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Cellular therapies hold promise to replace the implantation of whole organs in the treatment of disease. For most cell types, in vivo viability depends on oxygen delivery to avoid the toxic effects of hypoxia. A promising approach is the in situ vascularization of implantable devices which can mediate hypoxia and improve both the lifetime and utility of implanted cells and tissues. Although mathematical models and bulk measurements of oxygenation in surrounding tissue have been used to estimate oxygenation within devices, such estimates are insufficient in determining if supplied oxygen is sufficient for the entire thickness of the implanted cells and tissues. We have developed a technique in which oxygen-sensitive microparticles (OSMs) are incorporated into the volume of subcutaneously implantable devices. Oxygen partial pressure within these devices can be measured directly in vivo by an optical probe placed on the skin surface. As validation, OSMs have been incorporated into alginate beads, commonly used as immunoisolation devices to encapsulate pancreatic islet cells. Alginate beads were implanted into the subcutaneous space of Sprague–Dawley rats. Oxygen transport through beads was characterized from dynamic OSM signals in response to changes in inhaled oxygen. Changes in oxygen dynamics over days demonstrate the utility of our technology.

IMPORTANCE The use of costal cartilage as a graft in facial reconstructive surgery requires sectioning the cartilage into a suitable shape. OBJECTIVE To evaluate the accuracy of a novel mechanical device for producing uniform slices of costal cartilage and to illustrate the use of the device during nasal surgery. DESIGN Basic and clinical study using 100 porcine ex vivo costal cartilage slices and 9 operative cases. METHODS This instrument departs from antecedent devices in that it uses compression to secure and stabilize the specimen during sectioning. A total of 75 porcine costal cartilage ribs were clamped with minimal compression just sufficient to secure and stabilize the specimen while cutting. Slices having a length of 4 cm and width of 1 cm were obtained using the cartilage cutter at 3 thicknesses: 1 mm (n = 25), 2 mm (n = 25), and 3 mm (n = 25). The procedure was repeated for the 2-mm thick samples; however, the ribs in this group (n = 25) were clamped using the maximum amount of compression attainable by the device. Thickness was measured using a digital micrometer. Case presentations illustrate the use of the device in secondary and reconstructive rhinoplasty surgery. RESULTS All specimens were highly uniform in thickness on visual inspection and appeared to be adequate for clinical application. Sectioning was completed in several seconds without complication. In the porcine specimens sectioned using minimal compression, the percentage difference in thickness for each individual sample averaged 18%, 10%, and 11% for the 1-mm-, 2-mm-, and 3-mm-thick slices, respectively. Within the specimens sectioned using maximum compression, the percentage difference in thickness for each individual sample averaged 35% for the 2-mm-thick slices. In the setting of nasal reconstructive surgery, slices having a thickness from 1 to 2 mm were found to be well suited for all necessary graft types. CONCLUSIONS AND RELEVANCE The simple mechanical device described produces costal cartilage graft slices with highly uniform thickness. Securing the rib by clamping during cutting reduces uniformity of the slices; however, the imperfections are minimal, and all sectioned grafts are adequate for clinical application. The device can be adjusted to produce slices of appropriate thickness for all nasal cartilage grafts. This device is valuable for reconstructive procedures owing to its ease of use, rapid operation, and reproducible results.

IMPORTANCE The use of costal cartilage as a graft in facial reconstructive surgery requires sectioning the cartilage into a suitable shape. OBJECTIVE To evaluate the accuracy of a novel mechanical device for producing uniform slices of costal cartilage and to illustrate the use of the device during nasal surgery. DESIGN Basic and clinical study using 100 porcine ex vivo costal cartilage slices and 9 operative cases. METHODS This instrument departs from antecedent devices in that it uses compression to secure and stabilize the specimen during sectioning. A total of 75 porcine costal cartilage ribs were clamped with minimal compression just sufficient to secure and stabilize the specimen while cutting. Slices having a length of 4 cm and width of 1 cm were obtained using the cartilage cutter at 3 thicknesses: 1 mm (n = 25), 2 mm (n = 25), and 3 mm (n = 25). The procedure was repeated for the 2-mm thick samples; however, the ribs in this group (n = 25) were clamped using the maximum amount of compression attainable by the device. Thickness was measured using a digital micrometer. Case presentations illustrate the use of the device in secondary and reconstructive rhinoplasty surgery. RESULTS All specimens were highly uniform in thickness on visual inspection and appeared to be adequate for clinical application. Sectioning was completed in several seconds without complication. In the porcine specimens sectioned using minimal compression, the percentage difference in thickness for each individual sample averaged 18%, 10%, and 11% for the 1-mm-, 2-mm-, and 3-mm-thick slices, respectively. Within the specimens sectioned using maximum compression, the percentage difference in thickness for each individual sample averaged 35% for the 2-mm-thick slices. In the setting of nasal reconstructive surgery, slices having a thickness from 1 to 2 mm were found to be well suited for all necessary graft types. CONCLUSIONS AND RELEVANCE The simple mechanical device described produces costal cartilage graft slices with highly uniform thickness. Securing the rib by clamping during cutting reduces uniformity of the slices; however, the imperfections are minimal, and all sectioned grafts are adequate for clinical application. The device can be adjusted to produce slices of appropriate thickness for all nasal cartilage grafts. This device is valuable for reconstructive procedures owing to its ease of use, rapid operation, and reproducible results.

Melanoma is a lethal form of skin cancer with poor prognosis, especially due to the early metastatic feature. Recent studies have shown that the melanin pigment influences the nanomechanical properties and, therefore, the metastatic behavior of the melanoma cells. We aimed to study the growth of subcutaneously transplanted syngeneic melanoma tissue in female C57BL/6 mice harvested from a mouse with a four-week B16F10 melanoma. Also, we studied the effect of the melanin pigment loading on the peritumoral migratory abilities of melanoma cells. Even when the syngeneic transplant was different (cultured cells vs. tumor tissue), the morphological features and the tumor growth were similar in both groups of mice. Heavily pigmented melanoma cells had low migration abilities. Angiogenesis, the depigmentation phenomenon, and the cell shape changes were related to pigmented melanoma cell migration along the matrix collagen fibers of peritumoral structures: the abluminal face of the vessels (angiotropism), the endomysium, and the nerves (neurotropism). The replacement of the histopathological growth pattern, the absence of angiogenesis, and rapidly tumor-bearing emboli were correlated with amelanotic and low pigmented melanoma cells. This study demonstrated that syngeneic melanoma tissue transplantation was a viable technique, and that the melanin pigment loading level can affect the melanoma cell migration profile.

The safety of the tissue transplant recipient is a top priority for tissue banks, and the emergence of the new coronavirus SARS-CoV-2 has raised significant concerns about the risks of releasing tissue for clinical use. In the present study, we conducted a literature review about the potential infectivity of SARS-CoV-2 in different biological tissues and the influence of various tissue processing and sterilization procedures on viral inactivation. The search revealed that SARS-CoV-2 binds to the human angiotensin-converting enzyme receptor to penetrate human cells. These receptors are present in skin cells, musculoskeletal tissue, amniotic membranes, cardiovascular tissue and ocular tissues, including the cornea. In general, we found that coronaviruses are stable at low temperatures, and inactivated upon exposure to extreme heat and pH. Notably, gamma irradiation, which has already been employed to inactivate SARS and MERS, could be useful for sterilizing skin, amnion and musculoskeletal tissues against SARS-CoV-2. We conclude that due to the limited information about the effects of physical and chemical tissue processing methods on viral neutralization, rigorous donor screening is still essential for tissue transplant recipient safety. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the management methods of female urethral stricture (FUS) and analyze the outcomes of surgical treatments. A meta‐analysis was done in an attempt to identify the best approach of urethroplasty and the graft‐of‐choice. Materials and Methods: A systematic search of Pubmed/Medline and Embase databases was performed according to the Preferred Reporting Items For Systematic Review And Meta‐Analysis statement, for articles reporting on FUS management in the last decade. The Newcastle‐Ottawa scale was used to assess the quality of 28 included non‐randomized studies. The data on FUS management was summarized and pooled success rates (taken as symptom improvement and no need for further instrumentation) were compared. The secondary outcome was to establish a diagnostic modality of choice and define a "successful‐outcome" of repair. Results: The outcome was separately reported for 554 women undergoing surgical intervention for FUS in the literature. The criteria defining FUS were varied. A combination of tests was used for diagnosis as none was singularly conclusive. A total of 301 patients had previous urethral instrumentations. The pooled success rate of urethral dilatation (234 women) was 49% at a mean follow‐up of 32 months; flap urethroplasty (108 cases) was 92% at a mean follow‐up of 42 months; buccal mucosal graft (BMG) urethroplasty (133 cases) was 89% at a mean follow‐up of 19 months; vaginal graft augmentation (44 cases) was 87% at a mean follow‐up of 15 months; and labial graft reconstruction (19 cases) was 89% at a mean follow‐up of 18.4 months. The dorsal approach of graft augmentation met with 88% (95% confidence interval [CI] 0.79–0.95) success compared with 95% (95% CI 0.86–1) for the ventral approach. Conclusion: FUS is a rare condition requiring a meticulous diagnostic workup using multiple tests. All urethroplasties have shown better pooled success rates (86%–93%) compared with dilatation (49%). BMG is equally effective as vaginal graft urethroplasty. [ABSTRACT FROM AUTHOR]

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Objectives: This study aimed to evaluate the mucograft collagen matrix (CM) to increase keratinized tissue around teeth compared to free gingival graft (FGG). Materials and Methods: The present double-blind, randomized, controlled clinical trial studied 12 patients who had 2 mm or less keratinized gingiva bilaterally around mandibular premolars. The 6-month width of keratinized tissue, periodontal parameters (preoperatively and 1, 3, and 6 months postoperatively), color match, pain, and total surgical time were measured. Results: The mean dimensional change of keratinized gingiva 6 months postoperatively was 4.1±0.7 mm for FGG and 8±1.7 mm for CM. Periodontal parameters were not affected in the two groups. The CM group had a significantly lower pain, experienced less surgery time, and gained better aesthetics compared to the FGG group. Conclusion: CM appears to be a suitable substitute for FGG in procedures designed to increase keratinized tissue around teeth. It has remarkable benefits, such as acceptable keratinized tissue gain, less pain, less surgical chair time, and better aesthetics.

This article focuses on the emerging field of equine regenerative medicine with an emphasis on the use of mesenchymal stem cells (MSCs) for orthopedic diseases. We detail laboratory procedures and protocols for tissue handling and MSC isolation, characterization, expansion, and cryopreservation from bone marrow, fat, and placental tissues. We provide an overview of current clinical uses for equine MSCs and how MSCs function to heal tissues. Current laboratory practices in equine regenerative medicine mirror those in the human field. However, the translational use of autologous and allogeneic MSCs for patient therapy far exceeds what is currently permitted in human medicine.

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.

Large and ptotic breast reconstruction in patients who are not candidates for a transverse rectus abdominalis myocutaneous flap and revision surgery for the contralateral breast remains challenging. We developed a novel breast reconstruction technique using a latissimus dorsi myocutaneous (LD m-c) flap set at the posterior aspect of the reconstructed breast, combined with an anatomical silicone breast implant (SBI), following tissue expander surgery. We performed the proposed technique in four patients, in whom the weight of the resected tissue during mastectomy was >500 g and the depth of the inframammary fold (IMF) was >3 cm. After over-expansion of the lower portion of the skin envelope by a tissue expander, the LD m-c flap was transferred to cover the lower portion of the breast defect and to achieve a ptotic contour, with the skin paddle set at the posterior aspect of the reconstructed breast. An SBI was then placed in the rest of the breast defect after setting the LD m-c flap. No major complications were observed during the follow-up period. The proposed technique resulted in symmetrical and aesthetically satisfactory breasts with deep IMFs, which allowed proper fitting of the brassiere, following large and ptotic breast reconstruction.

Cell replacement therapy is one of the top priority areas of modern medicine, which is aimed at restoring the structure and functions of damaged tissues by transplanting cells grown in vitro . The article summarizes data obtained in several studies of diploid cell lines (allogeneic fibroblasts) used as replacement therapy in various therapeutic areas as part of application of medical technology innovations. The article describes benefits of using fibroblasts and the routes of cell culture administration. At present the use of medicinal products containing viable human cells (biomedical cell products) is regulated by Federal Law 180-FZ «On biomedical cell products» of 23 June 2016. Cell cultures used in the production of biomedical cell products should be morphologically homogeneous populations of cells derived from a specific tissue and should have a limited life span, a stable karyotype (at least 75 % of cells should have a double set of chromosomes), should not be associated with cancer risks, be free from extraneous agents, have low levels of histocompatibility antigens expression. According to 180-FZ, all characteristics of a cell line supporting the quality of a biomedical cell product should be reflected in the biomedical cell product specification. Before the adoption of 180-FZ only certified cell cultures could be clinically used. The therapeutic potential of fibroblasts related to optimization of reparative processes, improvement of regenerative and adaptive capabilities, as well as the accumulated experience of their clinical use are stirring interest to the development of fibroblast-based biomedical cell products and their use as replacement therapy. However, it should be pointed out that according to 180-FZ biomedical cell products may not be produced using «biological material obtained by interrupting or jeopardising an embryo/fetus development process».

Human organ and tissue transplantation was started in India in 1962. Initially, the organ transplant was unregulated, and organ trafficking was rampant. The act governing the transplantation was passed in 1994. This has been subsequently amended in 2011, and new rules came into force in 2014. Many of the students as well as practicing physicians are not aware of the act as it is generally not a part of the curriculum. This article highlights the important components of the act and focuses on what all physicians involved in transplant should know about the legal aspects of transplantation.

Introduction: Historically, the treatment of palatal recession was thought to be extremely challenging if not impossible due to the anatomy of the palate. A novel technique is presented for treating gingival recession on maxillary molars utilizing a rotated subepithelial connective tissue pedicle graft. The technique is designed to maximize perfusion to the graft as compared to a free graft Case Presentations: The authors present two cases in which the technique was utilized to achieve attachment gain and root coverage. The cases were followed for at least 2 months. Conclusions: More than 5 mm of attachment was gained and 55% to 60% root coverage achieved over recession defects on maxillary first molars. The following case reports demonstrate that the Reverse Palatal Pedicle Graft (RPPG) technique was successful in improving root coverage over maxillary palatal recession defects. [ABSTRACT FROM AUTHOR]

Summary: We herein investigate the safety and efficacy of single‐agent anti‐rejection regimens in a mouse vascularized composite allotransplantation (VCA) model. Orthotopic hind‐limb transplantations (Balb/c → C57BL/6) were performed using 6‐ to 8‐week‐old mice. A thirty‐day regimen of either rapamycin, tacrolimus (both 1, 3, 5 mg/kg/day) or cyclosporine (25, 35, 50 mg/kg/day) was used. Primary endpoints were animal and graft survival, and secondary chimerism and regulatory T‐cell levels. For rapamycin and tacrolimus given at 1, 3, and 5 mg/kg/day, median graft survival time (MST) was 23 days (18–28 days), 30 days (23–30 days), and 30 d (30–30 days) and 14 days (13–18 days), 30 days (16–30 days), and 30 days (30–30 days), respectively. For cyclosporine dosed at 25 and 35 mg/kg/day, MST was 15 days (12–18 days) and 21 days (14–27 days). Toxicity from CsA 50 mg/kg led to 100% mortality. Mixed chimerism levels were higher in rapamycin‐treated animals than in tacrolimus‐treated recipients (P = 0.029). Tacrolimus was superior in preventing leukocyte recruitment to the allograft. In murine VCA, no standardized immunosuppressive regimen exists, limiting comparability of outcomes and survival. Our data demonstrate that rapamycin and tacrolimus maintenance treatment at 5 mg/kg/day both yielded allograft survival (

Tissue donation is important to reverse cornea‐related blindness. Unfortunately, the willingness to make a decision concerning organ and tissue donation while still alive remains low despite all efforts. By analyzing anonymized archived data from 25 654 next‐of‐kin interviews from our database over a period of 5 years (2013‐2018), it was found that only 20.8% of all potential cornea donors have declared their own wishes. While still alive, refusal was communicated more often than consent by potential donors. Overall consent rates were 39.2%, with parents and siblings consenting more often than other relatives and females refusing more often than male family members. Personal interviews and interviews via telephone handled by staff known to the family resulted in better consent rates (up to 75.6%) with male interviewers receiving higher consent rates in general. The gender of the approached relatives in relation to a male/female interviewer was of low importance. The results also show that it is important to allow discussion about that topic between family members—the more relatives that were involved the higher the probability of consent. [ABSTRACT FROM AUTHOR]

The loss of fertility and early menopause are common after gonadotoxic therapies and radical pelvic surgery. The strategy of ovarian tissue cryopreservation and auto-transplantation was introduced to prevent this significant quality of health issue. Ovarian transplantation with cryopreserved tissue has gone through remarkable evolution in the last 20 years. In this review, we detail the history and evolution of ovarian transplantation with cryopreserved tissue from its origins to the present. Ovarian cryopreservation and transplantation approach was first tested with animal models. The approach was then validated in human ovarian xenografting models before being applied to patients in pioneering clinical studies. The first orthotopic and heterotopic approaches to ovarian transplantation was developed by Oktay et al. who reported the first successful restoration of ovarian function with these approaches beginning in 2000 with first embryo development in 2004. Controversy remains on when the first live birth occurred after orthotopic ovarian transplantation with cryopreserved tissue as the patient was ovulating with elevated progesterone levels in the case reported in 2004; first live birth is likely to be the one reported by Meirow et al. in 2005. Nevertheless, the technique has evolved to reach a level where most recent live birth rates are exceeding 35% and the procedure is no longer considered experimental by many. [ABSTRACT FROM AUTHOR]

Precise, expensive individual saw guides are used with increasing frequency for the reconstruction of mandibular defects with fibular grafts. In this report, an alternative is presented – the Multiuse Cutting Jig (MUC-Jig, proprietary development). It is reusable, suitable for all patients, requires simple planning based on conventional CT imaging, and is more economical. To investigate its precision, we conducted a nonblinded experimental study, with ten participating craniomaxillofacial surgeons. Osteotomies of four different fibula segments were carried out at the same angulation, with groups defined according to the proximal and distal fixed angulation: 45°, 30°, 15°, or 0°. The sagittal cut was performed proximally, with the coronal cut performed distally. The resulting 40 segments (n = 40) were analyzed with their Tx length (primary endpoint) and osteotomy angles, and compared to the original planning. The mean (SD) relative deviation of all grafts from the original planning was –0.08 mm (1.12) in length and –0.71° (3.15) for the angle. Only 45° (–2.04 ± 3.71°) and 30° (–1.07 ± 2.52°) cuts differed significantly (p < 0.05) from smaller angle grafts. The mean (SD) absolute deviation was 0.81 mm (0.27) in length and 2.13° (0.93) in graft angles. For individual transplants, 45° cuts (1.28 ± 1.03 mm) differed significantly (p < 0.005) from others. We observed no differences in relative length or absolute angle deviation. The MUC-Jig is precise and cost-effective for osteotomies with medium angles and smooth reconstructions of template-guided procedures. [ABSTRACT FROM AUTHOR]

Background: For replacement of the lost tissue due to trauma and burns, several methods were used; tissue expander in one of them, but few studies has been done about it. This study aimed to compare vascular density in the expanded tissue versus normal tissue in patients with missing tissue. Methods: In a clinical trial study in 2015-2016, 25 candidates for tissue expander were enrolled. Subcutaneous tissue expander was placed and after completion of treatment, at the time getting expanders out of the body, 5 samples were given from expanded capsule, subcutaneous of expanded tissue, subcutaneous of not-expanded tissue, expanded skin, and not-expanded skin. Vascular density of the samples were determined by a pathologist and were compared with healthy tissue of adjacent area. Findings: The mean vascular density in expanded capsule, subcutaneous of expanded tissue, and subcutaneous of not-expanded tissue were 8.96 ± 4.73, 7.36 ± 3.29, and 5.08 ± 2.40 per mm2, respectively; vascular density of subcutaneous of expanded and not-expanded tissue was statistically different (P < 0.001). Conclusion: Using expanded tissue for destroyed tissue replacement is an efficient method in patients who need it; developing tissue with this method leads to development of vascularity in expanded tissue.

The soft tissue triangle is an easily recognizable subunit of the nose. Therefore, deformities in this region resulting from trauma or complications after cosmetic surgery can have serious cosmetic impacts. Various reconstruction choices exist for deformities such as depression of the soft triangle but choosing the most appropriate treatment in each case remains a challenge. In the case described herein, a patient underwent augmentation rhinoplasty with a silastic implant and experienced implant exposure in the soft triangle area. After implant removal, the patient complained of depression in this area. The authors effectively solved this problem through a de-epithelialized composite tissue graft. In this report, we present this case and review similar cases of reconstruction of the soft triangle. [ABSTRACT FROM AUTHOR]

In the United States, there is currently no system to track donated human tissue products to individual recipients. This posed a challenge during an investigation of a nationwide tuberculosis outbreak that occurred when bone allograft contaminated with Mycobacterium tuberculosis (Lot A) was implanted into 113 patients in 18 US states, including 2 patients at 1 health care facility in Colorado. A third patient at the same facility developed spinal tuberculosis with an isolate genetically identical to the Lot A outbreak strain. However, health care records indicated this patient had received bone allograft from a different donor (Lot B). We investigated the source of this newly identified infection, including the possibilities of Lot B donor infection, product switch or contamination during manufacturing, product switch at the health care facility, person-to-person transmission, and laboratory error. The findings included gaps in tissue traceability at the health care facility, creating the possibility for a product switch at the point of care despite detailed tissue-tracking policies. Nationally, 6 (3.9%) of 155 Lot B units could not be traced to final disposition. This investigation highlights the critical need to improve tissue-tracking systems to ensure unbroken traceability, facilitating investigations of recipient adverse events and enabling timely public health responses to prevent morbidity and mortality., (Published by Elsevier Inc.)