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Patients with cystic fibrosis (CF) experience severe lung disease, including persistent infections, inflammation, and irreversible fibrotic remodeling of the airways. Although therapy with transmembrane conductance regulator (CFTR) protein modulators reached optimal results in terms of CFTR rescue, lung transplant remains the best line of care for patients in an advanced stage of CF. Indeed, chronic inflammation and tissue remodeling still represent stumbling blocks during treatment, and underlying mechanisms are still unclear. Nowadays, animal models are not able to fully replicate clinical features of the human disease and the conventional in vitro models lack a stromal compartment undergoing fibrotic remodeling. To address this gap, we show the development of a 3D full-thickness model of CF with a human bronchial epithelium differentiated on a connective airway tissue. We demonstrated that the epithelial cells not only underwent mucociliary differentiation but also migrated in the connective tissue and formed gland-like structures. The presence of the connective tissue stimulated the pro-inflammatory behaviour of the epithelium, which activated the fibroblasts embedded into their own extracellular matrix (ECM). By varying the composition of the model with CF epithelial cells and a CF or healthy connective tissue, it was possible to replicate different moments of CF disease, as demonstrated by the differences in the transcriptome of the CF epithelium in the different conditions. The possibility to faithfully represent the crosstalk between epithelial and connective in CF through the full thickness model, along with inflammation and stromal activation, makes the model suitable to better understand mechanisms of disease genesis, progression, and response to therapy.

BACKGROUND: The modified Meek technique is not commonly used in equine wound management, despite the consistent reliable and superior results compared with other grafting techniques. Major drawbacks are the need for specialised, expensive equipment and general anaesthesia.
OBJECTIVE: To describe adjustments of the modified Meek technique enabling use in the standing horse without the need for the full equipment. This implied the use of full-thickness skin grafts manually harvested from the pectoral area and manually cut into micrografts. Graft acceptance; healing progress; and final functional and cosmetic result were outcome parameters.
METHODS: Descriptive case series.
METHODS: Eight horses with traumatic wounds at the dorsal side of the carpus or tarsus, healing by second intention, were treated. Original wound areas and areas of graft acceptance and rejection were determined from post-processing of digital photographs and percentage acceptance, wound contraction and epithelialisation were calculated.
RESULTS: The initial mean wound area was 55.4 cm2 . Graft acceptance was 95.3 ± 2.5%. Wound closure was due to 46.0 ± 25.6% wound contraction and 54.0 ± 25.6% epithelialisation and resulted in 96.8 ± 1.9% reduction of the initial wound area 28.0 ± 8.5 days after grafting. The scar was flat, flexible and functional, usually with thin and regular hair growth. The adapted procedure was fast and efficient, with a learning curve for the increased manual work.
CONCLUSIONS: Small study population.
CONCLUSIONS: This adapted modified Meek technique can successfully be performed in the standing horse and obviates the need for the full expensive equipment and general anaesthesia. The acceptance of the full-thickness grafts is excellent resulting in fast and satisfactory healing.

UNASSIGNED: This work reviews the literature regarding spontaneous closure of idiopathic full-thickness macular holes (FTMHs).
UNASSIGNED: Literature on patients with spontaneous idiopathic FTMH closure was reviewed via Ovid MEDLINE, EMBASE, and PubMed through July 16, 2020. A total of 27 of 66 identified articles were included.
UNASSIGNED: A total of 68 eyes had spontaneous closure. Of the patients, 62.7% were women and the average age was 67.5 years. Visual acuity improved from Snellen 20/78 to 20/33 post closure. The average hole diameter was 176.8 μm; the largest was 350 μm. Most were stage 2 according to Gass and of small size according to International Vitreomacular Traction Study Group (IVTS) staging. The predominant classification system in recent literature is IVTS staging. The average optical coherence tomography-observed closure time was 4.5 months.
UNASSIGNED: On review, reported spontaneous closure rates of all idiopathic FTMH range from 3% to 15%, and no demographic subgroups are more likely to have closure. Holes ≤250 µm have higher closure rates (22.2%) than those in the range of >250 to 400 µm (13.3%) and ≥400 µm (0%). Closure is associated with favorable visual outcomes, and retinal bridging via glial cells is likely critical to closure. These determinations were based on limited numbers; prospective studies are needed to further ascertain rate, mechanism, and characteristics. IVTS staging provides reliable reporting and insight into whether FTMH can be observed before surgery.

Large congenital lid colobomas are traditionally repaired using 1- or 2-step vascularized flap-graft combinations. However, visual axis occlusion for weeks is a severe problem in small children and recent reports suggest that the flap pedicle does not contribute to blood perfusion. A \"one-step\" substitute for large lid defects has recently been reported in animals and humans, demonstrating the viability of a bilamellar autograft alone. We present an alternative \"one-step\" reconstructive approach in a 6-month-old infant who had a centrally-located large upper eyelid defect resulting from a congenital coloboma. The free full-thickness bilamellar autograft was harvested from the contralateral upper eyelid. The follow-up time was 48 months. Cosmetic and functional results were good, the bilamellar graft survived, and there was no graft ischemia, necrosis, or rejection. The boy developed madarosis, lid notching, and mild contour irregularity but needed no reoperation since the parent was satisfied with the surgical result. A free bilamellar eyelid autograft seems to be an outstanding alternative to both \"conventional 2-step\" and \"modern 1-step\" options for the reconstruction of large colobomatous eyelid openings, especially in young infants who cannot tolerate visual axis blockage. It is an easy, practical, fast, and effective technique that also saves cost in health care.

In the large full-thickness mouse skin regeneration model, wound-induced hair neogenesis (WIHN) occurs in the wound center. This implies a spatial regulation of hair regeneration. The role of mechanotransduction during tissue regeneration is poorly understood. Here, we created wounds with equal area but different shapes to understand if perturbing mechanical forces change the area and quantity of de novo hair regeneration. Atomic force microscopy of wound stiffness demonstrated a stiffness gradient across the wound with the wound center softer than the margin. Reducing mechanotransduction signals using FAK or myosin II inhibitors significantly increased WIHN and, conversely, enhancing these signals with an actin stabilizer reduced WIHN. Here, α-SMA was downregulated in FAK inhibitor-treated wounds and lowered wound stiffness. Wound center epithelial cells exhibited a spherical morphology relative to wound margin cells. Differential gene expression analysis of FAK inhibitor-treated wound RNAseq data showed that cytoskeleton-, integrin-, and matrix-associated genes were downregulated, while hair follicular neogenesis, cell proliferation, and cell signaling genes were upregulated. Immunohistochemistry staining showed that FAK inhibition increased pSTAT3 nuclear staining in the regenerative wound center, implying enhanced signaling for hair follicular neogenesis. These findings suggest that controlling wound stiffness modulates tissue regeneration encompassing epithelial competence, tissue patterning, and regeneration during wound healing.

BACKGROUND: Full-thickness rotator cuff tears (FTRCTs) represent a common shoulder injury that, if untreated, can progress in size, become increasingly painful, and inhibit function. These lesions are often surgically repaired, with double-row arthroscopic repair often preferred for larger tears. Biological augmentation technologies have been developed to improve rates of postoperative radiographic re-tear and enhance patient-reported outcomes after surgical FTRCT repair. This study sought to confirm that augmented repair with a bioinductive bovine collagen implant results in favorable re-tear rates and patient outcomes with follow-up to 2 years.
METHODS: A prospective multicenter cohort study was undertaken to determine the efficacy and safety of augmenting single- or double-row arthroscopic repair of FTRCTs with a bioinductive bovine collagen implant. Of 115 adult patients participating, 66 (57.4%) had medium (1-3 cm) tears and 49 (42.6%) had large (3-5 cm) tears. Magnetic resonance imaging and patient-reported outcomes (Shoulder and Elbow Surgeons [ASES] Shoulder Score and Constant-Murley Score [CMS]) were performed and recorded at baseline, 3 months, 1 year, and 2 years.
RESULTS: Mean duration of follow-up was 2.1 years (range, 1.5-2.9 years). Between baseline and 2-year follow-up, mean total thickness of the supraspinatus tendon increased by 12.5% for medium tears and by 17.1% for large tears. Radiographic re-tear was noted in 7/61 available patients (11.5%) with medium tears, and in 14/40 patients (35.0%) with large tears. In both groups, these tears primarily occurred before the 3-month follow-up visit (13/21 [61.9%]). Radiographic re-tear with the supplemented double-row (DR) repair technique was 13.2% overall (12/91 DR patients; 11.3% for medium tears and 15.8% for large tears). The minimal clinically important difference (MCID) was achieved by >90% of patients with both medium and large tears for both ASES and CMS. There were 2 serious adverse events classified by the treating surgeon as being possibly related to the device and/or procedure (1 case of swelling/drainage and 1 case of intermittent pain). Nine patients (7.8%; 4 medium tears and 5 large tears) required reoperation of the index rotator cuff surgery.
CONCLUSIONS: Final 2-year data from this study confirm that using this implant in augmentation of arthroscopic double-row repair of FTRCTs provides favorable rates of radiographic re-tear and substantial functional recovery. The relative safety of the device is also further supported.

There is a global trend towards the development of physiologically relevant in vitro skin models to reduce or replace animal testing in the evaluation of therapeutic drug candidates. However, only commercial reconstructed human epidermis models (RHEm) have undergone formal validation. Although these commercial models are suitable for a wide range of applications, they are costly, lack flexibility, and the protocols used to generate them are not transparent. In this study, we present an open-source full-thickness skin model (FTSm) and assess its potential for drug testing. The FTSm was developed using endogenous extracellular matrix to recreate the dermal compartment, avoiding animal-derived hydrogels. An RHEm based on an open-source protocol was evaluated in parallel. The integrity of the skin barrier was analyzed by challenging the surface with detergents and measuring cell viability as well as by trans-epithelial electrical resistance (TEER) measurements. Skin irritation studies were performed based on OECD guidelines and complemented with an evaluation of the impact on the skin barrier by TEER measurement. The permeation of a dye through the developed models and a commercial membrane (Strat-M®) was compared using Franz diffusion cells and an infinite dose approach. The FTSm demonstrated structural and barrier properties comparable to native human skin. Although the RHEm showed a better performance in drug testing, the FTSm presented better barrier properties than commercial models as reported in the literature. These skin models can be a valuable contribution to accelerating the development and dissemination of alternatives to animal testing, avoiding the limitations of commercial models.

Historically, nose piercing was considered as the symbol of elegance and sometimes also associated with regional ritual. In modern civilization, there has been a decreasing trend to wear nose rings and some people demand for its closure. Herein, we report a case series of three patients who were successfully managed with full-thickness skin grafting for the closure of nose piercing site.

BACKGROUND: To evaluate the use of allogenic freeze-dry PRP for the full-thickness wound healing process in experimental animals (rabbits).
METHODS: This study is an experimental research using the posttest-only design, a simple randomized design. Thirty rabbits were randomly divided into six groups (three control groups and three treatment groups), and each group consisted of five subjects. Skin-thick cuts were made on the back of each rabbit. Wounds in the control group were treated using a paraffin gauze, and allogenic freeze-dried PRP was given to the treatment group; observations were made on the 3rd, 9th, and 14th days. The t-test on two random samples and Mann-Whitney were used to process data. The results were significant at p < 0.05.
RESULTS: There were significant differences in the average number of fibroblasts the control groups and the treatment groups on day 3 (p = 0.009), day 9 (p = 0.023), and day 14 (p < 0.001). There were also major differences in the average amount of neovascularization between the control group and the treatment group on day 3 (p = 0.034), day 9 (p < 0.001), and day 14 (p < 0.001).
CONCLUSIONS: The application of allogenic freeze-dried PRP was confirmed to be able to increase the number of fibroblasts and neovascularization in the full-thickness wound healing process in rabbits.