Donor Tissue Research Articles

Scleral collagen crosslinking as a promising direction of sclera-strengthening treatment of progressive myopia

The review presents recent research works on new technologies of scleral collagen crosslinking, a promising approach to sclerastrengthening treatment of progressive myopia. We assess the advantages and limitations of a number of experimental techniques of photochemical and medicinal crosslinking of the sclera, as well as donor tissue crosslinking aimed at optimizing the plastic material for sclera-strengthening surgery. Successful experiments and effective first clinical implementation results of the approach can be viewed as the basis for its further improvement and wider introduction of the technology into ophthalmological practice.

Association between Storage Time of Corneal Grafts and Primary Graft Failure in Penetrating Keratoplasty

Purpose: To determine association between storage time of corneal grafts and primary graft failure in Penetrating Keratoplasty (PK). Study Design: Quasi experimental study. Place and Duration of Study: Institute of Ophthalmology, Eye Unit-III, King Edward Medical University, Mayo Hospital, Lahore from June, 2019 to December, 2019. Methods: In this study, 120 patients (between 11 and 30 years of age) diagnosed with keratoconus were enrolled and divided into two groups. Group A comprised individuals who underwent PK with donor tissues stored for 8 to 14 days, while Group B consisted of patients whose donor tissues were stored for a duration not exceeding 7 days. Patients were followed up for three weeks post-operatively. The data was analyzed using SPSS version 19 and stratified for age, gender and primary graft failure. Post stratification RR was calculated with p-value ≤ 0.05 as significant. Results: The mean age of patients in Group A was 21.38 ± 6.29 years and in Group B was19.80 ± 5.81 years. In Group A there were 32 male and 28 female while in Group B there were 29 male and 31 female. In Group A 16(26.7%) patients and in group B, 4 (6.7%) patients had primary graft failure. The risk of primary graft failure was higher in Group A, with RR = 4, p-value < 0.05. Conclusion: The risk of primary graft failure in PK is higher when the storage time of corneal grafts is longer. Hence, minimization of storage time may ensure better success rate of corneal grafting.

Fat-augmented omentum-based construct for breast reconstruction

In the landscape of breast reconstruction, autologous tissue procedures have provided viable alternatives, albeit restricted by donor site morbidity and patient-specific anatomical considerations, including donor tissue availability and surgical history. Amidst these challenges, a novel approach has emerged - the fat-augmented omentum-based construct for breast reconstruction. This comprehensive review endeavors to explore the historical evolution, anatomical considerations, surgical techniques, clinical outcomes, and future directions of the fat-augmented omentum-based approach in breast reconstruction. The omental fat-augmented free flap (O-FAFF) offers a promising choice for patients who might not be appropriate candidates for conventional autologous reconstruction methods due to low BMI, previous surgeries compromising traditional donor sites, or insufficient adipose tissue volume. Operative techniques for O-FAFF involve a coordinated team approach, with simultaneous mastectomy and laparoscopic omentectomy. The omentum is shaped within an acellular dermal matrix casing, allowing for precise control of reconstruction dimensions. In addition, utilizing the omentum with fat grafting effectively restores the natural breast volume. Clinical outcomes of O-FAFF reconstruction have shown promise, with patients reporting natural-looking and soft-feeling reconstructed breasts. However, challenges such as accurate tissue volume estimation and potential complications remain, highlighting the need for further research and refinement of the technique. Overall, O-FAFF represents a significant advancement in breast reconstruction, offering a promising alternative to traditional methods. Continued investigation and clinical experience will be instrumental in establishing O-FAFF as a standard of care, ultimately improving outcomes for a wide range of patients undergoing breast reconstruction.

The Biomechanical, Biochemical, and Morphological Properties of 19 Human Cadaveric Lower Limb Tendons and Ligaments: An Open-Access Data Set

Background: Methodological heterogeneity hinders data comparisons across isolated studies of tendon and ligament properties, limiting clinical understanding and affecting the development and evaluation of replacement materials. Purpose: To create an open-access data set on the morphological, biomechanical, and biochemical properties of clinically important tendons and ligaments of the lower limb, using consistent methodologies, to enable direct tendon/ligament comparisons. Study Design: Descriptive laboratory study. Methods: Nineteen distinct lower limb tendons and ligaments were retrieved from 8 fresh-frozen human cadavers (5 male, 3 female; aged 49-65 years) including Achilles, tibialis posterior, tibialis anterior, fibularis (peroneus) longus, fibularis (peroneus) brevis, flexor hallucis longus, extensor hallucis longus, plantaris, flexor digitorum longus, quadriceps, patellar, semitendinosus, and gracilis tendons; anterior cruciate, posterior cruciate, medial collateral, and lateral collateral ligaments; and 10 mm–wide grafts from the contralateral quadriceps and patellar tendons. Outcomes included morphology (tissue length, ultrasound-quantified cross-sectional area [CSAUS], and major and minor axes), biomechanics (failure load, ultimate tensile strength [UTS], failure strain, and elastic modulus), and biochemistry (sulfated glycosaminoglycan [sGAG] and hydroxyproline contents). Tissue differences were analyzed using mixed-model regression. Results: There was a range of similarities and differences between tendons and ligaments across outcomes. A key finding relating to potential graft tissue suitability was the comparable failure loads, UTS, CSAUS, sGAG, and hydroxyproline present between hamstring tendons (a standard graft source) and 5 tendons not typically used for grafting: fibularis (peroneus) longus and brevis, flexor and extensor hallucis longus, and flexor digitorum longus tendons. Conclusion: This study of lower limb tendons and ligaments has enabled direct comparison of morphological, biomechanical, and biochemical human tissue properties—key factors in the selection of suitable graft tissues. This analysis has identified 6 potential new donor tissues with properties comparable to currently used grafts. Clinical Relevance: This extensive data set reduces the need to utilize data from incompatible sources, which may aid surgical decisions (eg, evidence to expand the range of tendons considered suitable for use as grafts) and may provide congruent design inputs for new biomaterials and computational models. The complete data set has been provided to facilitate further investigations, with the capacity to expand the resource to include additional outcomes and tissues.

Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation

BackgroundIntrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA.MethodsHuman EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis.ResultsWe successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor.ConclusionsDue to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA.

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

Transplantation of stem cell-derived β-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach is the long differentiation timeline that generates a heterogeneous population of pancreatic endocrine cells. To address this limitation, an inducible lentiviral overexpression system of mature β-cell markers was introduced into human induced-pluripotent stem cells (hiPSCs). Following the selection of the successfully transduced hiPSCs, the cells were treated with doxycycline in the pancreatic progenitor induction medium to support their transition toward the pancreatic lineage. Cells cultured with doxycycline presented the markers of interest, NGN3, PDX1, and MAFA, after five days of culture, and glucose-stimulated insulin secretion assays demonstrated that the cells were glucose-responsive in a monolayer culture. When cultured as a spheroid, the markers of interest and insulin secretion in a static glucose-stimulated insulin secretion assay were maintained; however, insulin secretion upon consecutive glucose challenges was limited. Comparison to human fetal and adult donor tissues identified that although the hiPSC-derived spheroids present similar markers to adult insulin-producing cells, they are functionally representative of fetal development. Together, these results suggest that with optimization of the temporal expression of these markers, forward programming of hiPSCs towards insulin-producing cells could be a possible alternative for islet transplantation.

“Bubble Behind Iris” Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes

Purpose: Performing Descemet membrane keratoplasty (DMEK) in vitrectomized eyes can be challenging, owing to the compromised stability of the iris–lens diaphragm. This study presents a “bubble behind iris” technique in DMEK to achieve a shallower anterior chamber in vitrectomized and pseudophakic eyes. Methods: The patients with vitrectomized eyes who underwent DMEK between October 2022 and March 2023 were enrolled in this study. Following the insertion of the donor tissue into the anterior chamber, a 30-gauge blunt cannula was used to introduce an air bubble posterior to the iris. The depth of the anterior chamber was confirmed before unfolding the graft. Subsequently, the air bubble was carefully replaced with balanced salt solution insertion using the blunt cannula, and the anterior chamber was filled with gas for graft attachment. Results: This study included 3 eyes of 3 patients (3 men; mean age 62.3 ± 8.5 years). The best spectacle corrected visual acuity and central corneal thickness improved in all eyes with no notable complications. Conclusions: The “bubble behind iris” technique is a straightforward and minimally invasive approach for maintaining an optimal anterior chamber depth during DMEK in vitrectomized and pseudophakic eyes.

Donor Limb Functional Restoration via a Novel Clinical Care Pathway following Fibula Free Flap Harvest for Head and Neck Reconstruction.

Patients undergoing head and neck skeletal reconstruction (HNR) often require free tissue transfer from the extremities to ensure proper restoration of form and function. This requires a team-based, highly reliable medical system centered around the patient needs. Surgical intervention across multiple sites and harvesting of donor tissue results in short- and long-term physical impairments. There is a paucity of research objectively measuring impairments resulting from the graft donor site. There is a lack of research that objectively measures impairments and protocols for the management of these patients postoperatively. Patients undergo little, if any, formal approach to dealing with the vast impairments, which are sequelae to this surgery. This leads to large discrepancies in proposed functional progressions, return to duty timelines, and utilization of rehabilitative resources. At a major military medical center, an innovative clinical care pathway for patients undergoing HNR using free tissue transfer was implemented using a multidisciplinary model that focuses on early engagement with rehabilitation. This model, paired with a single surgery, will attempt to return service members to duty months earlier than the traditional approach. This report describes the conceptual framework and implementation of a new criteria-based, multidisciplinary clinical care pathway for HNR patients. The collaboration amongst the multidisciplinary care team has optimized the holistic health of the patient and communication with their support network, yielding faster return to normalization of daily life activities. The long-term goal is to further develop and formalize this pathway to best serve this patient population.

Mesenchymal Stromal Cell-Based Products: Challenges and Clinical Therapeutic Options.

Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells or embryonic stem cells. However, ATMP heterogeneity may impact product identity and potency, and, consequently, clinical trial outcomes. In this review, we discuss these topics and the need to establish minimal criteria regarding the manufacturing of MSCs so that these innovative therapeutics may be better positioned to contribute to the advancement of regenerative medicine.

Transcriptome RNA-Seq Analysis of Normal and Keratoconus Corneal Epithelium

Background: Keratoconus (KTCN) is a progressive eye condition characterised by thin, misshapen corneas arising in the teens or early twenties, and can cause visual disability. While this can be corrected with glasses or contact lenses, collagen cross-linking of the cornea slows disease progression. In advanced disease, patients undergo transplantation of the corneal epithelial layer with normal donor tissue. The cause of KTCN is unknown, but there is evidence for both environmental and genetic bases. Material and Methods: RNA-Seq data from published work by Kabza et al., 2017, was used to investigate the pathology of cornea tissue, analysing twenty-five KTCN and twenty-five non-KTCN samples from RNA-seq experiments. Principal component analysis plots were used to identify how characteristics impact development of keratoconus. Results: The findings show that KTCN is more common in teenagers and young adults, and all 25 KTCN samples were for individuals under 30 years old. Principal component analysis also showed that approximately 35% of samples were from individuals who rubbed their eyes. It also showed that KTCN is more common in males, representing over 65% of samples. Differential expression analysis of RNA-sequencing data was used to identify differentially expressed genes, downregulated genes were found to be enriched in many pathways, including cytokinecytokine receptor interaction pathways, and played a role in keratoconus development. Conclusion: Upregulated genes were enhanced in six pathways, including the peroxisome pathway. A potential relation was found between defects in peroxisome and keratoconus development. Overexpression of peroxisome genes increases phytanic acid levels, and causes Zellweger spectrum, affecting the cornea and potentially leading to keratoconus.

Keratoplasty - an Overview of the Methods and their Perioperative Management

Corneal transplantation can be divided into two groups: penetrating and lamellar keratoplasty. Newer minimally invasive procedures have emerged over the years, to improve the visual outcome and reduce complications. This article summarizes the different procedures, their indications and complications, and outlines the pre-, peri- and postoperative management in a clinical setting.Corneal transplantation is the most commonly performed transplantation of donor tissue in modern medicine. In the last years a shift away from penetrating keratoplasty (PK) towards minimally invasive lamellar operative techniques, associated with less complications, can be observed. The Descemet membrane endothelial keratoplasty (DMEK) is used to treat endothelial corneal pathologies and has overtaken the PK to become the most commonly performed form of keratoplasty. Preparation and identification of possible risk-factors are essential preoperative steps to reduce peri- and postoperative complications of keratoplasties. If corneal graft rejection occurs, early and maximum therapy is crucial for graft survival. Laser-assisted techniques offer different advantages in lamellar and penetrating keratoplasty but are not very cost-efficient.

Transcriptome profiling of immune rejection mechanisms in a porcine vascularized composite allotransplantation model.

Vascularized composite allotransplantation (VCA) offers the potential for a biological, functional reconstruction in individuals with limb loss or facial disfigurement. Yet, it faces substantial challenges due to heightened immune rejection rates compared to solid organ transplants. A deep understanding of the genetic and immunological drivers of VCA rejection is essential to improve VCA outcomes. Heterotopic porcine hindlimb VCA models were established and followed until reaching the endpoint. Skin and muscle samples were obtained from VCA transplant recipient pigs for histological assessments and RNA sequencing analysis. The rejection groups included recipients with moderate pathological rejection, treated locally with tacrolimus encapsulated in triglycerol-monostearate gel (TGMS-TAC), as well as recipients with severe end-stage rejection presenting evident necrosis. Healthy donor tissue served as controls. Bioinformatics analysis, immunofluorescence, and electron microscopy were utilized to examine gene expression patterns and the expression of immune response markers. Our comprehensive analyses encompassed differentially expressed genes, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways, spanning various composite tissues including skin and muscle, in comparison to the healthy control group. The analysis revealed a consistency and reproducibility in alignment with the pathological rejection grading. Genes and pathways associated with innate immunity, notably pattern recognition receptors (PRRs), damage-associated molecular patterns (DAMPs), and antigen processing and presentation pathways, exhibited upregulation in the VCA rejection groups compared to the healthy controls. Our investigation identified significant shifts in gene expression related to cytokines, chemokines, complement pathways, and diverse immune cell types, with CD8 T cells and macrophages notably enriched in the VCA rejection tissues. Mechanisms of cell death, such as apoptosis, necroptosis and ferroptosis were observed and coexisted in rejected tissues. Our study provides insights into the genetic profile of tissue rejection in the porcine VCA model. We comprehensively analyze the molecular landscape of immune rejection mechanisms, from innate immunity activation to critical stages such as antigen recognition, cytotoxic rejection, and cell death. This research advances our understanding of graft rejection mechanisms and offers potential for improving diagnostic and therapeutic strategies to enhance the long-term success of VCA.

Investigating the Use of Companion Animal Donor Tissue Banks

Research and education continue to be highly reliant on the use of animal cadavers and tissues. However, due to the damaging impact on animal life, contribution to animal suffering, and lack of translatability of laboratory animal research to humans, alternatives must be investigated. An ethically sourced alternative is the use of non-human animal donor tissue banks, which involves the donation of companion animal cadavers and tissues. A scoping review of current research on the opinions pertaining to companion animal donor tissue banks was conducted using the Queen’s University Omni database. 62 articles were screened and three met the scoping review inclusion criteria. Collectively, these publications displayed positive attitudes among pet owners and veterinarian students towards companion animal cadaver and tissue donation. A common concern raised amongst participants of the studies was the inability to bury or cremate their pets if they were to donate them to tissue banks for research. In conclusion, this scoping review examined trends in the opinions of participants from several studies regarding the use of non-human animal donor tissue banks. Overall, companion animal tissue banks offer an ethical alternative to laboratory animal use and a more reliable model for translatability to humans. The gaps in knowledge outlined in this scoping review direct future research involving the collection of professional perspectives, including veterinarians and researchers.

Exploring the Potential of an Eye Tissue Donor Reporting App in Enhancing the Procurement of Corneal Donors: Mixed Methods Observational Study.

The availability of donated eye tissue saves and enhances vision in transplant recipients; however, the current demand for tissue surpasses the available supply. Corneal donor shortages lead to increased wait times, delayed surgeries, prolonged visual impairment, and increased inconvenience to patients requiring eye tissue transplantation. A web-based application was previously developed to facilitate easy and intuitive submission of potential donor information. The primary objectives of this study were to assess health care professionals' attitudes toward the potential application and evaluate its effectiveness based on user feedback and donor registrations through the application. Researchers used a mixed methods approach, commencing with a literature review to identify challenges associated with donor procurement. Stakeholder interviews were conducted to gauge health care professionals' perspectives regarding the application. User feedback was collected through questionnaires, surveys, and interviews to assess the application's usability and impact. An assessment of the reported potential donors and questionnaire responses were analyzed. The final version of the application successfully reported 24 real cornea donors. Among 64 health care providers who used the application to communicate about potential donors, 32 of them submitted trial entries exclusively for testing purposes. The remaining 8 health care professionals reported potential donors; however, these individuals did not meet the donor qualification criteria. The majority of participants found the application user-friendly and expressed their readiness to use it in the future. Positive ratings were assigned to the layout, appearance, purpose, and specific features of the application. Respondents highlighted the automatic sending of notifications via SMS text messages and the integration of all necessary documents for donor qualification and tissue collection as the most valuable functions of the application. The study indicates that donor reporting applications offer promising solutions to enhance tissue donor procurement. This application streamlined the reporting process, reduced paperwork, facilitated communication, and collected valuable data for analysis.

LC-MS Lipidomic Analysis of Macrophages

Currently, an increasing incidence of cardiovascular diseases is observed in the population. Factors contributing to their development are obesity and pro-inflammatory processes occurring in the adipose tissue. Macrophages, cells of the non-specific immune system, which can be divided into pro-inflammatory and anti-inflammatory, play a significant role in these processes. For a better understanding of these phenomena, it is necessary to analyze the lipidome of macrophages of the two mentioned groups. The presented work was focused on the optimization of selected parameters of the LC-MS method for the analysis of 71 lipids from 16 lipid classes. Best results were achieved with column Acquity UPLC BEH C18 (1.7 µm, 2.1 mm × 100 mm) operating at the flow rate of 300 μL min–1 and temperature of 55 °C. The optimal desolvation temperature was 350 °C and the gradient elution started at 0 % of solvent B in the mobile phase. Retention dependencies were characterized for individual lipid classes. They were successfully fitted with a linear model (R2 > 0.99) and subsequently used to confirm the accuracy of lipid identification. The optimized LC-MS method was also used to analyze the real samples of macrophages isolated from the adipose tissue of kidney donors. Samples were provided by Institute for Clinical and Experimental Medicine. The principal component analysis gave insight into the division of macrophages according to their type. The volcano plot showed a significant increase in the concentration of five lipids in the case of pro-inflammatory macrophages.

Characterization of heterogeneous skin constructs for full thickness skin regeneration in murine wound models

An autologous heterogeneous skin construct (AHSC) has been developed and used clinically as an alternative to traditional skin grafting techniques for treatment of cutaneous defects. AHSC is manufactured from a small piece of healthy skin in a manner that preserves endogenous regenerative cellular populations. To date however, specific cellular and non-cellular contributions of AHSC to the epidermal and dermal layers of closed wounds have not been well characterized given limited clinical opportunity for graft biopsy following wound closure. To address this limitation, a three-part mouse full-thickness excisional wound model was developed for histologic and macroscopic graft tracing. First, fluorescent mouse-derived AHSC (mHSC) was allografted onto non-fluorescent recipient mice to enable macroscopic and histologic time course evaluation of wound closure. Next, mHSC-derived from haired pigmented mice was allografted onto gender- and major histocompatibility complex (MHC)-mismatched athymic nude mouse recipients. Resulting grafts were distinguished from recipient murine skin via immunohistochemistry. Finally, human-derived AHSC (hHSC) was xenografted onto athymic nude mice to evaluate engraftment and hHSC contribution to wound closure. Experiments demonstrated that mHSC and hHSC facilitated wound closure through production of viable, proliferative cellular material and promoted full-thickness skin regeneration, including hair follicles and glands in dermal compartments. This combined macroscopic and histologic approach to tracing AHSC-treated wounds from engraftment to closure enabled robust profiling of regenerated architecture and further understanding of processes underlying AHSC mechanism of action. These models may be applied to a variety of wound care investigations, including those requiring longitudinal assessments of healing and targeted identification of donor and recipient tissue contributions.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

SDPR expression in human trabecular meshwork and its potential role in racial disparities of glaucoma

In order to identify how differential gene expression in the trabecular meshwork (TM) contributes to racial disparities of caveolar protein expression, TM dysfunction and development of primary open angle glaucoma (POAG), RNA sequencing was performed to compare TM tissue obtained from White and Black POAG surgical (trabeculectomy) specimens. Healthy donor TM tissue from White and Black donors was analyzed by PCR, qPCR, immunohistochemistry staining, and Western blot to evaluate SDPR (serum deprivation protein response; Cavin 2) and CAV1/CAV2 (Caveolin 1/Caveolin 2). Standard transmission electron microscopy (TEM) and immunogold labeled studies were performed. RNA sequencing demonstrated reduced SDPR expression in TM from Black vs White POAG patients’ surgical specimens, with no significant expression differences in other caveolae-associated genes, confirmed by qPCR analysis. No racial differences in SDPR gene expression were noted in healthy donor tissue by PCR analysis, but there was greater expression as compared to specimens from patients with glaucoma. Analysis of SDPR protein expression confirmed specific expression in the TM regions, but not in adjacent tissues. TEM studies of TM specimens from healthy donors did not demonstrate any racial differences in caveolar morphology, but a significant reduction of caveolae with normal morphology and immuno-gold staining of SDPR were noted in glaucomatous TM as compared to TM from healthy donors. Linkage of SDPR expression levels in TM, POAG development, and caveolar ultrastructural morphology may provide the basis for a novel pathway of exploration of the pathologic mechanisms of glaucoma. Differential gene expression of SDPR in TM from Black vs White subjects with glaucoma may further our understanding of the important public health implications of the racial disparities of this blinding disease.

Skin Substitutes: Filling the Gap in the Reconstructive Algorithm

Background: Skin substitutes play a crucial role in wound care by actively modulating the wound healing process, promoting angiogenesis, and protecting the integrity of the native extracellular matrix. Consequently, surgeons have increasingly recognized these resources as excellent complements to improve reconstructive outcomes. This review focuses on the author’s experience using these biomaterials in complex cases, highlighting the benefits they bring to patient care. Methods: A literature review was conducted to evaluate the regenerative properties of skin substitutes and their applicability in head and neck, upper and lower extremities, and trunk reconstruction. Results: The reviewed literature, along with the authors’ experience, supports the adjunct use of skin substitutes in various reconstructive situations. Combining them with skin grafts improves resulting skin quality and may also enhance donor site healing. They have proven to be effective in addressing chronic venous ulcers, traumatic wounds with limited donor tissues for coverage, extensive burns, diabetic foot ulcers, and oncological resections in the face and scalp. Furthermore, combining them with autologous tissue shows promising results in achieving stable closure. Conclusions: Incorporating skin substitutes in complex reconstructive scenarios offers multiple benefits. Their regenerative properties and ability to modulate the healing process contribute to enhanced outcomes and reduced overall costs.

A novel intralamellar semi‐bioresorbable keratoprosthesis—Part A: Design conception, material perspective, and device manufacturing

AbstractCorneal diseases are a significant cause of visual impairment and blindness. The first‐line treatment for corneal opacity is penetrating keratoplasty (human donor cornea transplantation). At present, keratoprosthesis (KPro), an artificial cornea, is the last resort for correcting end‐stage corneal blindness and is usually supported by donor tissue. This article describes a new intralamellar tissue‐free KPro design concept and its preparation method. Wherein, an injection‐molding route is adopted to create a mechanically and structurally stable near‐KPro geometry using a photo‐polymerized poly(2‐hydroxyethyl methacrylate) (pHEMA) with 4% Bisphenol A dimethacrylate (BisMA) crosslinked (PC4) hydrogel composition. Prior to this, the physico‐mechanical properties of crosslinked hydrogels matching corneal tissue are identified, and the surface morphological characteristics of silk cocoon membranes are ascertained in choosing suitable KPro materials. Cytocompatibility tests on PC4 and silk‐incorporated PC4 hydrogels using rabbit corneal fibroblast cell‐line evidenced enhancement in cell growth on silk‐PC4 surfaces. Furthermore, near KPro geometry is surface‐profiled to create a one‐of‐a‐kind design with clear optics and a silk‐bioactivated composite‐based haptic‐flange hydrogel network containing site‐specific submillimeter‐scale perforations to improve tissue integration. Considering this unique KPro geometry, the optic‐haptic‐flange construct is a tissue‐free semi‐bioresorbable hydrogel device presumed to provide stability under the influence of intraocular pressure (IOP) and eyelid shear. Through this study, it is identified new KPro materials facilitate significant cytocompatibility while complimented with site‐specific novel design would offer tissue ingrowth with gradual resorption of silk, leaving behind a stable intralamellar tissue integrated with hydrogel when implanted in the corneal niche.