Fluid handling performance of wound dressings tested in a robotic venous leg ulcer system under compression therapy.

We designed, developed, built, and utilised a robotic system of a leg with two venous leg ulcers for testing the fluid handling performance of three wound dressing types. The results showed that a foam-based dressing technology is inferior in fluid handling performance when applied to an exuding venous leg ulcer, such that the dressing needs to manage the exudate in a vertical configuration with respect to the ground, that is, so that gravity pulls the exudate to concentrate in a small region at the bottom of the dressing. Moreover, wound dressings containing superabsorbent polymers do not necessarily function equally in fluid handling for venous leg ulcer scenarios, as the extreme requirements from the dressing (to manage the viscous fluid of a vertical and typically highly-exuding wound) appear to distinguish between optimal and suboptimal product performances despite that the tested products contain a superabsorbent, theoretically lumping them together to belong to a so-called 'superabsorbent dressing category'. In other words, it is a false premise to categorise products from different manufacturers into families based on material contents, and then assume that their laboratory or clinical performance is equal, so that from this point they can be judged solely on the basis of price.

The biomechanical efficacy of a dressing with a soft cellulose fluff core in protecting prone surgical patients from chest injuries on the operating table.

Pressure ulcers are soft-tissue damage associated with tissue exposure to sustained deformations and stress concentrations. In patients who are proned for ventilation or surgery, such damage may occur in the superficial chest tissues that are compressed between the rib cage and the support surface. Prophylactic dressings have been previously proven as generally effective for pressure ulcer prevention. In this study, our goal was to develop a novel computational modelling framework to investigate the biomechanical efficacy of a dressing with a soft cellulose fluff core in protecting proned surgical patients from chest pressure ulcers occurring on the operating table, due to body fixation by the Relton-Hall frame. We compared the levels of mechanical compressive stresses developing in the soft chest tissues, above the sternum and ribs, due to the trunk weight, whilst the body is supported by the Relton-Hall frame pads, with versus without the prophylactically applied bilateral dressings. The protective efficacy index for the extremely high stresses, above the 95th-percentile, were 40.5%, 25.6% and 24.2% for skin, adipose and muscle, respectively, indicating that the dressings dispersed elevated soft-tissue stresses. The current results provide additional support for using soft cellulose fluff core dressings for pressure ulcer prophylaxis, including during surgery.

Fluid Handling Dynamics and Durability of Silver-Containing Gelling Fiber Dressings Tested in a Robotic Wound System.

OBJECTIVE: To develop a robotic phantom system containing multiple simulated wound replicates to determine the synergy in fluid absorbency and retention (sorptivity) performances and the post-simulated-use mechanical durability of silver-containing gelling fiber primary dressings when used with a secondary dressing, as per clinical practice. METHODS: Using a robotic system containing six identical wound simulators, the authors tested the sorptivity performances of the Exufiber Ag + (Mölnlycke Health Care, Gothenburg, Sweden) primary dressing (ExAg-polyvinyl alcohol [PVA]) against a market-leading comparator product, when used with a secondary foam dressing. The durability of the primary dressings after simulated use was further investigated through tensile mechanical testing. RESULTS: The ExAg-PVA primary dressing delivered greater fluid amounts for absorbency and retention by the secondary foam dressing, approximately 2- and 1.5-fold more than the comparator dressing pair after 10 and 15 hours, respectively. The ExAg-PVA dressing was also substantially less sensitive to the direction of pulling forces and, accordingly, exhibited post-use mechanical strength that was approximately four and six times greater than that of the other primary dressing (when the latter dressing was tested out-of-alignment with its visible seams) after 10 and 15 hours, respectively. CONCLUSIONS: The dynamics of the sorptivity and fluid sharing between primary and secondary dressings and the effect of directional preference of strength of the primary dressings for adequate durability, resulting in safe post-use removals, have been described. The comparative quantification of these capabilities should help clinical and nonclinical decision-makers select dressings that best meet their patient needs.

The performance of gelling fibre wound dressings under clinically relevant robotic laboratory tests.

The effectiveness of wound dressing performance in exudate management is commonly gauged in simple, non-realistic laboratory setups, typically, where dressing specimens are submersed in vessels containing aqueous solutions, rather than by means of clinically relevant test configurations. Specifically, two key fluid-structure interaction concepts: sorptivity-the ability of wound dressings to transfer exudate, including viscous fluids, away from the wound bed by capillary action and durability-the capacity of dressings to maintain their structural integrity over time and particularly, at removal events, have not been properly addressed in existing test protocols. The present article reviews our recent published research concerning the development of clinically relevant testing methods for wound dressings, focussing on the clinical relevance of the tests as well as on the standardisation and automation of laboratory measurements of dressing performance. A second objective of this work was to compile the experimental results characterising the performance of gelling fibre dressings, which were acquired using advanced testing methods, to demonstrate differences across products that apparently belong to the same "gelling fibre" family but differ remarkably in materials, structure and composition and, thereby, in performance.

Fluid management and strength postsimulated use of primary and secondary dressings for treating diabetic foot ulcers: Robotic phantom studies.

Non-offloaded diabetic heel ulcers and the wound dressings used to treat them may be subjected to considerable bodyweight forces. A novel robotic foot phantom with a diabetic heel ulcer was designed and constructed to test the combined performances of applied primary and secondary dressings, in simulated non-offloaded (standing) and offloaded (supine) postures. We specifically compared the performances of the primary Exufiber dressing (Mölnlycke Health Care) combined with the secondary Mepilex Border Flex dressing (Mölnlycke) against a corresponding pair from an alternative manufacturer. Fluid retention and distribution between the primary and secondary dressings of each pair were determined using weight tests, and mechanical strength of the primary dressings was further measured postsimulated use through tensile testing. The Exufiber and Mepilex Border Flex pair performed similarly in the two simulated postures (retention = ~97%), whereas the comparator pair exhibited a 13%-decrease in retention for a supine to standing transition. Furthermore, the Exufiber dressing delivered up to 2-times more fluid to its paired secondary dressing and endured 1.7-times greater strain energy than the corresponding primary dressing before failure occurred. The present robotic foot phantom and associated methods are versatile and suitable for testing any dressing, in consideration of the relevant clinical factors and practice.

Three-dimensional shape-conformation performances of wound dressings tested in a robotic sacral pressure ulcer phantom.

Effective exudate retention by dressings requires close and intimate dressing-wound contact, immediately and continuously after the dressing application. Any dressing-wound spaces may allow for build-up of non-retained fluids, causing exudate pooling which forms a favourable environment for pathogen growth. Maceration may follow if the pooled exudates spread to peri-wound skin. Dressings with a claimed 3D-shape-conformation technology are commercially available; however, their effectiveness in minimising dressing-wound gaps has never been scientifically investigated. We present a novel bioengineering methodology for testing the effectiveness of such 3D-shape-conformation dressings, using our recently reported robotic phantom system of a sacral pressure ulcer. By means of 3D laser scanning and bespoke software, we reconstructed dressing shapes after simulated use and calculated the goodness-of-fit between each dressing (swelled to near-saturation) and the corresponding wound geometry. Two dressing sizes (10 × 10 cm and 12.5 × 12.5 cm) and two wound depths (2.5 or 2 cm) were considered. All the tested dressings were far from reaching good contact with the (simulated) wounds: Approximately one-third of the wound volume and nearly half of the wound surface were not in contact with the swelled dressings. Our present findings question whether 3D-shape-conformation dressings are effective, by revealing their swelling behaviour which was previously unknown.

Simulation of the biomechanical effects induced by laser in situ keratomileusis (LASIK) for different levels of ablation in normal corneas.

PURPOSE: To employ a finite element (FE) stress model to simulate laser in situ keratomileusis (LASIK) surgery and its biomechanical consequences. METHODS: The basic geometrical model we used for the cornea was patient-specific on which we manually incorporated seven simulations: three simulations evaluating the effect of a 120, 140 and 180 µm flap (without ablation); three simulations evaluating ablation depths of 40, 80 and 120 µm (with a 120 µm flap); and one control model, without any simulated surgical intervention. RESULTS: In all simulations, stress values were greatest in the centre of the cornea. Furthermore, when comparing the different treatments, stress values were highest in the cornea with the deepest ablation, and were lowest in the non-treated cornea. Specifically, peak effective stresses were 0.031, 0.028 and 0.025 MPa in 120, 80 and 40 µm ablation depths, respectively. CONCLUSIONS: In our model, the depth of tissue penetration using ablation or flap creation was correlated with tissue loads-the thinner the residual stromal bed is, the greater are the stresses occurring as a result of the same IOP. RELEVANCE: We based our model geometry on patient specific scans, allowing for customisation of the treatment to the patient's corneal structure.

Critical biomechanical and clinical insights concerning tissue protection when positioning patients in the operating room: A scoping review.

An optimal position of the patient during operation may require a compromise between the best position for surgical access and the position a patient and his or her tissues can tolerate without sustaining injury. This scoping review analysed the existing, contemporary evidence regarding surgical positioning-related tissue damage risks, from both biomechanical and clinical perspectives, focusing on the challenges in preventing tissue damage in the constraining operating room environment, which does not allow repositioning and limits the use of dynamic or thick and soft support surfaces. Deep and multidisciplinary aetiological understanding is required for effective prevention of intraoperatively acquired tissue damage, primarily including pressure ulcers (injuries) and neural injuries. Lack of such understanding typically leads to misconceptions and increased risk to patients. This article therefore provides a comprehensive aetiological description concerning the types of potential tissue damage, vulnerable anatomical locations, the risk factors specific to the operative setting (eg, the effects of anaesthetics and instruments), the complex interactions between the tissue damage risk and the pathophysiology of the surgery itself (eg, the inflammatory response to the surgical incisions), risk assessments for surgical patients and their limitations, and available (including emerging) technologies for positioning. The present multidisciplinary and integrated approach, which holistically joins the bioengineering and clinical perspectives, is unique to this work and has not been taken before. Close collaboration between bioengineers and clinicians, such as demonstrated here, is required to revisit the design of operating tables, support surfaces for surgery, surgical instruments for patient stabilisation, and for surgical access. Each type of equipment and its combined use should be evaluated and improved where needed with regard to the two major threats to tissue health in the operative setting: pressure ulcers and neural damage.

High body mass index is a strong predictor of intraoperative acquired pressure injury in spinal surgery patients when prophylactic film dressings are applied: A retrospective analysis prior to the BOSS Trial.

We reported the efficacy of soft silicone multilayered foam dressings in preventing intraoperatively acquired pressure injuries (IAPIs) in the prone position using a Relton-Hall frame (BOSS trial). The aim of this study was to clarify the incidence and extract the risk factors for IAPIs in cases in which polyurethane film dressing was used against IAPIs before the BOSS trial period. This study conducted as a retrospective dual-center cohort study between August 2014 and Jun 2015 using the medical records in the operating room. The incidence of IAPIs that developed within 24 hours after surgery was 7.1% (7/99). The multivariate logistic regression analysis revealed that body mass index (BMI) (P = .0016, odds ratio [OR]: 1.22, 95% confidence interval (CI) 1.08-1.4) and length of surgery (P < .0001, OR 2.47, 95% CI 1.86-3.51) were independently associated with the development of IAPIs. Since high BMI was not extracted in BOSS trial, we conclude that the application of soft silicone multilayer foam dressings is important for preventing the development of IAPIs in patients with high BMI values.

Release of sodium pyruvate from sacral prophylactic dressings: A computational model.

The use of sacral dressings for pressure ulcer prevention is growing rapidly. In addition to their passive biomechanical role in pressure and shear reduction, in the near future, prophylactic dressings may also provide active tissue protection by releasing preventive agents or drugs into skin and deeper tissues. We investigated delivery of sodium pyruvate (NaPy) from an active dressing to potentially protect the sacral skin and underlying tissues in addition. We used four finite element model variants describing different skin roughness levels to determine time profiles of NaPy diffusion from the dressing into the skin layers. The NaPy concentrations for the different modelled cases stabilised after 1 to 6.5 hours from the time of application of the dressings, at 1% to 3% of the NaPy concentration in the dressing reservoir, which is considered potent. We conclude that prophylactic sacral dressings have the potential to deliver NaPy into skin and subdermally, to potentially increase soft tissue tolerance to sustained bodyweight-caused cell and tissue deformations. The time durations to achieve the steady-state potent NaPy dermal concentrations are clinically feasible, for example, for preparation of patients for surgery or for use in intensive care units.

Effect of laser therapy on expression of angio- and fibrogenic factors, and cytokine concentrations during the healing process of human pressure ulcers.

Objective: To evaluate the effect of laser irradiation at different wavelengths on the expression of selected growth factors and inflammatory mediators at particular stages of the wound healing process. Methods: Sixty-seven patients were recruited, treated, and analyzed (group A - 940 nm: 17 patients; group B - 808 nm: 18 patients; group C - 658 nm: 16 patients; group D - sham therapy: 17 patients). Patients received a basic treatment, including repositioning and mobilization, air pressure mattress and bed support surfaces, wound cleansing and drug therapy. Additionally, patients received laser therapy once a day, 5 times a week for 1 month in use of a semiconductor lasers (GaAlAs) which emitted a continuous radiation emission at separate wavelengths of 940 nm (group A), 808 nm (group B) and 658 nm (group C). In group D (sham therapy), laser therapy was applied in the same manner, but the device was off during each session (only the applicator was switched on to scan pressure ulcers using none coherent red visible light). Results: The positive changes in the measured serum (IL-2, IL-6 and TNF-α) and wound tissue (TNF-α, VEGF and TGFß1) parameters appeared to be connected only with the wavelength of 658 nm. The significant change in pro-inflammatory mediator levels [interleukin 2 (IL-2) with p=0.008 and interleukin 6 (IL-6) with p=0.016] was noticed after two weeks of laser therapy. In the other groups, the inflammation was also reduced, but the process was not as marked as in group C. Similarly, in the case of tumor necrosis factor (TNF-α) concentration, where after two weeks of treatment with irradiation at a wavelength of 658 nm, a rapid suppression was observed (p=0.001), whereas in the other groups, these results were much slower and not as obvious. Interestingly, again in the case of group C, the change in TNF-α concentration in wound tissue was most intensive (≈75% reduction), whereas the changes in other groups were not as obvious (≈50% reduction). After irradiation (658 nm), the VEGF expression increased significantly within the first two weeks, and then it decreased and maintained a stable level. In contrast, the TGFß1 activity remained level, but always higher in comparison to other groups Conclusions: The effective healing of pressure ulcers is connected with laser irradiation at a wavelength of 658 nm. We believe that this effect is related to the inhibition of inflammatory processes in the wound and stimulation of angiogenesis and fibroblast proliferation at this specific radiation (based both on concentration of interleukins and TNF-α serum level and VEGF, TGFß1, TNF-α activities in wound biopsies). Laser therapy at wavelengths of 940 and 808 nm does not significantly affect the above-mentioned repair processes, which explains its low effectiveness in the treatment of pressure ulcers.

Penile compression clamps: A model of the internal mechanical state of penile soft tissues.

AIMS: Prostate cancer is the most frequently diagnosed male cancer and urinary incontinence represents a major consequence following surgery. Penile compression clamps (PCCs) which externally occlude the urethra may be used to manage the incontinence. Despite potential complication of PCCs, such as deformation-inflicted tissue damage, to date, there are no reported biomechanical criteria for design of PCCs, in terms of quantitative parameters for evaluating the safety-versus-efficacy of existing or future designs. METHODS: We developed a set of computational three-dimensional models of the penis, to which compression was applied using five generic PCC designs. The internal mechanical states of the soft tissues of the penis were then analysed using finite element simulations. RESULTS: Stresses in skin, fat, and tunica albuginea regularly exceeded 10 kPa (75 mmHg). Cuff-type and knurl-type PCCs pose the highest potential risks to tissue health with elevated tissue stresses around the entire penile perimeter (cuff) or urethral stress concentrations (knurl). The soft and contoured PCCs produced the lowest values of these mechanical parameters. CONCLUSIONS: The present study identified design characteristics, including envelopment, adaptability, and durability which provide the safest mechanical conditions in the penis and thus minimize the risk of tissue damage while still managing incontinence. Such data should help to design a safer clamp.

Extensive Characterization and Comparison of Endothelial Cells Derived from Dermis and Adipose Tissue: Potential Use in Tissue Engineering.

Tissue-engineered constructs need to become quickly vascularized in order to ensure graft take. One way of achieving this is to incorporate endothelial cells (EC) into the construct. The adipose tissue stromal vascular fraction (adipose-SVF) might provide an alternative source for endothelial cells as adipose tissue can easily be obtained by liposuction. Since adipose-EC are now gaining more interest in tissue engineering, we aimed to extensively characterize endothelial cells from adipose tissue (adipose-EC) and compare them with endothelial cells from dermis (dermal-EC). The amount of endothelial cells before purification varied between 4-16% of the total stromal population. After MACS selection for CD31 positive cells, a >99% pure population of endothelial cells was obtained within two weeks of culture. Adipose- and dermal-EC expressed the typical endothelial markers PECAM-1, ICAM-1, Endoglin, VE-cadherin and VEGFR2 to a similar extent, with 80-99% of the cell population staining positive. With the exception of CXCR4, which was expressed on 29% of endothelial cells, all other chemokine receptors (CXCR1, 2, 3, and CCR2) were expressed on less than 5% of the endothelial cell populations. Adipose-EC proliferated similar to dermal-EC, but responded less to the mitogens bFGF and VEGF. A similar migration rate was found for both adipose-EC and dermal-EC in response to bFGF. Sprouting of adipose-EC and dermal-EC was induced by bFGF and VEGF in a 3D fibrin matrix. After stimulation of adipose-EC and dermal-EC with TNF-α an increased secretion was seen for PDGF-BB, but not uPA, PAI-1 or Angiopoietin-2. Furthermore, secretion of cytokines and chemokines (IL-6, CCL2, CCL5, CCL20, CXCL1, CXCL8 and CXCL10) was also upregulated by both adipose- and dermal-EC. The similar characteristics of adipose-EC compared to their dermal-derived counterpart make them particularly interesting for skin tissue engineering. In conclusion, we show here that adipose tissue provides for an excellent source of endothelial cells for tissue engineering purposes, since they are readily available, and easily isolated and amplified.

The Influence of Chronic Wound Extracts on Inflammatory Cytokine and Histatin Stability.

Chronic ulcers represent a major health burden in our society. Despite many available therapies, a large number of ulcers do not heal. Protein based therapies fail in part due to proteolytic activity in the chronic wound bed. The aim of this in vitro study was to determine whether typical inflammatory cytokines and human salivary histatins remain stable when incubated with chronic wound extracts. Furthermore we determined whether a short exposure of histatins or cytokines was sufficient to exert long term effects on fibroblast migration. Stability of human recombinant cytokines IL-6 and CXCL8, and histatin variants (Hst1, Hst2, cyclic Hst1, minimal active domain of Hst1) in the presence of chronic wound extracts isolated from non-healing ulcers, was monitored by capillary zone electrophoresis. Migration-stimulating activity was assessed using a dermal fibroblast wound healing scratch assay. Histatins and cytokines stayed stable in saline for > 24 h at 37°C, making them ideal as an off-the-shelf product. However, incubation with chronic wound extracts resulted in serious breakdown of Hst1 and Hst2 (~50% in 8 h) and to lesser extent cyclic Hst1 and the minimal active domain of Hst1 (~20% in 8 h). The cytokines IL-6 and CXCL8 were more stable in chronic wound extracts (~40% degradation in 96 h). An initial 8-hour pulse of histatins or cytokines during a 96-hour study period was sufficient to stimulate fibroblast migration equally well as a continuous 96-hour exposure, indicating that they may possibly be used as novel bioactive therapeutics, exerting their activity for up to four days after a single exposure.

A phase-contrast microscopy-based method for modeling the mechanical behavior of mesenchymal stem cells.

We present three-dimensional (3D) finite element (FE) models of single, mesenchymal stem cells (MSCs), generated from images obtained by optical phase-contrast microscopy and used to quantify the structural responses of the studied cells to externally applied mechanical loads. Mechanical loading has been shown to affect cell morphology and structure, phenotype, motility and other biological functions. Cells experience mechanical loads naturally, yet under prolonged or sizable loading, damage and cell death may occur, which motivates research regarding the structural behavior of loaded cells. For example, near the weight-bearing boney prominences of the buttocks of immobile persons, tissues may become highly loaded, eventually leading to massive cell death that manifests as pressure ulcers. Cell-specific computational models have previously been developed by our group, allowing simulations of cell deformations under compressive or stretching loads. These models were obtained by reconstructing specific cell structures from series of 2D fluorescence, confocal image-slices, requiring cell-specific fluorescent-staining protocols and costly (confocal) microscopy equipment. Alternative modeling approaches represent cells simply as half-spheres or half-ellipsoids (i.e. idealized geometries), which neglects the curvature details of the cell surfaces associated with changes in concentrations of strains and stresses. Thus, we introduce here for the first time an optical image-based FE modeling, where loads are simulated on reconstructed 3D geometrical cell models from a single 2D, phase-contrast image. Our novel modeling method eliminates the need for confocal imaging and fluorescent staining preparations (both expensive), and makes cell-specific FE modeling affordable and accessible to the biomechanics community. We demonstrate the utility of this cost-effective modeling method by performing simulations of compression of MSCs embedded in a gel.

Analytical and computational modeling of early penetration of non-enveloped icosahedral viruses into cells.

BACKGROUND: As obligate intracellular parasites, all viruses penetrate target cells to initiate replication and infection. OBJECTIVE: This study introduces two approaches for evaluating the contact loads applied to a cell during early penetration of non-enveloped icosahedral viruses. METHODS: The first approach is analytical modeling which is based on Hertz's theory for the contact of two elastic bodies; here we model the virus capsid as a triangle and the cell as an order-of-magnitude larger sphere. The second approach is finite element modeling, where we simulate three types of viruses: adeno-, papilloma- and polio- viruses, each interacting with a cell section. RESULTS: We find that the peak contact pressures and forces generated at the initial virus-cell contact depend on the virus geometry - that is both size and shape. With respect to shape, we show that the icosahedral virus shape induces greater peak pressures compared to a spherical virus shape. With respect to size, it is shown that the larger the virus is the greater are the contact loads in the attacked cell. CONCLUSION: Utilization of our modeling can be substantially useful not only for basic science studies, but also in other, more applied fields, such as in the field of gene therapy, or in `phage' virus studies.

Tissue loads applied by a novel medical device for closing large wounds.

Closure of large soft tissue defects following surgery or trauma as well as closure of large chronic wounds constitutes substantial but common reconstructive challenges. In such cases, an attempt to use conventional suturing will result in high-tension closure, therefore alternative external skin stretching systems were developed. These types of devices were meant to reduce local mechanical loads in the skin and the underlying tissues, taking advantage of the viscoelastic properties of the skin, especially mechanical creep, for primary wound closure. Studies have shown the clinical advantages of skin stretching systems, however, quantitative bioengineering models, demonstrating closure of large wounds, are lacking. Here we present finite element (FE) modeling of the TopClosure(®) tension relief system (TRS) and its biomechanical efficacy in three (real) wound cases, compared with the alternative of a conventional surgical suturing closure technique. Our simulations showed that peak effective stresses on the skin were at least an order of magnitude greater (and sometimes nearly 2 orders-of-magnitude greater) when tension sutures were used with respect to the corresponding TRS data. For the tension suture simulations, the tensile stress was in the range of 415-648 MPa and in the TRS simulations, it was 16-30 MPa. Based on the present computational FE modeling, the TRS reduces localized tissue deformations and stress concentrations in skin and underlying tissues while closing large wounds, compared to the deformations and stresses that are inflicted during the process of suturing. This substantial reduction of loads allows surgeons to better employ the viscoelastic properties of the skin for primary wound closure.

Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.

Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation.

Mechanical cytoprotection: A review of cytoskeleton-protection approaches for cells.

We review a class of cutting-edge approaches for cytoprotection of cells exposed to assaults such as sustained deformations, chemotherapy, radiotherapy, or ischemia. These approaches will enhance cell survival by mechanically protecting the structure and dynamics of the actin cytoskeleton (CSK). Cortical actin provides structural support to the plasma membrane (PM), protecting its integrity. Consequently, assaults can fragment the actin cortex leading to local, mechanical failure of the PM and poration of the cell. This disrupts normal trafficking of biomolecules across the PM, leading to loss of homeostasis and eventually, to cell death and tissue necrosis. Two different approaches to cytoskeletal protection are covered in this review paper. The first is to supply energy-related molecules to maintain and enhance the energy-consuming dynamics of the actin CSK. The second is to stabilize newly formed actin CSK directly¸ for example through cross-linking or reinforcement at PM anchoring sites. Research in this area is clearly still in its infancy. Very few studies have gone beyond characterizing the effects of induced damage to the actin CSK (and subsequent PM collapse). Recent work, focusing instead on sustaining the actin under non-physiological or pathophysiological conditions, has shown great promise. Such cytoskeletal-protection may find medical applications in preventing or minimizing tissue damage when tissues are unhealthy or at risk, or in enhancing cell performance under stress. Here, we condense the relevant cell biology and biomechanics background, assess candidate cytoskeletal protective agents, and review published works that have shown potential for medical benefit in experimental model systems.

A new technique for studying directional cell migration in a hydrogel-based three-dimensional matrix for tissue engineering model systems.

Cell migration has a key role in biological processes, e.g. malignancy, wound healing, immune response and morphogenesis. Studying migration and factors that influence it is beneficial, e.g. for developing drugs to suppress metastasis, heal wounds faster or enhance the response to infection. Though the majority of the literature describes two-dimensional (2D) migration studies in culture dishes, a more realistic approach is to study migration in three-dimensional (3D) constructs. However, simple-to-implement, straight-forward standardized quantitative techniques for analysis of migration rates of cell colonies in 3D are still required in the field. Here, we describe a new model system for quantifying directional migration of colonies in a hyaluronic acid (oxi-HA) and adipic acid dihydrazide (ADH) hydrogel-based 3D matrix. We further demonstrate that our previously reported image processing technique for measuring migration in 2D (Topman et al., 2011, 2012) is extendable for analyzing the rates of migration of cells that directionally migrate in the hydrogel and are fluorescently stained with a 4',6-diamidino-2-phenylindole (DAPI) nuclear stain. Together, the present experimental setup and image processing algorithm provide a standard test bench for measuring migration rates in a fully automated, robust assay which is useful for high-throughput screening in large-scale drug evaluations, where effects on migration in a 3D matrix are sought.