A Two-Experiment Approach to Scaling in Biomechanics.

A new approach to scaled experimentation has recently appeared in the open literature where hitherto unknown similitude rules have been discovered. The impact of this discovery on biomechanics is the focus of this paper, where rules for one and two scaled experiments are assessed. Biomechanical experimentation is beset by problems that can hinder its successful implementation. Availability of resources, repeatability and variability of specimens, ethical compliance and cost are the most prominent. Physical modeling involving synthetic composite materials can be used to advantage and circumvent ethical concerns but is presently impeded by cost and the limited scope of standardized geometries. The increased flexibility of the new approach, combined with the application of substantially cheaper three-dimensional printed materials, is investigated here for bone biomechanical experiments consisting of mechanical tests for the validation of finite element models by means of digital image correlation. The microstructure of the scaled materials is analyzed using a laser confocal microscope followed by the construction and validation of numerical models by means of a Bland-Altman statistical analysis. Good agreement is obtained demonstrated with means under 18 microstrains (µÏµ) and limits of agreement below 83 µÏµ. Consequently, numerical results for the new similitude approach shows an average percentage error of 3.1% and 4.8% for the optimized results across all values. The two-scaled experiment approach results in a sevenfold improvement for the average difference values of strain when compared to the single-scaled experiment, so demonstrating the potential of the new approach.

Zeroth-order finite similitude and scaling of complex geometries in biomechanical experimentation.

Scaled experimentation provides an alternative approach to full-scale biomechanical (and biological) testing but is known to suffer from scale effects, where the underlying system behaviour changes with scale. This phenomenon is arguably the overriding principal obstacle to the many advantages that scaled experimentation provides. These include reduced costs, materials and time, along with the eschewal of ethical compliance concerns with the application of substitute artificial materials as opposed to the use of hazardous biological agents. This paper examines the role scale effects play in biomechanical experimentation involving strain measurement and introduces a formulation that overtly captures scale dependencies arising from geometrical change. The basic idea underpinning the new scaling approach is the concept of space scaling, where a biomechanical experiment is scaled by the metaphysical mechanism of space contraction. The scaling approach is verified and validated with finite-element (FE) models and actual physical-trial experimentation using digital image correlation software applied to synthetic composite bone. The experimental design aspect of the approach allows for the selection of three-dimensional printing materials for trial-space analysis in a complex pelvis geometry. This aspect takes advantage of recent advancements in additive manufacturing technologies with the objective of countering behavioural distorting scale effects. Analysis is carried out using a laser confocal microscope to compare the trial and physical space materials and subsequently measured using surface roughness parameters. FE models were constructed for the left hemipelvis and results show similar strain patterns (average percentage error less than 10%) for two of the three trial-space material combinations. A Bland-Altman statistical analysis shows a good agreement between the FE models and physical experimentation and a good agreement between the physical-trial experimentation, providing good supporting evidence of the applicability of the new scaling approach in a wider range of experiments.

Performance evaluation of surgical techniques for treatment of scapholunate instability in a type II wrist.

We investigated the performance of three tenodesis techniques, modified Brunelli, Corella, and scapholunate axis (SLAM) methods in repairing scapholunate interosseous ligament (SLIL) disruption for a type II wrist using finite element-based virtual surgery and compared the results with those of a previous investigation for a type I wrist. In addition, a comparison of the carpal mechanics of type I and type II wrists was undertaken in order to elucidate the difference between the two types. For the type II wrist, following simulated SLIL disruption, the Corella reconstruction technique provided a superior outcome, restoring dorsal gap, volar gap, and SL angle to within 3.5%, 7.1%, and 8.4%, respectively, of the intact wrist. Moreover, application of the ligament reconstruction techniques did not significantly alter the motion pattern of the type II and type I wrists. For the type I wrist, SLIL disruption resulted in no contact between scaphoid-lunate cartilage articulation, whereas for the type II wrist, some contact was maintained. We conclude that the Corella ligamentous reconstruction technique is best able to restore SL gap, angle, and stability following SL ligament injury for both type II and type I wrists and is able to do so without altering wrist kinematics. Our findings also support the view that type I wrists exhibit row behaviour and type II wrists column behaviour. In addition, our analysis suggests that the extra articulation between the lunate and hamate in a type II wrist may help improve stability following SL ligament injury.

Effect of Femoral Head Size, Subject Weight, and Activity Level on Acetabular Cement Mantle Stress Following Total Hip Arthroplasty.

In cases where cemented components are used in total hip arthroplasty, damage, or disruption of the cement mantle can lead to aseptic loosening and joint failure. Currently, the relationship between subject activity level, obesity, and prosthetic femoral head size and the risk of aseptic loosening of the acetabular component in cemented total hip arthroplasty is not well understood. This study aims to provide an insight into this. Finite element models, validated with experimental data, were developed to investigate stresses in the acetabular cement mantle and pelvic bone resulting from the use of three prosthetic femoral head sizes, during a variety of daily activities and one high impact activity (stumbling) for a range of subject body weights. We found that stresses in the superior quadrants of the cortical bone-cement interface increased with prosthetic head size, patient weight, and activity level. In stumbling, average von Mises stresses (22.4 MPa) exceeded the bone cement yield strength for an obese subject (143 kg) indicating that the cement mantle would fail. Our results support the view that obesity and activity level are potential risk factors for aseptic loosening of the acetabular component and provide insight into the increased risk of joint failure associated with larger prosthetic femoral heads. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1771-1783, 2019.

Validation of biofilm formation on human skin wound models and demonstration of clinically translatable bacteria-specific volatile signatures.

Biofilms are major contributors to delayed wound healing and there is a need for clinically relevant experimental models to assess theranostics. Microorganisms release volatile organic compounds (VOCs) and the ability to identify these in infected cutaneous wounds could lead to efficient non-invasive diagnosis. The aims here were to develop and assess bacterial biofilm formation and identify their VOC profiles in an in vitro model and validate in human ex vivo incisional and excisional cutaneous wound models. Biofilm development was assessed using multiple microscopy techniques with biofilm-forming deficient controls and quantified using metabolic and biomass assays; and VOC production measured by gas chromatography-mass spectrometry. The production of most VOCs was affected by biofilm development and model used. Some VOCs were specific either for planktonic or biofilm growth. The relative abundance of some VOCs was significantly increased or decreased by biofilm growth phase (P < 0.05). Some Staphylococcus aureus and Pseudomonas aeruginosa VOCs correlated with biofilm metabolic activity and biomass (R ≤ -0.5; ≥0.5). We present for the first time bacterial biofilm formation in human ex vivo cutaneous wound models and their specific VOC profiles. These models provide a vehicle for human skin-relevant biofilm studies and VOC detection has potential clinical translatability in efficient non-invasive diagnosis of wound infection.

Scaling in biomechanical experimentation: a finite similitude approach.

Biological experimentation has many obstacles: resource limitations, unavailability of materials, manufacturing complexities and ethical compliance issues; any approach that resolves all or some of these is of some interest. The aim of this study is applying the recently discovered concept of finite similitude as a novel approach for the design of scaled biomechanical experiments supported with analysis using a commercial finite-element package and validated by means of image correlation software. The study of isotropic scaling of synthetic bones leads to the selection of three-dimensional (3D) printed materials for the trial-space materials. These materials conforming to the theory are analysed in finite-element models of a cylinder and femur geometries undergoing compression, tension, torsion and bending tests to assess the efficacy of the approach using reverse scaling of the approach. The finite-element results show similar strain patterns in the surface for the cylinder with a maximum difference of less than 10% and for the femur with a maximum difference of less than 4% across all tests. Finally, the trial-space, physical-trial experimentation using 3D printed materials for compression and bending testing provides a good agreement in a Bland-Altman statistical analysis, providing good supporting evidence for the practicality of the approach.

Cement interface and bone stress in total hip arthroplasty: Relationship to head size.

The use of larger prosthetic femoral heads in total hip arthroplasty (THA) has increased considerably in recent years in response to the need to improve joint stability and reduce risk of dislocation. However, data suggests larger femoral heads are associated with higher joint failure rates. For cemented implants, ensuring the continued integrity of the cement mantle is key to long term fixation. This paper describes an investigation into the effect of variation in femoral head size on stresses in the acetabular cement mantle and pelvic bone. Three commonly used femoral head sizes: 28, 32, and 36 mm diameter were investigated. The study was undertaken using a finite element model validated using surface strains obtained from Digital Image Correlation (DIC) during experimentation on a composite hemipelvis implanted with a cemented all-polyethylene acetabular cup. Following validation, the models were used to investigate stresses in the pelvic bone and acetabular cement mantle resulting from two loading scenarios; an average weight subject (700 N) and an overweight subject (1,000 N) undertaking a single leg stand. We found that the highest peak stresses occurred in the anterosuperior and posterosuperior regions of the bone-cement interface, in the line of action of the load, where debonding usually initiates. Stress on the cortical bone-cement interface increased with femoral head diameter by up to 9% whilst stresses in the trabecular bone remained relatively invariant. Our findings may help to explain higher joint failure rates associated with larger femoral heads. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2966-2977, 2018.

Evaluation of the performance of three tenodesis techniques for the treatment of scapholunate instability: flexion-extension and radial-ulnar deviation.

Chronic scapholunate ligament (SL) injuries are difficult to treat and can lead to wrist dysfunction. Whilst several tendon reconstruction techniques have been employed in the management of SL instability, SL gap reappearance after surgery has been reported. Using a finite element model and cadaveric study data, we investigated the performance of the Corella, scapholunate axis (SLAM) and modified Brunelli tenodesis (MBT) techniques. Scapholunate dorsal and volar gap and angle were obtained following virtual surgery undertaken using each of the three reconstruction methods with the wrist positioned in flexion, extension, ulnar deviation and radial deviation, in addition to the ulnar-deviated clenched fist and neutral positions. From the study, it was found that, following simulated scapholunate interosseous ligament rupture, the Corella technique was better able to restore the SL gap and angle close to the intact ligament for all wrist positions investigated, followed by SLAM and MBT. The results suggest that for the tendon reconstruction techniques, the use of multiple junction points between scaphoid and lunate may be of benefit. Graphical abstract The use of multiple junction points between scaphoid and lunate may be of benefit for tendon reconstruction techniques.

Volatile organic compound detection as a potential means of diagnosing cutaneous wound infections.

Chronic cutaneous wound infections and surgical site infections (SSIs) present a huge burden on the healthcare system and can lead to increased morbidity and mortality. Current diagnostic methods of identifying and confirming infection involve culture-based and molecular methods. Both techniques are time-consuming and delays commonly lead to untargeted empirical treatment. An ideal diagnostic method would be noninvasive and highly sensitive and detect pathogenic organisms with a high degree of accuracy to allow targeted treatment. Volatile organic compounds (VOCs) are a diverse group of carbon-based molecules produced and released by humans and microorganisms. VOC detection has the potential in aiding cutaneous wound infection diagnostics using noninvasive and time-efficient methods. This review provides a comprehensive update on VOCs produced and emitted by bacteria commonly associated with chronic wounds and SSIs. VOC sampling has the advantage of being painless, time-efficient, noninvasive, and reproducible. VOCs emitted by these organisms are diverse. In vitro studies have identified potential signature volatile profiles, which can be used in detecting these microorganisms. Combining these profiles with volatile profiles emitted from acute, chronic and surgical wounds in vivo could potentially allow identification of bacterial-specific VOCs. VOC detection has the potential for a relatively inexpensive, portable, noninvasive, and reliable clinical diagnostic tool, which could be used in detecting cutaneous wound infections and guiding their optimal management.

Analysis of tenodesis techniques for treatment of scapholunate instability using the finite element method.

Chronic scapholunate ligament (SL) injury is a common disorder affecting the wrist. Despite advances in surgical techniques used to treat this injury, SL gap re-emergence may occur postoperatively. This paper presents an investigation into the performance of the Corella, schapolunate axis (SLAM), and modified Brunelli tenodesis (MBT) surgical reconstruction techniques used to treat scapholunate instability. Finite element (FE) models were used to undertake virtual surgery, and the resulting scapholunate (SL) gap and angle obtained using the 3 techniques were compared. The Corella technique was found to achieve the SL gap and angle closest to the intact (ligament) wrist, restoring SL gap and angle to within 5.6% and 0.6%, respectively. The MBT method resulted in an SL gap least close to the intact. The results of our study indicate that the contribution of volar scapholunate interosseous ligament to scapholunate stability could be important.

3-D computer modelling of malunited posterior malleolar fractures: effect of fragment size and offset on ankle stability, contact pressure and pattern.

BACKGROUND: The positioning of the fracture fragment of a posterior malleolus fracture is critical to healing and a successful outcome as malunion of a posterior malleolar fracture, a condition seen in clinical practice, can affect the dynamics of the ankle joint, cause posterolateral rotational subluxation of the talus and ultimately lead to destruction of the joint. Current consensus is to employ anatomic reduction with internal fixation when the fragment size is larger than 25 to 33% of the tibial plafond. METHODS: A 3-dimensional finite element (FE) model of ankle was developed in order to investigate the effect of fragment size (6-15 mm) and offset (1-4 mm) of a malunited posterior malleolus on tibiotalar joint contact area, pressure, motion of joint and ligament forces. Three positions of the joint were simulated; neutral position, 20° dorsiflexion and 30° plantarflexion. RESULTS: Compared to the intact joint our model predicted that contact area was greater in all malunion scenarios considered. In general, the joint contact area was affected more by section length than section offset. In addition fibula contact area played a role in all the malunion cases. CONCLUSIONS: We found no evidence to support the current consensus of fixing posterior malleolus fractures of greater than 25% of the tibial plafond. Our model predicted joint instability only with the highest level of fracture in a loaded limb at an extreme position of dorsiflexion. No increase of peak contact pressure as a result of malunion was predicted but contact pattern was modified. The results of our study support the view that in cases of posterior malleolar fracture, posttraumatic osteoarthritis occurs as a result of load on areas of cartilage not used to loading rather than an increase in contact pressure. Ankle repositioning resulted in increased force in two ankle ligaments. Our finding could explain commonly reported clinical observations.

Cutaneous wound biofilm and the potential for electrical stimulation in management of the microbiome.

Infection contributes significantly to delayed cutaneous wound healing, which impacts patient care. External application of electrical stimulation (ES) has beneficial effects on wound repair and regeneration. The majority of studies to date have explored ES in relation to planktonic microorganisms, yet evidence indicates that bacteria in chronic wounds reside as antibiotic-resistant polymicrobial biofilms, which contribute to impairing wound healing. Culture-independent sequencing techniques have revolutionized our understanding of the skin microbiome and allowed a more accurate determination of microbial taxa and their relative abundance in wounds allowing a greater understanding of the host-microbial interface. Future studies combining the fields of ES, biofilm and microbiome research are necessary to fully elucidate the use of ES in the management of wound infection.

Effect of Anconeus Muscle Blocking on Elbow Kinematics: Electromyographic, Inertial Sensors and Finite Element Study.

The specific contribution of the anconeus muscle to elbow function is still uncertain. This study aimed to investigate the effect on elbow kinematics and kinetics of blocking anconeus using lidocaine. Ten healthy volunteers performed experimental trials involving flexion-extension and supination-pronation movements in horizontal and sagittal planes. Inertial sensors and surface electromyography were used to record elbow kinematics and kinetics and electrical activity from the anconeus, biceps and triceps brachii before and after blocking anconeus. Moreover, a finite element model of the elbow was created to further investigate the contribution of anconeus to elbow kinematics. The electrical activity results from the trials before blocking clearly indicated that activity of anconeus was increased during extension, suggesting that it behaves as an extensor. However, blocking anconeus had no effect on the elbow kinematics and kinetics, including the angular velocity, net torque and power of the joint. The electrical activity of the biceps and triceps brachii did not alter significantly following anconeus blocking. These results suggest that anconeus is a weak extensor, and the relative small contribution of anconeus to extension before blocking was compensated by triceps brachii. The finite element results indicated that anconeus does not contribute significantly to elbow kinematics.

The efficacy of electrical stimulation in lower extremity cutaneous wound healing: A systematic review.

Current gold standard lower extremity cutaneous wound management is not always effective. Cutaneous wounds generate a "current of injury" which is directly involved in wound healing processes. Application of exogenous electrical stimulation has been hypothesised to imitate the natural electric current that occurs in cutaneous wounds. The aim of this extensive review was to provide a detailed update on the variety of electrical stimulation modalities used in the management of lower extremity wounds. Several different waveforms and delivery methods of electrical stimulation have been used. Pulsed current appears superior to other electrical modalities available. The majority of studies support the beneficial effects of pulsed current over conservative management of lower extremity cutaneous wounds. Although it appears to have no benefit over causal surgical intervention, it is a treatment option which could be utilised in those patients unsuitable for surgery. Other waveforms and modalities appear promising; however, they still lack large trial data to recommend a firm conclusion with regards to their use. Current studies also vary in quantity, quality and protocol across the different modalities. The ideal electrical stimulation device needs to be non-invasive, portable and cost-effective and provides minimal interference with patients' daily life. Further studies are necessary to establish the ideal electrical stimulation modality, parameters, method of delivery and duration of treatment. The development and implementation of newer devices in the management of acute and chronic wounds provides an exciting direction in the field of electrotherapy.

Whole genome microarray data of chronic wound debridement prior to application of dermal skin substitutes.

Clinical consensus is that debridement is necessary for successful application of dermal skin substitutes (DSS) to chronic wounds. The aim here was to identify commonly expressed genes associated with wound healing in untreated acute wounds and chronic wounds treated with wound debridement followed by DSS. Cutaneous biopsies were taken at two time points from untreated acute and chronic wounds and from chronic wounds treated with DSS following debridement. Microarray analysis identified significant differences (p < 0.05) related to proliferation (HIPK2, LGR4, FGFR1, SRRT), migration (RHOC, PRPF40A, FGFR1), differentiation (TCF4, COL13A1, GNPTAB, HUWE1, FGFR1), angiogenesis (HIPK2, CASP8), extracellular matrix organization (VWA1), and apoptosis (BBC3, HIPK2, KLF11, PSME3, MSFD10, TOP2A, MLH1, CASP8, PDIA3, XAF1) when comparing untreated chronic wounds to chronic wounds treated with DSS, with similar expression levels compared to untreated acute wounds. Chronic wounds treated with debridement followed by DSS resemble untreated acute wounds at a genomic level. These novel findings, albeit with limited clinical specimen numbers, strengthen the recommendation to transform chronic into acute wounds prior to application of DSS.

The efficacy of electrical stimulation in experimentally induced cutaneous wounds in animals.

BACKGROUND: Complicated cutaneous wounds and their subsequent management can be a clinical challenge in veterinary medicine. There is still an unmet need for an ideal wound healing therapy that is able to stimulate efficiency and quality of repair. Skin wounds generate large and persistent endogenous electric currents and fields termed the "current of injury". The current of injury is involved in numerous processes of wound healing. These observations have led to the hypothesis that applied electrical stimulation (ES) may promote wound healing by imitating the natural electrical current that occurs in cutaneous wounds. OBJECTIVES: This review details the use, effect and mechanism of ES in different preclinical experimental cutaneous wound models and discusses the potential of how ES could be translated into veterinary practice. RESULTS: Studies have found a variable effect of ES on wound healing. Some have been positive with faster rates of wound re-epithelialization, increased wound collagen formation and angiogenesis noted. Other studies have shown no effect or detrimental results. The effects of ES are highly influenced by the ES modality, polarity and parameters. CONCLUSIONS AND CLINICAL IMPORTANCE: Electrical stimulation has the potential to play a significant role in enhancing cutaneous wound healing in veterinary practice. Clinical studies are necessary to corroborate the findings from experimental studies which have shown promise including the use of alternating pulsed and direct current and the use of bio-electric dressings. The ideal ES device would need to be safe, easy to use, portable, noninvasive and aid wound healing by having a beneficial effect on all wound healing stages.

Optimization of an ex vivo wound healing model in the adult human skin: Functional evaluation using photodynamic therapy.

Limited utility of in vitro tests and animal models of human repair, create a demand for alternative models of cutaneous healing capable of functional testing. The adult human skin Wound Healing Organ Culture (WHOC) provides a useful model, to study repair and enable evaluation of therapies such as the photodynamic therapy (PDT). Thus, the aim here was to identify the optimal WHOC model and to evaluate the role of PDT in repair. Wound geometry, system of support, and growth media, cellular and matrix biomarkers were investigated in WHOC models. Subsequently, cellular activity, extracellular matrix remodeling, and oxidative stress plus gene and protein levels of makers of wound repair measured the effect of PDT on the optimized WHOC. WHOCs embedded in collagen and supplemented DMEM were better organized showing stratified epidermis and compact dermis with developing neo-epidermis. Post-PDT, the advancing reepithelialization tongue was 3.5 folds longer, and was highly proliferative with CK-14 plus p16 increased (p < 0.05) compared to controls. The neo-epidermis was fully differentiated forming neo-collagen. Proliferating nuclear antigen, p16, COLI, COLIII, MMP3, MMP19, and α-SMA were significantly more expressed (p < 0.05) in dermis surrounding the healing wound. In conclusion, an optimal model of WHOC treated with PDT shows increased reepithelialization and extracellular matrix reconstruction and remodeling, supporting evidence toward development of an optimal ex vivo wound healing model.

Skin substitute-assisted repair shows reduced dermal fibrosis in acute human wounds validated simultaneously by histology and optical coherence tomography.

Skin substitutes are heterogeneous biomaterials designed to accelerate wound healing through provision of replacement extracellular matrix. Despite growing evidence for their use in chronic wounds, the role of skin substitutes in acute wound management and their influence on fibrogenesis remains unclear. Skin substitute characteristics including biocompatibility, porosity, and elasticity strongly influence cellular behavior during wound healing. Thus, we hypothesize that structural and biomechanical variation between biomaterials may induce differential scar formation after cutaneous injury. The following human prospective cohort study was designed to investigate this premise. Four 5-mm full thickness punch biopsies were harvested from 50 volunteers. In all cases, site 1 healed by secondary intention, site 2 was treated with collagen-GAG scaffold (CG), and decellularised dermis (DCD) was applied to site 3 while tissue extracted from site 4 was replaced (autograft). Healing tissue was assessed weekly with optical coherence tomography (OCT), before being excised on days 7, 14, 21, or 28 depending on study group allocation for later histological and immunohistochemical evaluation. Extracted RNA was used in microarray analysis and polymerase chain reaction of highlighted genes. Autograft treatment resulted in minimal fibrosis confirmed immunohistochemically and with OCT through significantly lower collagen I levels (p = 0.047 and 0.03) and reduced mean grayscale values (p = 0.038 and 0.015), respectively. DCD developed intermediate scar formation with partial rete ridge reformation and reduced fasiculonodular fibrosis. It was uniquely associated with late up-regulation of matrix metalloproteinases 1 and 3, oncostatin M, and interleukin-10 (p = 0.007, 0.04, 0.019, 0.019). Regenerated dermis was significantly thicker in DCD and autografts 28 days post-injury compared with control and CG samples (p = 0.003 and < 0.0001). In conclusion, variable fibrotic outcomes were observed in skin substitute-treated wounds with reduced scarring in autograft and DCD samples compared with controls. OCT enabled concurrent assessment of wound morphology and quantification of dermal fibrosis.

Ex vivo evaluation of the effect of photodynamic therapy on skin scars and striae distensae.

BACKGROUND: Skin scars and striae distensae (SD) are common dermal disorders with ill-defined treatment options. There is emerging clinical evidence for use of photodynamic therapy (PDT) in treating skin fibrosis. Therefore, the aim here was to investigate the effect of PDT on skin scars and SD in an ex vivo model of human skin scarring. METHODS: Photodynamic therapy, with 5ALA or MALA in addition to illumination with 40 J/cm(2) of red light, was applied to striae alba, fine line, hypertrophic and keloid scars ex vivo (n = 18). General morphology was assessed by H&E, Herovici's and Weigert's differential staining. Apoptosis, proliferation, metalloproteinase 3 and tropoelastin expression were quantified immunohistochemically, and differential gene expression of proliferating cell nuclear antigen (PCNA), collagen (COL) type I and type III, matrix metalloproteinase 3 (MMP3) and tropoelastin (ELN) was assessed by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: Apoptosis increased, which correlated with decreased proliferation and PCNA gene expression. Post-PDT, matrix components were found to be re-organised in both hypertrophic and keloid scars. COLI and COLIII gene expression levels decreased, whilst MMP3 and ELN increased significantly post-PDT compared to normal skin and untreated controls (P < 0.05). However, no significant difference between 5ALA and MALA-PDT treatments was observed. CONCLUSION: Using our unique ex vivo model, we show for the first time morphological and cellular effect of application of PDT, which correlates with the degree and severity of dermal fibrosis. In view of this, PDT may be ideal in targeting treatment of abnormal skin scarring.

Acute cutaneous wounds treated with human decellularised dermis show enhanced angiogenesis during healing.

BACKGROUND: The influence of skin substitutes upon angiogenesis during wound healing is unclear. OBJECTIVES: To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention. METHODS: On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4). In all cases, site 1 healed by secondary intention (control), site 2 was treated with collagen-GAG scaffold (CG), cadaveric decellularised dermis (DCD) was applied to site 3, whilst excised tissue was re-inserted into site 4 (autograft). Depending on study group allocation, healing tissue from sites 1-4 was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used in histological and immunohistochemical evaluation whilst extracted RNA from the remainder enabled whole genome microarrays and qRT-PCR of highlighted angiogenesis-related genes. All wounds were serially imaged over 6 weeks using laser-doppler imaging and spectrophotometric intracutaneous analysis. RESULTS: Inherent structural differences between skin substitutes influenced the distribution and organisation of capillary networks within regenerating dermis. Haemoglobin flux (p = 0.0035), oxyhaemoglobin concentration (p = 0.0005), and vessel number derived from CD31-based immunohistochemistry (p = 0.046) were significantly greater in DCD wounds at later time points. This correlated with time-matched increases in mRNA expression of membrane-type 6 matrix metalloproteinase (MT6-MMP) (p = 0.021) and prokineticin 2 (PROK2) (p = 0.004). CONCLUSION: Corroborating evidence from invasive and non-invasive modalities demonstrated that treatment with DCD resulted in increased angiogenesis after wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and extracellular matrix protease MT6-MMP seen only in the DCD group may contribute to observed responses.