microscopy. Control experiments confirmed that adipogenesis was independent of the materials used as well as of the sex and age of the animals. Rather, adipogenesis appeared to be due to replacement of fibrinous material in a space created within muscle. It is possible that adipogenic healing represents an adaptation for limiting the formation of restrictive scar tissues within muscle, and that this is the basis for the formation of traumatic lipomas in humans. Also, muscle tissue is replaced by adipose cells, seemingly derived from pluripotential satellite cells, in several degenerative muscle conditions, suggesting a role for adipogenic healing in these conditions.

Progress of ossification and epithelialization of wounds after simple or surgical extractions of teeth in rats with chronic renal failure: an experimental study

Our aim was to investigate the progress of wound healing after simple and surgical removal of the first two molars of the right and left maxillary segments, respectively, in Wistar rats with experimentally induced moderate chronic renal failure (CRF). Sixty Wistar rats were divided into two groups of 30 rats each: experimental and control. CRF was induced in the experimental group by an intraperitoneal injection of cisplatin, 5 mg/kg body weight (BW) initially and then with two maintenance doses of 2.5 mg/kg BW at intervals of one month. The teeth were extracted one month after the last dose of cisplatin. The sockets and the kidneys of all the rats of both groups were evaluated. The mandibles of the 15 rats in the experimental group that developed moderate CRF, together with those of two controls, were evaluated for abnormalities that suggested renal osteodystrophy. The histopathological examination showed: (a) that there were no significant differences in the pattern of wound healing no matter how the tooth was extracted; (b) there were no specific abnormalities in the mandible to indicate of secondary hyperparathyroidism or renal osteodystrophy; and (c) the kidneys of the rats of the experimental group underwent histopathological changes that were significantly different from those in the controls (P< 0.001). Our results indicate that moderate CRF does not have any appreciable or significant modifying effect on wound healing after tooth extraction in Wistar rats.

Quantitative analysis of the development of experimentally induced post surgical adhesions: a microstereological study.

The aim of this study was to quantitatively define the development of post surgical adhesions (PSAs) in a well characterized experimental model and identify possible windows of pathogenesis where pharmaceutical intervention may be most effective. PSAs were induced, in an established rabbit uterine horn model, using standardized reproducible injury, in 17 experimental groups, each with 8 experimental sites and these PSAs were sampled from 30 seconds to 42 days post surgery. Using design based, unbiased stereology, mean volumes of PSAs and associated tissue damage and reaction per experimental site were calculated for each sample time point. PSA development followed the normal pattern of wound healing with surrounding adjacent tissue having a profound influence and interaction. There was a direct relationship between volume of damage (initial and subsequent) and the volume of injury tissue generated. In vivo weak fibrinous PSAs were present from 10 min following injury, with tenacious fibrinous PSAs present from 1 h and onwards. PSA development can be classified into two distinct stages: (i) PSA modelling - occurring during the first 16 h, in which maximum rate of PSA construction is achieved; and (ii) PSA remodelling - from 16 h onwards. Considering this, PSA prevention should ideally be initiated immediately post injury to prevent PSA modelling or, alternatively, during PSA modelling.

Cell viability and inflammatory response in hydrogel sponges implanted in the rabbit cornea

In the quest for the development of a functional keratoprosthesis, the biocompatibility of the porous skirt material in the Chirila keratoprosthesis (KPro) was investigated. The population of live and dead cells within, and the inflammatory response to, a tissue-integrating poly(2-hydroxyethyl methacrylate) (PHEMA) sponge were studied. Samples of the hydrogel sponge were implanted in rabbit corneas and explanted at predetermined time points up to 12 weeks. The explanted sponges were subjected to cell viability assay using two types of fluoroprobes, 5-chloromethylfluorescein diacetate and ethidium homodimer-1. A semiquantitative analysis was performed to assess the number of dead cells within the sponge and in the area of corneal stroma proximal to the sponge. Five rabbits were used for each end point (2, 4 and 12 weeks). To investigate the inflammatory response to the sponge, immunocytochemistry, using specific antibodies to rabbit macrophages, enzyme histochemistry of chloroacetate esterase (to detect neutrophils) and transmission electron microscopy (TEM) were also employed at 24 h, 2, 4 and 12 weeks after implantation. Four weeks after implantation, fewer viable cells were observed in the sponge when compared to the 2-week implant. However, the proportion of viable cells increased dramatically by 12 weeks. The proportion of nonviable cells decreased gradually with time; central sponge contained 34±11% dead cells after 2 weeks, and 15±4.3% after 12 weeks. The staining of inflammatory cells demonstrated the presence of macrophages and neutrophils up to 12 weeks after implantation. TEM confirmed the presence of these cell types and others, including eosinophils and myofibroblasts, as well as blood capillaries. The presence of a significant number of viable cells at each time point and the uniform reduction of the nonviable cell proportion with time suggests that the sponge is a conducive environment supporting a prolific, viable cellular colonization. Dead cells observed in the first instance indicate a normal injury pattern. However, the presence of a small but significant proportion of invading inflammatory cells 12 weeks after implantation confirms a characteristic pattern of wound healing within the sponges.

A laboratory classroom exercise: cell migration in cutaneous wound healing and pigmentary pattern formation in the red-spotted newt.

The black-ringed red spots of the red-spotted newt, Notophfha/mus v. viridescens, consist of a three-cell-type epidermaldermal chromatophore pattern composed of epidermal erythrophores underlaid with dermal iridophores which are surrounded by a ring of dermal melanophores. Throughout the skin of the dorsum there are scattered epidermal melanophores and scattered dermal iridophores and melanophores (Forbes et a/., 1973). In this open-ended laboratory exercise, students create fullthickness skin wounds on the dorsum of adult newts and follow early (24 h), and perhaps later(weeks to months), healing of the wounds. An interesting aspect of this system for short term observation is that the leading edge of the wound-healing epithelium, as well as epidermal melanophores, can be visualized with a dissecting microscope. The melanophores in the migrating epithelium serve as naturally marked cells. Students can observe clearly the complete re-epithelialization of a one-by-two mm rectangularwound in less than twenty-four hours. Furthermore, jf the wound is made near one of the black-bordered red spots or between two closely spaced spots, the (epidermal) erythrophores of the spot(s) are carried into the wound epithelium allowing one to follow individual large bright red cells as wound epithelialization occurs (Zaccaria, unpub. obs.) (Figs. 1 and 2). In long term observation, such migrated erythrophores attract (dermal) iridophores which can be seen individually to migrate into the wound area (Fig. 2), and to come to reside in the dermis directly beneath the erythrophores. This takes a few weeks and is a striking in vivo demonstration of directed cell migration. Under even longer term observation, about two months, dermal melanophores migrate into the area of the wound and cluster around this epidermal-dermal erythrophore-iridophore association, thus creating a three-cell-type chromatophore pattern which

Transient Morphological and Biochemical Alterations of Arterial Proteoglycan during Early Wound Healing

Proteoglycan alterations in the carotid arteries of normolipemic rabbits during the first 14 days after injury were evaluated by morphometric analysis of ruthenium red-stained sections using transmission electron microscopy and by incorporation of 35S-sulfate. Two types of de-endothelializing injury were compared, air-drying and balloon catheter. Three days after either injury, a transient increase in concentration of 35S-labeled glycosaminoglycans, changes in distribution of 35S-sulfate among glycosaminoglycans, and a two- to threefold increase in 35S-sulfate content (measured as 35S/μg glycosaminoglycan) were observed. Morphometric analysis revealed an alteration in medial proteoglycan distribution and morphology at 3 days after injury, which was more evident after air-drying than balloon injury. In response to either injury, metabolically activated smooth muscle cells were associated with very large proteoglycan granules (diameter: >60 nm) which possibly contained glycosaminoglycans with longer chains and/or altered charge densities. By 14 days after either injury, the distribution of medial proteoglycan returned to normal and a neointima formed. The neointima was thicker following balloon injury, but irrespective of the nature of the injury proteoglycan concentration was higher in the re-endothelialized than in non-reendothelialized areas. The alterations in extracellular proteoglycan of the intima-medial layers induced by these two forms of injury may influence the pattern of wound healing but are not associated with lipid deposition within the time frame examined.

The Surgical Treatment of Tendinitis: Clinical Rationale and Biologic Basis

The rationale for surgical treatment of tendinitis is to induce a modulation of the tendon cell-matrix environment by either promoting a renewed wound repair cycle or by the removal of aberrant tissue. The adequacy of healing as a result of surgical tendon treatment has been poorly documented histologically; what evidence exists suggests normal tissue is not achieved. The clinical experience of the authors as well as preliminary analysis of wound healing patterns in a longitudinal internal tenotomy rabbit tendo-Achilles model are discussed.

Ontogenetic transition of wound healing pattern in rat skin occurring at the fetal stage

Full-thickness excisional wounds were made in the dorsal skin of rat fetuses at day 16 and day 18 of gestation. A small patch of skin surrounding the open wound was cut out, mounted on a plastic ring and incubated in an organ culture system. In the presence of serum, the open wound in the day-16 fetal skin closed within three days of culture. During the wound-closure process, no new structures were formed in the wound space, and no conspicuous changes were noted in the histological architecture of the surrounding skin during culture, indicating that the wound closure may result from a centripetal movement of the surrounding skin only. In contrast, the size of the open wound in the day-18 fetal skin remained almost unchanged for one week, but a thin acellular network spread over the wound space within one day of culture. The predominant component of the network was cross-linked fibrin, as disclosed by scanning electron microscopy and sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by immunoblotting. The network served as a scaffold for the ingrowth of fibroblast-like cells. These stage-dependent differences in fetal wound healing were consistent with an in vivo study showing that the day-16 wound was covered with the surrounding skin itself, whereas the day-18 wound was covered with newly formed epidermis and invaded by inflammatory cells. The present investigation strongly indicates the prenatal occurrence of a fetal-to-adult transition in the wound-healing pattern of rat skin.

One-year inhalation toxicity study of formaldehyde in male rats with a damaged or undamaged nasal mucosa.

To study the effect of bilateral intranasal electrocoagulation damage on the susceptibility of rats to formaldehyde vapour, male Wistar rats with a damaged or undamaged nasal mucosa were exposed to atmospheres containing 0, 0.1, 1 or 10 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 or 52 weeks. Electrocoagulation damage was induced in the anterior third part of the nose. The repair process followed the pattern of wound healing. Loss of turbinates and perforation of the septum were common irreversible findings. After 13 weeks basal cell hyperplasia and squamous metaplasia of the respiratory epithelium, and rhinitis were still visible. After 52 weeks effects attributable to electrocoagulation were slight basal cell hyperplasia and some rhinitis. Major formaldehyde-related adverse effects in the 10 ppm group not subjected to electrocoagulation included growth retardation, reduced urine production, and rhinitis accompanied by squamous metaplasia of the nasal respiratory epithelium. No adverse effects were seen at 0.1 or 1 ppm in rats with an intact nasal mucosa. The principal untoward effects of formaldehyde in electrocoagulation-treated rats seen after 13 and/or 52 weeks comprised increase in basal cell hyperplasia, squamous metaplasia of the nasal respiratory epithelium, damage to the olfactory epithelium at 10 ppm, and focal squamous metaplasia of nasal respiratory epithelium at 0.1 and 1 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Heparin on the Wound Healing Response to Collagen Implants in vivo

The biologic response to fibrillar collagen (collagen) and fibrillar collagen plus heparin(collagen/heparin) implants have been compared in the rat subcutaneous and guinea pig dermal wound models. The reconstituted bovine dermal collagen implants were injected subcutaneously in rats at concentrations ranging from 18 to 30 mg/ml and in volumes ranging from 0.5 to 1.0 ml. The biologic response to the collagen implants alone was characterized by a transient invasion of a modest number of inflammatory cells within the first three days of implantation that was followed by limited fibroblast invasion into the peripheral 1/3 of the implant during the course of the next three to four weeks. Occasionally, blood vessels were observed to invade the peripheral regions of the implant. The degree (number) and extent (depth) of cell invasion were inversely related to initial collagen implant concentration. Addition of heparin (0.3-20 μg/mg collagen) to these implants resulted in a significant dose-dependent increase in the degree and extent of fibroblast invasion. Radiolabeling studies showed that the collagen and collagen/heparin implants were cleared from the subcutis at identical rates. Implantation of these formulations in a guinea pig dermal wound model was also performed, using a semi-occlusive wound dressing (Opsite) to maintain the implant in the wound site. The fibrillar collagen implant alone was pushed upward by developing granulation tissue at the base of the wound and served as a support for epidermal cell migration, proliferation, and differentiation as wound closure proceeded. The implant was slowly invaded and turned over as granulation tissue developed from the base and margins of the wound bed. The inclusion of heparin in these implants resulted in a significantly different pattern of wound healing. The collagen/heparin implants histologically presented a more broken-up or porous appearance following implantation, which was associated with a greater degree of penetration of developing granulation tissue into the implant itself as compared to the collagen implants. Radiolabeling studies revealed that clearance rates of implants with and without heparin from wound sites were similar, as noted in the rat subcutis. Laser doppler flowmetry studies suggested that the heparin-containing implants were more vascular than control wound sites or sites treated with collagen alone.

顎骨欠損に対する自家肋骨移植創の神経線維の消長について

Partial bone defect of the mandible was made in adult dogs and a fresh autogenous rib-bone was grafted in each. A neuropathohistological study was made of the nerve distribution in the healing process of fresh autogenous rib-bone graft wounds. Results are summarized as follows : 1. General healing process as studied in the present fresh autogenous rib-bone grafted wounds seemed to follow the usual pattern of wound healing. 2. From 3rd day after grafting, the nerve fibers in the grafted rib-bone began to degenerate and completely disappeared on 7th day. 3. From 3rd day to 5th day, the central inferior alveoral nerve suffered a slight degeneration, or so-called primary degeneration. 4. On 3rd day at the peripheral side, the inferior alveolar nerve and the nerve fibers of the bone marrow reached the height of degeneration. On 7th day, the nerve fibers of the bone marrow disappeared and the inferior alveolar nerve on 15th day. 5. Regeneration of the nerve fibers at the grafted site started on 5th day in the central bone marrow, and on 7th day in the central inferior alveolar nerve. The regenerated nerve fibers reached the part of the peripheral conjunction on 45th day after grafting. 6. On 70th day after grafting, infiltration and proliferation of the Schwann cells from the central and peripheral inferior canals were found at the trabecula in the grafted bone. On 30th day, the regenerated nerve fibers penetrated into these arears. These regenerated nerve fibers extended mainly from the central inferior alveolar nerve but there were some penetrating from the wall of the wound and the periosteum. 7. On 180th day after grafting, the distribution of the nerve fibers in the grafted bone was normal. 8. Formation of the bony space appearing to be the inferior canal occured in the grafted bone on 120th day. The usual large nerve bundle was not observed in the bony space even on 180th day after grafting. 9. In the peripheral inferior canal, regenerated nerve fibers were found penetrating from the central side through the grafted bone and the graft-wounds. 10. On 180th day, the distribution of the nerve fibers in the peripheral bone marrow and the periodontium was nearly the same as that of the normal ones. As is stated above, it is clear that autogenous rib-bone graft for bone defect greatly affects nerve distribution, especially regeneration of the inferior alveolar nerve in the healing process of the graft wound.

局所自家骨小片移植創の治癒過程における神経線維の消長に関する実験的研究

The author performed enucleation of the tooth germ in the 4th premolar of mandible of young adult dogs grafted local autogenous bone chips. A neuro-pathohistological study was made of the change of the nerve distribution in the healing process of local autogenous bone chips grafted wounds. Results are summarized as follows, 1. General healing process as studied in the present local autogenous bone chips grafted wounds seemed to follow the usual pattern of wound healing. 2. The whole process of nerve distribution in the healing of local autogenous bone chips grafted wounds could be distinguished into following 4 stages. 1. Degeneration stage : to 5th day after grafting. 2. Regeneration stage : 5th day to 20th day. 3. Readjustment stage : 20th day to 30th day. 4. Completion : after 30th day. 3. To 5th day after grafting, the cut surface of the bundle of nerve fibers in the wound and the neighbouring bundle of the inferior alveolar nerve suffered the so-called Waller's degeneration sleightly. 4. Regeneration of the nerve fiber started by the 5th day, and became most vigorous from 10th day to 15th day. 5. On about 20th day, there were seen in the wounds three distinct groups of nerve fiber bundles, two which ascended along both lateral walls and the third through the middle of the wound, and small bundles of nerve fibers branching of from these groups formed large networks in the wound socket. 6. As the Haversian Canaliculi and the bone marrow completed forming in the new bone on about 30th day, the nerve bundles were adjusted and single nerve fibers decreased. As is stated above, it was made clear that the nerve distribution in the healing process of the grafted wounds was slightly affected by local autogenous bone chips.

Combined surgical and radiation injury. VII. Trace element studies of the healing wound.

SummaryIonizing radiation in the midlethal range retards the wound healing pattern in rats. Iron, copper, and zinc content was sequentially determined in the granulation tissue of wounds of irradiated and nonirradiated rats for a period of 12 days following wounding. The copper levels remained constant in both groups. The granulation tissue iron content paralleled the wound healing pattern. In irradiated animals where wound healing is delayed by 4 days, the iron curve is also delayed. The granulation tissue zinc content of nonirradiated rats increased from days 4 to 12 during the period of most rapid wound contraction. The wound zinc content of the irradiated rat was decreased during this period.

Combined surgical and radiation injury. IV. Effect of antimicrobials on the wound healing pattern of the x-irradiated rat.

The effect of treatment with tetracycline, streptomycin, or chloramphenicol on mortality and wound healing patterns of irradiated and nonirradiated rats was assessed. The administration of tetracycline and streptomycin diminished the mortality in combined radiation and surgical injury; chloramphenicol, streptomycin, or tetracycline did not change the normal wound healing pattern in nonirradiated animals, nor did the administration of these antimicrobials restore the wound healing pattern in the irradiated animal to normal. These data suggest that infection may not play a primary role in the delay in wound contraction attendant to radiation injury.

Combined surgical and radiation injury. 3. The effect of pre-irradiation radioprotective drug treatment.

The radioprotective compounds studied do not alter the wound healing pattern in the nonirradiated rat when wounding follows drug administration by 4 days. These compounds also do not demonstrate any deleterious interaction with wounding under these circumstances. The radioprotective compounds studied promoted the wound healing pattern of irradiated, wounded rats toward the pattern of nonirradiated wounded rats. The increased mortality observed with the combination of a nonlethal surgical wound and radiation was not observed in animals treated prior to radiation with the radioprotective agents studied (MEA, serotonin, and WR 2721-C).