First Week Of Healing Research Articles

A Comparative Study of Mucosal Wound Healing after Excision with a Scalpel, Diode Laser, or CO2 Laser.

Forty-five Sprague Dawley rats were used in this study. These rats were divided into two laser intervention groups (CO2, n = 15; diode, n = 15) and one control group with scalpel excision (n = 15). The effectiveness of therapy has been assessed based on the comparison of intraoperative, postoperative, and histological parameters on days 7, 21, and 35, and postoperative weight changes as pain indicator. Both laser groups demonstrated significantly (P < 0.05) less bleeding than did the control group during the intraoperative stage, whereas the CO2 laser showed more precise cutting compared with the diode laser (P < 0.05). The highest healing score was reported in the CO2 and scalpel groups on the first week of healing than in the diode group (P < 0.05). However, no significant difference was observed between the groups on days 21 and 35. Weight loss was significantly (P < 0.05) demonstrated in the diode group compared to the scalpel and CO2 groups till day 7. Both laser groups demonstrated delayed healing process compared with the scalpel. Nevertheless, the CO2 group followed the scalpel trends after day 7. Scalpel and CO2 laser yielded a superior clinical outcome compared with the diode excision of oral mucosa, whereby the CO2 has been proposed as the most effective laser type at the end of the first postoperative month.

Landscape of Well-Coordinated Fracture Healing in a Mouse Model Using Molecular and Cellular Analysis.

The success of fracture healing relies on overlapping but coordinated cellular and molecular events. Characterizing an outline of differential gene regulation throughout successful healing is essential for identifying crucial phase-specific markers and may serve as the basis for engineering these in challenging healing situations. This study analyzed the healing progression of a standard closed femoral fracture model in C57BL/6N (age = 8 weeks) wild-type male mice. The fracture callus was assessed across various days post fracture (D = days 0, 3, 7, 10, 14, 21, and 28) by microarray, with D0 serving as a control. Histological analyses were carried out on samples from D7 until D28 to support the molecular findings. Microarray analysis revealed a differential regulation of immune response, angiogenesis, ossification, extracellular matrix regulation, mitochondrial and ribosomal genes during healing. In-depth analysis showed differential regulation of mitochondrial and ribosomal genes during the initial phase of healing. Furthermore, the differential gene expression showed an essential role of Serpin Family F Member 1 over the well-known Vascular Endothelial Growth Factor in angiogenesis, especially during the inflammatory phase. The significant upregulation of matrix metalloproteinase 13 and bone sialoprotein from D3 until D21 asserts their importance in bone mineralization. The study also shows type I collagen around osteocytes located in the ossified region at the periosteal surface during the first week of healing. Histological analysis of matrix extracellular phosphoglycoprotein and extracellular signal-regulated kinase stressed their roles in bone homeostasis and the physiological bone-healing process. This study reveals previously unknown and novel candidates, that could serve as a target for specific time points in healing and to remedy cases of impaired healing.

Assessment of sheep knee joint after ACL replacement with Achilles tendon autograft and PLA-based implant

In this study, we propose a new approach in the anterior cruciate ligament (ACL) replacement to provide stability and integration with bone tunnel. A polylactide (PLA)-based tubular implant was used to support the graft stabilization in femoral and tibial bones and to stimulate the healing process after (ACL) replacement on a sheep model. The ACL was replaced with an autologous Achilles tendon split graft. The tendon-to-bone healing in the model was analyzed after 6 and 12 weeks. Two groups of animals were compared, i.e. the group with the PLA-based implant used in the ACL replacement and the control group without the implant. The knee joints were mechanically and clinically evaluated, including the histopathology tests, to determine their stability and integrity. The results indicated that the bioresorbable PLA-based tubular implant may facilitate integration of the tendon graft with bone. Remodeling the allograft inside the implant improves the joint mobility from the first week of healing: no pathological changes were observed at the surgery site and in the animals’ mobility. After 6 and 12 weeks of healing no significant changes in the mechanical parameters of the knee joint were observed, regarding the joint failure force, knee displacement, angular mobility range and joint stiffness. Relatively small values of the non-destructive tests in the knee displacement, already 6 weeks after surgery, indicated the early stabilization of the knee joint. The studies showed that the failure forces of knee joints after the ACL replacement with the PLA-based implant are lower than those of an intact joint, although their biomechanical features, including strain-at- failure, are similar.The biomechanical parameters of the knee joint were significantly improved due to the selected method of attaching the autograft ends to the femoral and tibial bone surfaces. After 12 weeks the intra-tunnel tendon-bone site with the PLA implant revealed the better tibia-femur joint mechanical stability, linear force-strain function and the decreasing strain-to-failure value, as compared to the control group.

Healing of donor sites of connective tissue grafts harvested by the single incision technique: A randomized clinical trial evaluating the use of collagen hemostatic sponge with or without sutures.

The aim of this study was to evaluate the effect of suturing on the early wound healing of donor sites of subepithelial connective tissue grafts (SCTG), harvested by the single incision technique (SIT), following the application of a collagen sponge. Thirty-six patients were randomized to receive a collagen sponge with or without sutures in the palatal donor sites following connective tissue grafting via the SIT. Outcome variables were early healing index (EHI) at 7, 14, and 30 days, self-reported pain using a visual analogue scale (VAS) recorded on the 0 to 100 scale at 7 and 14 days, and immediate and delayed bleeding. No significant differences were found between groups at baseline. EHI index showed no differences between groups in all-time intervals. Eight subjects from suture group (SG) and 10 from no suture group (nSG) showed complete wound closure at day 14 (P>0.05) and at 30 days, complete closure was observed in 35 out of 36 patients. Four subjects from the SG and three from the nSG had immediate bleeding (P>0.05), while delayed bleeding was observed in two subjects from the SG and three from the nSG during the first week of healing (P>0.05). No differences were found in VAS scale between groups (SG, 36.2 ± 24.8; nSG, 21.5 ± 24.2, P>0.05). It can be concluded that when a collagen sponge is placed in palatal donor areas of SCTG harvest by means of the SIT (incision length of ≈15mm), sutured and non-sutured sites display similar early wound healing outcomes and patient-reported outcomes.

Evaluation of the Effect of Hyaluronic Acid Application on the Vascularization of Free Gingival Graft for Both Donor and Recipient Sites with Laser Doppler Flowmetry: A Randomized, Examiner-Blinded, Controlled Clinical Trial.

This study aimed to evaluate with laser Doppler flowmetry (LDF) the effect of topical hyaluronic acid (HA) application on the vascularization of free gingival graft (FGG) donor and recipient sites during the early wound healing period and to investigate the effect of HA application on the dimensional change of the FGG. Forty systemically healthy, nonsmoking patients who required FGG due to insufficient amount of attached gingiva in a partial edentulism were randomly assigned to a study group: test (FGG+HA) or control (FGG alone). The LDF values of the donor and recipient sites were measured in both groups before the operation and at 4, 7, 10, 14, and 30 postoperative days. LDF measurement of the graft was performed as soon as the graft was taken from the palatal site. FGG dimensions (width, height, and thickness) were assessed and recorded at baseline and on day 30, as well as the percentage of the changes in these values. LDF values of the recipient site in the FGG+HA group were found to be statistically higher than those in the control group on days 4 and 7 (P = .013 and P = .020, respectively); however, no differences were found for days 10, 14, and 30. Additionally, no differences were found for the LDF values of the palatal site between the FGG+HA and control groups (P > .05) at all examined time points. The height of the graft measured on day 30 was statistically higher in the FGG+HA than the control group (P < .001). The percentage change in thickness and height of the FGG was statistically lower in the FGG+HA than control group (P = .028 and P < .001, respectively). Application of HA on the recipient bed under the FGG at the first week of healing allows the formation of a well-vascularized layer, which acts as a barrier against tissue tensions by functioning as a scaffold between the recipient bed and FGG, thus reducing the shrinkage of the graft, especially in the vertical direction. This study further showed that the graft taken from the donor site had a remaining blood perfusion value of its own.

The effect of magnesium on early osseointegration in osteoporotic bone: a histological and gene expression investigation

SummaryMagnesium has a key role in osteoporosis and could enhance implant osseointegration in osteoporotic patients. Titanium implants impregnated with Mg ions were installed in the tibia of ovariectomized rats. The release of Mg induced a significant increase of bone formation and the expression of anabolic markers in the peri-implant bone.IntroductionThe success of endosseous implants is highly predictable in patients possessing normal bone status, but it may be impaired in patients with osteoporosis. Thus, the application of strategies that adjuvate implant healing in compromized sites is of great interest. Magnesium has a key role in osteoporosis prevention and it is an interesting candidate for this purpose. In this study, the cellular and molecular effects of magnesium release from implants were investigated at the early healing stages of implant integration.MethodsOsteoporosis was induced in 24 female rats by means of ovariectomy and low-calcium diet. Titanium mini-screws were coated with mesoporous titania films and were loaded with magnesium (test group) or left as native (control group). The implants were inserted in the tibia and femur of the rats. One, 2 and 7 days after implantation, the implants were retrieved and histologically examined. In addition, expression of genes was evaluated in the peri-implant bone tissue at day 7 by means of quantitative polymerase chain reactions with pathway-oriented arrays.ResultsThe histological evaluation revealed that new bone formation started already during the first week of healing for both groups. However, around the test implants, new bone was significantly more abundant and spread along a larger surface of the implants. In addition, the release of magnesium induced a significantly higher expression of BMP6.ConclusionsThese results provide evidence that the release of magnesium promoted rapid bone formation and the activation of osteogenic signals in the vicinity of implants placed in osteoporotic bone.

The influence of collagen membrane and autogenous bone chips on bone augmentation in the anterior maxilla: a preclinical study.

To evaluate the effect of a resorbable collagen membrane and autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) on the healing of buccal dehiscence-type defects. The second incisors and the first premolars were extracted in the maxilla of eight mongrels. Reduced diameter, bone-level implants were placed 5weeks later. Standardized buccal dehiscence-type defects were created and grafted at implant surgery. According to an allocation algorithm, the graft composition of each of the four maxillary sites was DBBM+membrane (group D+M), autogenous bone chips+DBBM+membrane (group A+D+M), DBBM alone (group D) or autogenous bone chips+DBBM (group A+D). Four animals were sacrificed after 3weeks of healing and four animals after 12weeks. Histological and histomorphometric analyses were performed on oro-facial sections. The pattern of bone formation and resorption within the grafted area showed high variability among the same group and healing time. The histomorphometric analysis of the 3-week specimens showed a positive effect of autogenous bone chips on both implant osseointegration and bone formation into the grafted region (P<0.05). The presence of the collagen membrane correlated with greater bone formation around the DBBM particles and greater bone formation in the grafted region after 12weeks of healing (P<0.05). The oro-facial width of the augmented region at the level of the implant shoulder was significantly reduced in cases where damage of the protection splints occurred in the first week of healing (P<0.05). The addition of autogenous bone chips and the presence of the collagen membrane increased bone formation around DBBM particles. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area.

Assessment of the healing activity of polyelectrolyte complexes through molecular and histological characterization

Wound dressings based on composites of polymers are widely used for activating the healing process, but the expression of genes related to the growth of new tissue during healing, activated by these dressings has not been widely investigated. This study examined the effects of polyelectrolyte complex (PEC) made of the alginate and chitosan biomaterials in the form of hydrogel on the healing of excision wound. This was through studying of the changes in the expression of two angiogenic genes (vascular endothelial growth factor (VEGF) and Von Willebrand factor (vWF)) during the healing progress with real time polymerase chain reaction supported by assessing the accompanied histological changes within the healing wounds. Complete healing was observed after 16 days of the hydrogel application, but no complete closure was observed for the non-treated wounds even after three weeks of healing. The VEGF expression was enhanced in the treated wounds to reach its maximum by the 7th day referring that the two polyelectrolytes within the complex could maintain the angiogenic cascade for accelerated wound closure as well as its possible usage as a marker for enhanced neo skin tissue growth. In contrast, there were low expression levels of the vWF gene in blood cells during the first week of healing of the treated wounds, which began then to increase along with the decreasing of VEGF expression which may be due to the hemostatic effects of the used complex in the wound area. This may prove the efficiency of the hydrogel with its PEC structure in the treatment of acute wounds with accelerating the supply of blood vessels for neo tissue growth.

Diabetic Wounds Exhibit Decreased Ym1 and Arginase Expression with Increased Expression of IL-17 and IL-20.

Objective: Impaired wound healing in diabetic (DB) patients is a significant health problem; however, the roles that cytokines and innate immune cells contribute to this impaired healing are not completely understood. Approach: A mouse model was used to compare the innate immune response during DB and normal wound healing. Two 5-mm full-thickness wounds were created on the dorsal skin of BKS.Cg-m+/+Leprdb/J (DB) and C57BL/6 (wild-type) mice. Innate immune cell markers and cytokine mRNA levels were measured in wound biopsies during the first week of healing. Results: Innate immune cell influx (typified by the Gr-1 neutrophil marker and the Ym1 macrophage marker) was delayed in the DB wounds. Expression of the M2 macrophage-related genes, Ym1 and arginase 1, was significantly reduced in the DB wounds. PCR array analysis demonstrated altered cytokine expression in DB wounds. Most prominently, both interleukin (IL)-17 and IL-20 mRNA levels were significantly increased in the DB wounds. Innovation: This is the first study to identify increased levels of IL-17 and IL-20 in DB wounds. These cytokines are also elevated in the inflammatory skin disorder, psoriasis; thus, they may be potential therapeutic targets to aid in DB wound healing. Conclusion: The entire cytokine profile of DB wounds over the course of healing is not completely understood. This study suggests that the IL-17 and IL-20 families of cytokines should be further analyzed in the context of DB wound healing.

In vivowound healing diagnosis with second harmonic and fluorescence lifetime imaging

Skin wounds heal when a series of cell lineages are triggered, followed by collagen deposition, to reconstruct damaged tissues. This study evaluates the regeneration of collagen and change in cellular metabolic rate in vivo during wound healing in rats, with second harmonic generation (SHG) and fluorescence lifetime imaging microscopy respectively. The metabolic rate of cells is reflected through the lifetime of the autofluorescence from the co-enzyme protein, reduced nicotinamide adenine dinucleotide, due to its change in the relative concentration of bound and free forms. A higher than normal cellular metabolic rate is observed during the first week of healing, which decreases gradually after eight days of wound formation. SHG signal intensity change indicates the net degradation of collagen during the inflammatory phase, and net regeneration begins on day five. Eventually, the quantity of collagen increases gradually to form a scar tissue as the final product. Importantly, this work demonstrates the feasibility of an in vivo imaging approach for a normal wound on rat skin, which has the potential to supplement the noninvasive clinical diagnosis of wounds.

TiNOx coatings on roughened titanium and CoCr alloy accelerate early osseointegration of dental implants in minipigs

IntroductionTitanium nitride oxide (TiNOx) coatings are known for their biocompatibility, hardness and high resistance to corrosion and wear. Further, they can be applied by plasma vapor deposition onto a wide variety of metallic, mineral, or organic substrates.In cell cultures, TiNOx coatings applied onto SLA (sandblasted, large grit, acid etched)-roughened titanium surfaces increased human primary osteoblast proliferation by 1.5 times in the first 2weeks after seeding, while maintaining a high degree of cell differentiation.Therefore, the objectives of the present study were (i) to determine whether these findings would translate into the enhanced osseointegration of TiNOx-coated implants in vivo and (ii) to compare the osseointegration of Ti-SLA (titanium–SLA) and CoCr-SLA (cobalt–chromium–SLA) implants coated with TiNOx. MethodsForty‐eight cylinders made of Ti-SLA, Ti-SLA-TiNOx (TiNOx‐coated Ti-SLA) and CoCr-SLA-TiNOx (TiNOx‐coated CoCr-SLA) were implanted into the lower jawbone of 8 minipigs. The bone-to-implant contact was determined after 1week, 2weeks, 1month and 3months. ResultsOsseointegration proceeded normally on all 3 surfaces, with equal activity after the first week of healing. After 2weeks, bone-to-implant contact was 1.8 times higher on TiNOx coatings, either deposited on Ti or on CoCr. These differences fell off after 1 and 3months of healing. ConclusionsWhen compared to standard SLA titanium, TiNOx coatings enhance implant osseointegration during the first month of healing. Furthermore, this stimulating effect is independent of the substrate, leading to similar results whether the coating is applied onto SLA-Ti or onto SLA-CoCr.

Healing of complement activating Ti implants compared with non-activating Ti in rat tibia

Recent studies have revealed that ozone ultraviolet (UVO) illumination of titanium (Ti) implants improves bone–implant anchorage by altering the physico-chemical and immune activating properties of the titanium dioxide (TiO2) layer. In the present rat tibia model, the authors compared the early events of inflammation and bone formation around UVO-treated Ti and complement activating immunoglobin g (IgG)-coated Ti. Machined Ti and machined Ti coated with a physical vapour-deposited Ti layer were used as references. Screw-shaped test and reference implants were implanted into rat tibia and harvested after 1, 7 and 28days. Messenger RNA expression of implant adhered cells and peri-implant tissue ∼250μm from the surface were subsequently analysed with regard to IL-1β, TNF-α, osteocalcin, cathepsin K, BMP-2 and PDGF. Separate implants were retrieved after 7 and 28days for removal torque measurements, and histological staining and histomorphometric analysis of bone area and bone-to-implant contact. While enhanced expression of inflammatory markers, TNF-α and IL-1β, was observed on IgG-coated surfaces throughout the observation time, UVO-treated surfaces indicated a significantly lower early inflammatory response. In the early phases (1 and 7days), the UVO-treated surfaces displayed a significantly higher expression of osteoblast markers BMP-2 and osteocalcin. In summary, complement activating Ti implants elicited a stronger inflammatory response than UVO-treated Ti, with low complement activation during the first week of healing. In spite of this, the UVO-treated Ti induced only marginally more bone growth outside the implants.

The effect of zoledronate during bone healing

BackgroundBisphosphonates have become the treatment of choice for a variety of bone diseases in which excessive osteoclastic activity is an important pathologic feature. However, inhibition of osteoclastic activity could lead to inhibition of remodeling during bone healing or repair. The objective of this study is to investigate the effect of zoledronate (the most potent bisphosphonate) in the biological process of bone healing.MethodsThirty immature male rabbits were divided into two groups (control and experimental) of 15 animals each. Both groups were submitted to fibular osteotomy. Only in the experimental group a single dose of zoledronate was administered. After 1, 2, and 4 weeks, animals of both groups were euthanized and the osteotomy site was histomorphometrically evaluated. The associated parameters analyzed were tissue volume (TV), fractional trabecular bone volume (BV/TV), fractional woven bone volume (WoV/TV), fractional periosteal fibrous volume (FbV/TV), and medullary fibrous volume (MaV/TV).ResultsThe first week of healing was characterized by small callus area (experimental group) and less periosteal fibrosis. The second week was characterized by a large quantity of woven bone and marked decrease in periosteal fibrosis in the two groups. In the control group there was also a significant increase in trabecular bone. The fourth week was characterized by increased amount of woven bone and trabecular bone in the experimental group; there was increased medullary fibrosis in the two groups, while there continued to be significantly less periosteal fibrosis in the experimental group.ConclusionsZoledronate does not prevent bone healing. However, the effect of zoledronate was characterized by accentuated stimulation of primary bone production and probably inhibition of remodeling, leading to retention of trabecular bone.

How to treat and identify device infections

The incidence of device-related infections depends directly on the definition employed. The lack of precision is also compounded by the latency between the initiation and manifestation of the infection. It is not rare for there to be some erythema at the incision site during the first week of healing, and it is not clear that this represents infection. Less frequent, but still common, there can be a small, superficial stitch abscess, which will respond to local measures. When the diagnosis of device system infection is made, it should be made on the basis of pocket cellulitis, erosion, abscess, persistent bacteremia, or endocarditis with or without vegetation on the lead.

Interpenetrating polymer networks containing gelatin modified with PEGylated RGD and soluble KGF: Synthesis, characterization, and application in in vivo critical dermal wound

The purpose of this study was to evaluate the biocompatibility and the efficacy in wound healing of a gelatin-based interpenetrating polymer network (IPN) containing poly(ethylene glycol) (PEG)-ylated RGD and soluble KGF-1 (RGD-IPN+KGF). IPNs were applied to full-thickness wounds on a rat model. Wound healing was assessed through histological grading of the host response and percent area contraction at 2 days, 1 week, 2 weeks, and 3 weeks. A control IPN containing unmodified gelatin (unmod-IPN) and a conventional clinical bandage were applied to similar wounds and also evaluated. During the first week of healing, the unmod-IPN and conventional dressing wound showed a greater amount of contraction than that of RGD-IPN+KGF. However, by 3 weeks the extent of wound contraction was comparable between treatments. The RGD-IPN+KGF treated wound demonstrated lower macrophage and fibroblast densities at 3 weeks as compared to unmod-IPN treated wounds. RGD-IPN+KGF acted as a tissue scaffold while preventing the entry of foreign bodies, advantages not seen with the conventional dressing. The extent of cellularity and extracellular matrix organization was higher for wounds healed with RGD-IPN+KGF than those healed with unmod-IPN. These results indicate that both soluble and immobilized bioactive factors can be incorporated into our IPN platform to enhance the rate and the quality of dermal wound healing.

Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.

The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well as in epithelial cancers, and has an established role in angiogenesis and tissue repair. Because of these physiological effects and the widespread use of the selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition of COX-2 would affect incisional skin wound healing. Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, we evaluated the role of COX-2 in the wound healing process by comparing the effects of a nonselective COX inhibitor, diclofenac, with a selective COX-2 inhibitor, SC-791. Healing was monitored for up to 28 days postincision histologically and for recovery of wound strength. COX-2 expression was observed over the first week of healing, peaking at day 3 and was not affected by treatment with the selective COX-2 or nonselective COX inhibitors. Infiltrating macrophages, as well as keratinocytes and dermal fibroblasts at the wound site, expressed COX-2. Neither selective COX-2, nor nonselective COX inhibition had a significant effect on the macroscopic or microscopic morphology of the wounds, whereas dexamethasone treatment resulted in epidermal and granulation tissue atrophy. In addition, neither selective COX-2, nor nonselective COX inhibition altered keratinocyte proliferation and differentiation, dermal angiogenesis or the recovery of wound tensile strength, whereas dexamethasone reduced the tensile strength of the wounds by 30-38% throughout the healing period. These data indicate that selective COX-2 inhibition does not affect the healing of surgical skin wounds.

A metaphyseal defect model of the femur for studies of murine bone healing

A bone defect model was developed in the distal metaphysis of the femur for studies on bone healing in the mouse. The circular defect involving 20% of the bone circumference resulted in a 34% reduction in the bending moment compared to intact bone. The healing process was followed using histomorphometry, peripheral quantitative computed tomography (pQCT), biomechanical testing, and molecular biological analyses. Histologically, healing of the defect was characterized by filling of the medullary cavity with trabecular new bone during the first week of healing, and by closing of the cortical window by 6 weeks. Small areas of periosteal chondrogenesis were frequently observed during defect healing. In pQCT, bone mineral content (BMC) of the defect area approached that of intact control bone already by 3 weeks, reflecting the production of trabecular bone. Similarly, the bending strength and stiffness of the healing femur reached the level of intact control femur already at 3 weeks. Bone formation and remodeling was followed by Northern analyses, which demonstrated elevated mRNA levels for bone components (type I collagen and osteocalcin), and for osteoclastic enzymes (cathepsin K, matrix metalloproteinase-9, and tartrate-resistant acid phosphatase) throughout the healing period. Finally, the applicability of the defect model for gene therapy experiments was tested using adenovirus-mediated transfer of the LacZ reporter gene. Both histochemistry and mRNA analyses demonstrated that the gene was expressed in the repair tissue with the highest expression during the first week of healing. The present model thus provides a standardized environment for studies on induction and remodeling of trabecular new bone in normal and genetically engineered mice.

Effect of Experimental Diabetes and Growth Hormone Administration on the Strength of Colonic Anastomoses in Rats

The influence of growth hormone (GH; 2 mg/kg/day) administration on the mechanical breaking strength of colonic anastomoses in diabetic rats has been investigated on the day of operation (suture binding capacity) and after 4 and 7 days of healing. In diabetic rats, the suture binding capacity was decreased by 26% in both ultimate load and relative failure energy. After 4 days of healing, no difference was observed between control and diabetic animals. After 7 days, relative failure energy in the diabetic animals was reduced by 33%. GH administration to diabetic animals did not alter strength during the first week of healing. We found an increased circumference (33%) and defatted dry weight (22%) of the colon in diabetic rats. In conclusion, diabetes impairs the suture-binding capacity of the colon in rats, while there is only little influence on healing in the following week. GH administration could not influence the strength of colonic anastomoses in diabetic animals.

The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice.

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.

Low-dose ultrasound effects on wound healing: a controlled study with Yucatan pigs.

This study reports on the effect of low-dose ultrasound in accelerating wound healing in matched pairs of surgically induced incisions and full-thickness and partial-thickness lesions in 11 Yucatan mini-pigs after 7 days of healing and 5 days of sonation. Tensile strength, collagen deposition (hydroxyproline), reduction in wound size (full-thickness lesion), and mast-cell degranulation were significantly greater in the sonated lesions than in the sham-treated controls (p = 0.01). Sonation enhanced strength by 24% and collagen deposition by 29%, when compared with controls. There were no significant differences in the quality of healing as measured by an ordinal scale. The results suggest that within the first week of healing, low-dose ultrasound facilitates wound healing. More research is needed to confirm the most effective dose, frequency, and treatment duration and intervention time for maximum healing.