Fibroblast Activation Protein Targeted Photodynamic Therapy Selectively Kills Activated Skin Fibroblasts from Systemic Sclerosis Patients and Prevents Tissue Contraction

Systemic sclerosis (SSc) is a rare, severe, auto-immune disease characterized by inflammation, vasculopathy and fibrosis. Activated (myo)fibroblasts are crucial drivers of this fibrosis. By exploiting their expression of fibroblast activation protein (FAP) to perform targeted photodynamic therapy (tPDT), we can locoregionally deplete these pathogenic cells. In this study, we explored the use of FAP-tPDT in primary skin fibroblasts from SSc patients, both in 2D and 3D cultures. Method: The FAP targeting antibody 28H1 was conjugated with the photosensitizer IRDye700DX. Primary skin fibroblasts were obtained from lesional skin biopsies of SSc patients via spontaneous outgrowth and subsequently cultured on plastic or collagen type I. For 2D FAP-tPDT, cells were incubated in buffer with or without the antibody-photosensitizer construct, washed after 4 h and exposed to λ = 689 nm light. Cell viability was measured using CellTiter Glo®®. For 3D FAP-tPDT, cells were seeded in collagen plugs and underwent the same treatment procedure. Contraction of the plugs was followed over time to determine myofibroblast activity. Results: FAP-tPDT resulted in antibody-dose dependent cytotoxicity in primary skin fibroblasts upon light exposure. Cells not exposed to light or incubated with an irrelevant antibody-photosensitizer construct did not show this response. FAP-tPDT fully prevented contraction of collagen plugs seeded with primary SSc fibroblasts. Even incubation with a very low dose of antibody (0.4 nM) inhibited contraction in 2 out of 3 donors. Conclusions: Here we have shown, for the first time, the potential of FAP-tPDT for the treatment of fibrosis in SSc skin.

Nitric oxide could promote development of Barrett's esophagus by S-nitrosylation-induced inhibition of Rho-ROCK signaling in esophageal fibroblasts

Barrett's esophagus arises in the process of wound healing in distal esophageal epithelium damaged by gastroesophageal reflux disease. Differentiation of fibroblast into myofibroblasts, a smooth muscle cell-like phenotype and tissue contraction are crucial processes in wound healing. No study has evaluated mechanism by which luminal esophageal nitric oxide (NO) affect Rho-associated coiled-coil forming protein kinase (Rho-ROCK) signaling pathway, a key factor of tissue contraction, in stromal fibroblasts to develop Barrett's esophagus. Using esophageal fibroblasts, we performed collagen-based cell contraction assays and evaluated influence of Rho-ROCK signaling in the exposure to acidic bile salts and NOC-9, which is an NO donor. We found that enhanced cell contraction induced by acidic bile salts was inhibited by NO, accompanied by decrease in phosphorylated myosin light chain expression and stress fiber formation. NO directly S-nitrosylated GTP-RhoA and consequently blocked Rho-ROCK signaling. Moreover, exposure to NO and Y27632, a Rho-ROCK signaling inhibitor, decreased a-SMA expression and increased bone morphogenetic protein 4 (BMP4) expression and secretion. These findings could account for the increased expression of BMP4 in the columnar epithelial cells and stromal fibroblasts in human Barrett's esophagus. NO could impair wound healing by blocking the Rho-ROCK signaling pathway and promote development of Barrett's esophagus.

Applications of Helium Plasma in Rejuvenation of the Face and Neck

Energy based devices have been developed for the purposes of tissue contraction and skin tightening. Its application in the face and neck have been explored using lasers, temperature controlled monopolar and bipolar radiofrequency, and ultrasound. The purpose of this chapter is to explore the various applications for the face and neck using Renuvion™, a unique energy driven device based on plasma generated from the combination of helium gas and radiofrequency energy. The advantage of this technology is its ability to offer precise delivery of heat to tissue with minimal thermal spread, in part due to the rapid cooling aided by the helium gas. We will explore the options in which this technology can be incorporated to rejuvenate the face and neck, the patient selection considerations in choosing method of approach, surgical technique, anticipated outcomes, potential concerns and or complications associated with this and expected perioperative care. Applications in the face and neck include: (1) Subdermally in the neck as a stand alone procedure with or without liposuction. (2) Subdermally in a limited incision, non-excisional technique with a concomitant platysmaplasty either with an open approach or percutaneous use of suture suspension for the platysmal muscle. (3) Subdermally in conjunction with an open traditional rhytidectomy involving skin excision. (4) Ablative resurfacing—fractional or pulsed and full continuous modalities (non-FDA cleared at the time of this writing). It is the authors’ experience that with appropriate patient selection this can be a powerful tool that can deliver skin tightening and rhytid reduction not seen by other technologies available.

Enhanced Abdominal Contouring

This chapter will discuss the various energy-based modalities that are available to optimize circumferential trunk liposuction to enhance patient results. We will discuss multimodal liposuction using power assisted liposuction, ultrasonic energy addition, as well as radiofrequency assisted modalities to achieve adipose reduction and concurrent skin and soft tissue contraction. An in-depth look at patient selection and intraoperative technique will be presented. The postoperative management for each modality will be discussed in detail, including expected results from each modality and potential complications and their ensuing management. We will also discuss the application of different modalities alone and in combination to achieve superior results.

Multiphysics modelling of photon, mass and heat transfer in coral microenvironments

Coral reefs are constructed by calcifying coral animals that engage in a symbiosis with dinoflagellate microalgae harboured in their tissue. The symbiosis takes place in the presence of steep and dynamic gradients of light, temperature and chemical species that are affected by the structural and optical properties of the coral and their interaction with incident irradiance and water flow. Microenvironmental analyses have enabled quantification of such gradients and bulk coral tissue and skeleton optical properties, but the multi-layered nature of corals and its implications for the optical, thermal and chemical microenvironment remains to be studied in more detail. Here, we present a multiphysics modelling approach, where three-dimensional Monte Carlo simulations of the light field in a simple coral slab morphology with multiple tissue layers were used as input for modelling the heat dissipation and photosynthetic oxygen production driven by photon absorption. By coupling photon, heat and mass transfer, the model predicts light, temperature and O 2 gradients in the coral tissue and skeleton, under environmental conditions simulating, for example, tissue contraction/expansion, symbiont loss via coral bleaching or different distributions of coral host pigments. The model reveals basic structure–function mechanisms that shape the microenvironment and ecophysiology of the coral symbiosis in response to environmental change.

Furnishing Wound Repair by the Subcutaneous Fascia

Mammals rapidly heal wounds through fibrous connective tissue build up and tissue contraction. Recent findings from mouse attribute wound healing to physical mobilization of a fibroelastic connective tissue layer that resides beneath the skin, termed subcutaneous fascia or superficial fascia, into sites of injury. Fascial mobilization assembles diverse cell types and matrix components needed for rapid wound repair. These observations suggest that the factors directly affecting fascial mobility are responsible for chronic skin wounds and excessive skin scarring. In this review, we discuss the link between the fascia’s unique tissue anatomy, composition, biomechanical, and rheologic properties to its ability to mobilize its tissue assemblage. Fascia is thus at the forefront of tissue pathology and a better understanding of how it is mobilized may crystallize our view of wound healing alterations during aging, diabetes, and fibrous disease and create novel therapeutic strategies for wound repair.

Evaluation of a novel bioactive wound dressing: an in vitro and in vivo study

Objective: Hard-to-heal wounds, such as pressure ulcers and diabetic ulcers, are a major challenge for wound dressings. The aim of this study was to develop a bioactive dressing based on polymers and natural materials with unique biological and therapeutic properties. Method: The dressing was composed of an active layer containing polyvinyl alcohol (PVA), honey, curcumin and keratin, and an upper layer with lower hydrophilicity comprising PVA to induce flexibility. Physicochemical properties of the dressing were characterised by Fourier transform infrared spectroscopy, field emission scanning electron microscopy, swelling behaviour and antibacterial measurements. A wound healing study was performed using an experimental rat model and two different compositions of the bioactive dressing were compared with a commercial wound dressing (Comfeel, Coloplast, Denmark). Histopathological evaluation was conducted for this purpose. Results: Characterisation results showed that a smooth bilayer film with two homogenous but distinct layers was produced. The dressing also provided adequate moisture to the wound environment without infection and adhesion due to dryness occurring. Our results exhibited significant bactericidal activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and improved the wound healing process without any scarring. Histopathological findings demonstrated a significant higher healing rate in vivo together with well-formed epidermis, granulation tissue formation and tissue contraction, when compared with the commercial wound dressing. Conclusion: Our results demonstrated acceptable physical and healing effects for the novel bioactive wound dressing; however, more investigations are recommended.

Internal and External Radiofrequency Assisted Lipo-Coagulation (RFAL) in the Control of Soft Tissue Contraction during Liposuction: Part 1 “Inside Out” Thermal Tissue Tightening

Radiofrequency Assisted Lipo-coagulation (RFAL) BodyTite is a contact, impedance, internal and external thermal regulation controlled, internal, minimally invasive, non-excisional procedure providing soft tissue lipo-coagulation and contraction that has been used for over 10 years to optimize skin and soft tissue contraction during liposuction procedures. The device deploys a bipolar applicator inserted into the liposuction zone. The internal, coated, electrode is positively charged and emits a coagulative, ablative injury that results in adipose liquification and Fibroseptal Network (FSN) contraction. The RF flows from the internal electrode after ablation and coagulation up to the external negatively charged return electrode moving on the skin, which heats and tightens the papillary dermis non-ablatively. The body areas that most benefit from this BodyTite technology and procedure include those areas most in need of non-excision contraction include the abdomen, upper arms, inner thighs, bra-line, neck and jaw line. Studies, show, that the combination of BodyTite internal thermal coagulation and external Morpheus8 (see Part 2) at the time of liposuction can result in 40–70% area skin contraction, greatly improving the soft tissue contours and Body shaping outcomes following lipo-contouring procedures.

Comparison of Surgical Complications Rates Between LigaSure Small Jaw and Clamp-and-Tie Hemostatic Technique in 1,000 Neuro-Monitored Thyroidectomies

Over the past decade, the use of neuromonitoring in thyroid surgery has become well established and is increasing accepted across the world. In addition, new developments in energy devices have significantly improved efficacy in achieving hemostasis in thyroid surgery. Few studies focused on the complication rates in energy device-assisted sutureless neuro-monitored thyroidectomy. This study investigates a novel LigaSure Small Jaw (LSJ) technique for sutureless thyroidectomy and compares the surgical complication rates between LSJ and conventional clamp-and-tie technique in one thousand consecutive neuro-monitored thyroidectomy patients. Five hundred patients received sutureless thyroidectomy performed with LSJ (Group L), and 500 patients received surgery performed with conventional clamp-and-tie technique (Group C). Complication rates of postoperative hematoma, hypocalcemia and recurrent laryngeal nerve (RLN) palsy were compared between groups. The overall complication rates of hematoma, hypocalcemia (temporary/ permanent), and RLN (temporary/ permanent) palsy were 0.9%, 24.9% (24.6%/0.3%), and 1.7% (1.5%/0.2%), respectively. Group L and Group C significantly differed in postoperative hematoma rate (0.0% vs. 1.8%, respectively; p = 0.0026) and in postoperative hypocalcemia rate (20.1% vs. 30.0%, respectively; p = 0.0032). The incidence of RLN palsy did not significantly differ between Group L and Group C (1.38% vs. 2.08%; p = 0.2652). The overall surgical complication rates are low in neuro-monitored thyroidectomy. The LSJ is feasible for performing completely sutureless thyroidectomy and obtains superior outcomes of postoperative hematoma and hypocalcemia in comparison with clamp-and-tie hemostatic technique. The novel LSJ technique using double or overlapped sealing is useful for sutureless thyroidectomy. However, surgeons must carefully observe the tissue contraction that may reduce the LSJ-RLN distance and increase the risk of thermal injury during the LSJ activation.