Agent-based modelling and parameter sensitivity analysis with a finite-element method for skin contraction

In this paper, we extend the model of wound healing by Boon et al. (J Biomech 49(8):1388–1401, 2016). In addition to explaining the model explicitly regarding every component, namely cells, signalling molecules and tissue bundles, we categorized fibroblasts as regular fibroblasts and myofibroblasts. We do so since it is widely documented that myofibroblasts play a significant role during wound healing and skin contraction and that they are the main phenotype of cells that is responsible for the permanent deformations. Furthermore, we carried out some sensitivity tests of the model by modifying certain parameter values, and we observe that the model shows some consistency with several biological phenomena. Using Monte Carlo simulations, we found that there is a significant strong positive correlation between the final wound area and the minimal wound area. The high correlation between the wound area after 4 days and the final/minimal wound area makes it possible for physicians to predict the most probable time evolution of the wound of the patient. However, the collagen density ratio at the time when the wound area reaches its equilibrium and minimum, cannot indicate the degree of wound contractions, whereas at the 4th day post-wounding, when the collagen is accumulating from null, there is a strong negative correlation between the area and the collagen density ratio. Further, under the circumstances that we modelled, the probability that patients will end up with 5% contraction is about 0.627.

     

Effects of cardiotonic steroids on dermal collagen synthesis and wound healing.

We previously reported that cardiotonic steroids stimulate collagen synthesis by cardiac fibroblasts in a process that involves signaling through the Na-K-ATPase pathway (Elkareh et al. Hypertension 49: 215-224, 2007). In this study, we examined the effect of cardiotonic steroids on dermal fibroblasts collagen synthesis and on wound healing. Increased collagen expression by human dermal fibroblasts was noted in response to the cardiotonic steroid marinobufagenin in a dose- and time-dependent fashion. An eightfold increase in collagen synthesis was noted when cells were exposed to 10 nM marinobufagenin for 24 h (P < 0.01). Similar increases in proline incorporation were seen following treatment with digoxin, ouabain, and marinobufagenin (10 nM x 24 h, all results P < 0.01 vs. control). The coadministration of the Src inhibitor PP2 or N-acetylcysteine completely prevented collagen stimulation by marinobufagenin. Next, we examined the effect of digoxin, ouabain, and marinobufagenin on the rate of wound closure in an in vitro model where human dermal fibroblasts cultures were wounded with a pipette tip and monitored by digital microscopy. Finally, we administered digoxin in an in vivo wound healing model. Olive oil was chosen as the digoxin carrier because of a favorable partition coefficient observed for labeled digoxin with saline. This application significantly accelerated in vivo wound healing in rats wounded with an 8-mm biopsy cut. Increased collagen accumulation was noted 9 days after wounding (both P < 0.01). The data suggest that cardiotonic steroids induce increases in collagen synthesis by dermal fibroblasts, as could potentially be exploited to accelerate wound healing.     

Temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction

Wound contraction can substantially reduce the amount of new tissue needed to reestablish organ integrity after tissue loss. Fibroblasts, rich in F-actin bundles, generate the force of wound contraction. Fibronectin-containing microfibrils link fibroblasts to each other and to collagen bundles and thereby provide transduction cables across the wound for contraction. The temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction have not been determined. To establish these relationships, we used a cutaneous gaping wound model in outbred Yorkshire pigs. Granulation tissue filled approximately 80% of the wound space by day 5 after injury while wound contraction was first apparent at day 10. Neither actin bundles nor fibronectin receptors were observed in 5-d wound fibroblasts. Although fibronectin fibrils were assembled on the surfaces of 5-d fibroblasts, few fibrils coursed between cells. Day-7 fibroblasts stained strongly for nonmuscle-type F-actin bundles consistent with a contractile fibroblast phenotype. These cells expressed fibronectin receptors, were embedded in a fibronectin matrix that appeared to connect fibroblasts to the matrix and to each other, and were coaligned across the wound. Transmission EM confirmed the presence of microfilament bundles, cell-cell and cell-matrix linkages at day 7. Fibroblast coalignment, matrix interconnections, and actin bundles became more pronounced at days 10 and 14 coinciding with tissue contraction. These findings demonstrate that granulation tissue formation, F-actin bundle and fibronectin receptor expression in wound fibroblasts, and fibroblast-matrix linkage precede wound contraction.     

A mathematical model for the simulation of the formation and the subsequent regression of hypertrophic scar tissue after dermal wounding

A continuum hypothesis-based model is presented for the simulation of the formation and the subsequent regression of hypertrophic scar tissue after dermal wounding. Solely the dermal layer of the skin is modeled explicitly and it is modeled as a heterogeneous, isotropic and compressible neo-Hookean solid. With respect to the constituents of the dermal layer, the following components are selected as primary model components: fibroblasts, myofibroblasts, a generic signaling molecule and collagen molecules. A good match with respect to the evolution of the thickness of the dermal layer of scars between the outcomes of simulations and clinical measurements on hypertrophic scars at different time points after injury in human subjects is demonstrated. Interestingly, the comparison between the outcomes of the simulations and the clinical measurements demonstrates that a relatively high apoptosis rate of myofibroblasts results in scar tissue that behaves more like normal scar tissue with respect to the evolution of the thickness of the tissue over time, while a relatively low apoptosis rate results in scar tissue that behaves like hypertrophic scar tissue with respect to the evolution of the thickness of the tissue over time. Our ultimate goal is to construct models with which the properties of newly generated tissues that form during wound healing can be predicted with a high degree of certainty. The development of the presented model is considered by us as a step toward their construction.     

Influence of initial collagen and cellular concentrations on the final surface area of dermal and skin equivalents: A box-behnken analysis

Summary Our laboratory has been involved in finding optimal conditions for producing dermal and skin equivalents. As an original approach, a Box-Behnken experimental design was used to study the effects of the initial collagen and fibroblast concentrations and the initial gel thickness on the contraction of dermal and skin equivalents. The final surface area of dermal equivalent varied significantly with the initial concentration of collagen and fibroblast, whereas the initial thickness of gel had no appreciable effect on the contraction of the dermal equivalent. When keratinocytes were grown on these dermal equivalents they produced a very severe contraction, to an extent that all skin equivalents had a similar final surface area. This severe contraction was independent of collagen and fibroblast concentrations. Models for the prediction of the final percentage contraction of dermal and skin equivalents as a function of the initial concentration of collagen, the logarithm of fibroblast concentration, and the initial gel thickness were obtained and analyzed. Keratinocytes grown at the lowest seeding density did not contract the equivalents. However, histologic analysis has shown an incomplete coverage by these cells of the equivalents. The extensive contraction of the skin equivalent presenting adequate morphology is a major drawback toward its clinical utilization for burn wound coverage. The financial supports for this project were received from Canadian NSERC postgraduate scholarship (P. Rompré), Québec FCAR postgraduate scholarship (C.A. López Valle), France-Québec research grant in Biotechnology (F.A. Auger), Canadian MRC grant (F.A. Auger), and NSERC grants (A. LeDuy and J. Thibault).     

Topical application of ALK5 inhibitor A-83-01 reduces burn wound contraction in rats by suppressing myofibroblast population

Burn scar contracture that follows the healing of deep dermal burns causes severe deformation and functional impairment. However, its current therapeutic interventions are limited with unsatisfactory outcomes. When we treated deep second-degree burns in rat skin with activin-like kinase 5 (ALK5) inhibitor A-83-01, it reduced wound contraction and enhanced the area of re-epithelialization so that the overall time for wound closing was not altered. In addition, it reduced myofibroblast population in the dermis of burn scar with a diminished deposition of its biomarker proteins such as α-SMA and collagen. Treatment of rat dermal fibroblast with A-83-01 inhibited transforming growth factor-β1 (TGF-β1)-dependent induction of α-SMA and collagen type I. Taken together, these results suggest that topical application of ALK5 inhibitor A-83-01 could be effective in preventing the contraction of burn wound without delaying the wound closure by virtue of its inhibitory activity against the TGF-β-induced increase of myofibroblast population.     

Comparison of hair dermal cells and skin fibroblasts in a collagen sponge for use in wound repair

The adult hair follicle has well-defined dermal and epithelial populations that display distinct developmental properties. The follicular dermal cells, namely the dermal papilla and dermal sheath, are derived from the same mesenchymal cells as dermal fibroblasts and therefore, we believed that follicular cells could be useful sources of interfollicular keratinocytes and fibroblast for skin wound repair. In this study, we evaluated the relative effect of various mesenchymal-derived cells on wound healing following skin injury. Human dermal cells, including two different follicular dermal cells and skin fibroblasts were cultured in collagen sponges and compared with respect to wound healing. Results indicated that there was no significant difference in wound contraction and angiogenesis among the cell types. Further, dermal sheath cells exhibited relatively poor results compared with other cells in new collagen synthesis. Finally, basement membrane reformation and new collagen synthesis for the dermal papilla cell grafts was superior to those of the dermal sheath cells or fibroblasts.     

Appearance of tenascin in healing skin of the mouse: possible involvement in seaming of wounded tissues

Distribution of the extracellular matrix glycoprotein tenascin during wound healing in mouse skin was studied immunohistochemically. Within 24 hours after wounding, and preceding the formation of granulation tissue, tenascin appeared in the basement membranes beneath epidermis and hair follicles adjacent to the wound edges and in the wounded edges of cutaneous muscle layer. Granulation tissue began to form in the wound space at about 1-2 days and was immediately covered by epidermis. Tenascin first appeared in the periphery of the granulation tissue beneath healing epidermis and around the wounded edges of cutaneous muscle layer. Then the tenascin-positive area extended into the inner region of granulation tissue. At about 5-7 days, all of the granulation tissue was intensely stained with anti-tenascin serum. Tenascin immunoreactivity decreased as granulation tissue was replaced with reconstructed dermal tissue at 7-14 days. In most cases, tenascin staining persisted longest in the dermis beneath the healing epidermis and at the juncture of healing edges of cutaneous muscle layer. It disappeared at about 10-14 days after wounding. These findings suggest that tenascin may play an important role in the seaming of wounded tissues.     

Effectiveness and Safety of the PEGT/PBT Copolymer Scaffold as Dermal Substitute in Scar Reconstruction Wounds (Feasibility Trial)

Skin defects left after excision of hypertrophic scars were treated with a dermal substitute and split-thickness skin grafts transplanted after vascularisation of the substitute. The used substitute was a synthetic porous scaffold made from the biodegradable copolymer polyethyleneglycol-terephtalate and polybuthylene-terephtalate. The study was designed to assess the rate of granulation tissue formation, graft take, and after 3 and 12 months the quality of life (pain, comfort of treatment, cosmetic or functional nuisance), scar formation and wound contraction. In addition, scaffold biodegradation and scar tissue formation were evaluated histologically. Seven patients with different causes of burn injury were enrolled, of which 5 completed the study. In the first 4 patients the time between scaffold application and split-thickness skin overgrafting was in between 17 and 24 days. The time point of overgrafting was significantly reduced to 10–12 days by meshing of the dermal scaffold as evidenced in the last 3 patients. Histological evaluation at 3 months revealed normal generation of dermal tissue, however, the collagen bundles were parallel organized like in scar tissue. In the deeper layers of the neodermis, fragments of the dermal substitute were present, causing a mild inflammatory response. One year post-treatment, some fragments of the copolymer were still observed. The extent of wound contraction after successful overgrafting ranged from 30% to 57% after 1 year. All 5 patients showed an improvement in the total Vancouver Scar Score compared to the value before scar removal being similar to what can be expected when treated with split-thickness skin grafts alone. No unanticipated adverse effects due to application of the substitute were observed. We conclude that although this synthetic dermal substitute can be safely used in humans, the presence of 3D dermal template in a full-thickness skin defect will not automatically improve the skin tissue regeneration process or inhibit wound contraction. This revised version was published online in July 2006 with corrections to the Cover Date.     

TGF-β1 induces the expression of type I collagen and SPARC,and enhances contraction of collagen gels,by fibroblasts from young and aged donors

Fibroblasts have a major role in the synthesis and reorganization of extracellular matrix that occur during wound repair. An impaired biosynthetic or functional response of these cells to stimulation by growth factors might contribute to the delayed wound healing noted in aging. We, therefore, compared the responses of dermal fibroblasts from young and elderly individuals (26, 29, 65, 89, 90, and 92 years of age) to transforming growth factor-β1 (TGF-β1) with respect to: (1) the synthesis of type I collagen and SPARC (two extracellular matrix proteins that are highly expressed by dermal fibroblasts during the remodeling phase of wound repair) and (2) the contraction of collagen gels, an in vitro assay of wound contraction. With the exception of one young donor, all cultures exposed for 44 hours to 10 ng/ml TGF-β1 exhibited a 1.6- to 5.5-fold increase in the levels of secreted type 1 collagen and SPARC, relative to untreated cultures, and exhibited a 2.0- to 6.2-fold increase in the amounts of the corresponding mRNAs. Moreover, the dose-response to TGF-β1 (0.1–10 ng/ml), as determined by synthesis of type I collagen and SPARC mRNA, was as vigorous in cells from aged donors as in cells from a young donor. In assays of collagen gel contraction, fibroblasts from all donors were stimulated to a similar degree by 10 ng/ml TGF-β1. In conclusion, cells from both young and aged donors exhibited similar biosynthetic and contractile properties with exposure to TGF-β1. It therefore appears that the impaired wound healing noted in the aged does not result from a failure of their dermal fibroblasts to respond to this cytokine. © 1994 Wiley-Liss, Inc.     

The structure of the osteoderms in the Gekko: Tarentola mauritanica

Histological and cytological analysis reveals that the osteoderms of Tarentola mauritanica are composed of an outer part superimposed on a basal region. The structure of both parts can be related to that of the surrounding dermis. The basal part of the osteoderms, inserted in the dense dermis, is made up of abundant closely packed collagen fibrils that orient the mineral deposit. The outer part, located in the superficial loose dermis, is crossed by few bundles of mineralized collagen fibrils arising from the basal part. These bundles connect the osteoderm to the overlying loose dermis. The outer superficial part is characterized by the presence of mineralized globules surrounding the mineralized collagen bundles. In these globules, the crystals are deposited on a microfibrillar matrix rich in acidic mucosubstances and composed of radially oriented, tangled microfilaments that lie among the collagen bundles. The two different mineralizing systems in the osteoderms of Tarentola mauritanica may reflect two different organic matrices. The mineral is deposited in a preexisting dermal tissue, as a "metaplastic ossification," and is another expression of the potential retained by the reptilian dermis to form mineralized structures.     

Topical application of aminopeptidase N-neutralizing antibody accelerates wound closure

Upon release from keratinocytes, 14-3-3 sigma (also known as stratifin) acts on the dermal fibroblast and modulates its production of extracellular matrix proteins. Subsequent to the recent identification as a receptor responsible for stratifin-mediated matrix turnover in dermal fibroblasts, aminopeptidase N has been implicated in the regulation of epidermal?Cdermal communication and expression of key matrix proteases and adhesion molecules. In light of the growing importance of aminopeptidase N in modulation of the fibroblast phenotype, the present study evaluates the potential of targeting the ectoenzyme in cutaneous repair, and demonstrates that neutralization of aminopeptidase N led to acceleration of wound closure. This was attributed to at least in part an increase of collagen deposition and fibroblast contractility in the granulation tissue. These findings confirmed the important role of aminopeptidase N in post-injury tissue remodeling and wound contraction.     

The twisted collagen network of the box-fish scutes

The present article describes the three-dimensional arrangement of collagen fibrils in dermal plates of different species of Ostraciidae. These dermal plates or 'scutes' are transformed scales, which have a polygonal shape and form a rigid tiling. They are natural composites, associating a fibrous network with a mineral deposit lying at two different levels of the scute, the 'ceiling' and the 'floor', plus a set of similarly mineralized walls joining the two levels. The three-dimensional structure of the collagen network can be compared to that of 'plywood': fibrils align parallel within superposed layers of uniform thickness, and their direction changes from layer to layer. In the dermal plate, two types of plywood have been evidenced: (1) one lying between the two mineralized plates, where the orientation of fibrils rotates continuously, and (2) one under the lower plate, with thick layers of fibrils, each showing a constant orientation, but abrupt angular changes are observed at the transition from one layer to the following one. In oblique sections, both types of plywood reveal large series of arced patterns, testifying to a twisted arrangement of collagen fibrils, analogous to the arrangement of molecules or polymers in cholesteric liquid crystals. The network is reinforced by some collagen fibrils running unidirectionally and almost normally to the lamellate structure. Moreover in the overall organization of the scute, these plywood systems form a set of nested boxes. This original architecture is compared to the arrangement of the collagenous network previously described in most fish scales and in other extracellular matrices.     

The rhinoceros among Serpents: Comparative anatomy and experimental biophysics of Calabar burrowing python (Calabaria reinhardtii) skin

The Calabar burrowing python (Calabaria reinhardtii) has a unique combination of marked thickness of the integumentary layers, a highly organized lamellate arrangement of the dermal collagen bundles, and a reduction in the size of the interscale hinge region of the integument. Biomechanical testing demonstrates that the skin of C. reinhardtii is more resistant to penetration than the skin of other snakes. The laminar arrangement of the collagen bundles provides for penetrative resistance, even while maintaining the flexibility characteristic of snake skin. Considering the life history of this species, it is hypothesized that the specialized integument of C. reinhardtii is a passive defensive mechanism against penetrative bites from maternal rodents and predators.     

Morphological evidence of basal keratinocyte migration during the re-epithelialization process

The regeneration of wounded stratified epithelium is accomplished via the migration of keratinocytes from the margins of the wound. However, the process of keratinocyte migration on the wound surface and the role of epithelial stem cells during re-epithelialization remain to be elucidated. Therefore, we administered BrdU to embryonic mice and generated epithelial defects on the buccal mucosa of these mice at two weeks after birth, using CO₂ laser irradiation, with which we removed the entire thickness of the epithelium. In the unwounded epithelium, cytokeratin 14, p63, and BrdU were localized within the basal layer of the epithelium, but the majority of cells within the regenerated epithelium were immunopositive for these proteins. PCNA-negative and BrdU-positive basal keratinocytes, which evidence a slow cell cycle, were localized solely within the basal layer of the unwound epithelium facing the tips of dermal papillae. After laser irradiation, these basal keratinocytes facing the tips of the papillae evidenced positive immunoreactivity for PCNA, in addition to BrdU. These results indicate that epithelial stem cells of oral mucosa may be localized in the basal layer of the epithelium facing the tips of dermal papillae, and may migrate laterally with other basal keratinocytes in response to external stimuli. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

胎盘间充质干细胞治疗小鼠烫伤愈合的相关研究

目的:观察胎盘间充质干细胞对TGF-β1/Smad信号通路的调控作用,探讨胎盘间充质干细胞对烫伤愈合及瘢痕形成的影响.方法:构建小鼠烫伤模型,注射人胎盘间充质干细胞(hPMSCs),荧光显微镜观察小鼠创伤皮肤组织中hPMSCs细胞的存活情况;HE和Masson染色观察小鼠创伤皮肤的变化;Western blot检测观察...     

Preparation and evaluation of a nonproprietary bilayer skin substitute.

Cross-linked, allogeneic, telopeptide-depleted dermal grafts were lyophilized and laminated with silicone rubber elastomer. Resultant bilayers were studied for incorporation into the wound site and capacity to inhibit cutaneous wound contraction in experimental animals. Bilateral full-thickness skin wounds were made in 20 male New Zealand white rabbits. One side was grafted with the processed graft, while the contralateral side remained ungrafted as a control wound. Over 63 days, wound sites were analyzed at intervals on the basis of the extent and rate of wound contraction and by histologic examination. Cutaneous wounds successfully incorporated graft matrix and were significantly inhibited in their rate and extent of wound contraction. Notably, by day 63, grafted wounds retained 71 percent of their original area, whereas ungrafted control wounds retained only 16 percent of their original area. There were no graft rejections, and the bilayer graft's dermal analogue appeared to function as a biodegradable template that physically conformed neodermis to a preestablished pattern while counteracting contractile forces. This investigation suggests that, in experimental animals, the success of bilayer dermal grafts is less dependent on highly specialized and complex preparative techniques than typically has been presumed and that relatively simple, previously published, nonproprietary techniques, when adapted to a bilayer format, yield acceptable results as defined in terms of biocompatibility, capacity for graft incorporation, and inhibition of wound contraction.     

微等离子束对豚鼠皮肤超微结构分析和羟脯氨酸测定

目的观察微等离子束对豚鼠皮肤胶原组织作用效应的组织学和超微结构变化及羟脯氨酸含量测定,探讨微等离子束的作用机理。方法选择15只豚鼠,每只豚鼠背部划分为实验侧和空白对照侧2个等分区域,给予60W/10 kJ微等离子束照射,于作用后即刻、1周后和1月后分别切取实验侧及空白对照部位皮肤行组织病理维多利亚-立春红染色,透射电镜分析和羟脯氨酸检测试剂盒进行含量测定。结果 60 W/10 kJ即刻表现为表皮局灶性出现点阵状改变,部分表皮出现汽化缺失或者坏死变性,真皮浅层胶原组织出现点阵化表现和明显均质化;特殊染色显示微等离子束主要影响真皮胶原纤维,形成局灶性胶原纤维凝集和变性。1周后皮肤浅层胶原组织结构逐渐致密,排列有序,有少量组织细胞。1月后皮肤浅层胶原组织明显增厚,胶原纤维增粗并排列致密,弹力纤维呈局灶性增粗。透射电镜显示微等离子束作用后表皮细胞较完整,细胞间结构正常,但真皮胶原丧失正常结构,细胞结构消失,大量细胞凋亡明显,1月后仍可见少量细胞凋亡的表现但胶原结构逐渐恢复,浅层胶原纤维排列明显致密。羟脯氨酸测定显示微等离子束作用1周后羟脯氨酸含量要高于作用之前,但是差异性不具有统计学意义（P〉0.05）;1月后羟脯氨酸含量要明显高于作用前,差异性具有统计学意义（P〈0.05）。结论微等离子束对豚鼠皮肤胶原组织作用有明显的刺激效应,其主要靶组织为真皮胶原组织,可以明显促进皮肤新生胶原的增生。     

Sensitivity and feasibility of a one-dimensional morphoelastic model for post-burn contraction

We consider a one-dimensional morphoelastic model describing post-burn scar contraction. Contraction can lead to a limited range of motion (contracture). Reported prevalence of burn scar contractures are 58.6% at 3–6 weeks and 20.9% at 12 months post-reconstructive surgery after burns. This model describes the displacement of the dermal layer of the skin and the development of the effective Eulerian strain in the tissue. Besides these components, the model also contains components that play a major role in the skin repair after trauma. These components are signaling molecules, fibroblasts, myofibroblasts, and collagen. We perform a sensitivity analysis for many parameters of the model and use the results for a feasibility study. In this study, we test whether the model is suitable for predicting the extent of contraction in different age groups. To this end, we conduct an extensive literature review to find parameter values. From the sensitivity analysis, we conclude that the most sensitive parameters are the equilibrium collagen concentration in the dermal layer, the apoptosis rate of fibroblasts and myofibroblasts, and the secretion rate of signaling molecules. Further, although we can use the model to simulate significant distinct contraction densities in different age groups, our results differ from what is seen in the clinic. This particularly concerns children and elderly patients. In children we see more intense contractures if the burn injury occurs near a joint, because the growth induces extra forces on the tissue. Elderly patients seem to suffer less from contractures, possibly because of excess skin.

     

Increased gelsolin expression and retarded collagen lattice contraction with smooth muscle cells from Crohn's diseased intestine

Intestinal smooth muscle cells (SMC) produce the fibrotic tissue, strictures, that characterize Crohn's disease. These SMC change their phenotype from a contractile muscle form to an inflammation-responsive form that migrates and synthesizes a collagen matrix. It is postulated that the inflammatory responsive SMC form associates differently with its surrounding collagen matrix compared to the normal SMC form. SMC derived from Crohn's diseased and uninvolved bowel were sustained in cell culture. Cultured SMC incorporated in collagen lattices have the capacity to reduce the size of that lattice, referred to as lattice contraction. At day 2, Crohn's SMC-populated collagen lattices were reduced to 21% of their initial area, while non-Crohn's SMC collagen lattices were reduced to 8%. Crohn's SMC demonstrate retarded lattice contraction compared to non-Crohn's SMC. When grown in monolayer culture, Crohn's-derived SMC cover 30% more area than non-Crohn's SMC. By Western blot analysis Crohn's SMC express more gelsolin, an actin-binding protein found elevated in cells exhibiting increased cell motility. Was the increased expression of gelsolin related to retarded collagen lattice contraction? Intracellular levels of gelsolin were elevated by the electroporation of plasma gelsolin protein into suspended non-Crohn's SMC. When incorporated in collagen lattices, gelsolin loaded cells showed retarded lattice contraction compared to SMC loaded with albumin. Crohn's SMC show increased expression of gelsolin, which may be associated with a diminished capacity to reorganize collagen fiber bundles. It is suggested that increased concentrations of gelsolin in Crohn's SMC is consistent with enhanced cell migration as a consequence of the inflammatory state of Crohn's diseased intestine.