Search Results (19)

For decades, regeneration of alveolar bone defects has depended on traditional grafting options, such as autogenous/allogenic grafts or allografts. Recently, extracted teeth was introduced as an alternative graft source. Tooth autografts are being used and have gained significant attention due to their biocompatibility, osteoconductivity, osteoinductivity, and osteogenic properties. Furthermore, tooth allografts have potential to act as natural biocomposites for oral regeneration procedures and might be advantageous options in near future. Recent advances in tooth banking, including cryopreservation, can serve to maintain bioactivity and to improve the safety, viability, and regenerative potential of teeth. They might be revolutionary in oral surgery, offering a more sustainable solution to the growing demand for bone regeneration procedures. Nevertheless, challenges such as immunogenic responses, ethical issues, and regulatory constraints persist. Ongoing research and technological innovation continue to address these problems. To date, the success rates of tooth autografts are promising, and they are regarded as a reliable option in clinical practice, with predictable outcomes in alveolar ridge preservation, sinus augmentation, periodontal regeneration, guided bone regeneration (GBR), and endodontic surgery by providing natural scaffolds for cell integration and bone remodeling. However, the scientific literature on tooth allografts is lacking. Therefore, this review aimed to comprehensively evaluate the scientific literature for comparing the properties of tooth grafts with other grafting options, in terms of processing techniques, and various clinical applications, positioning them as versatile biocomposites for the future, bridging material science and regenerative dentistry. Furthermore, possible applications of allogenic tooth grafts and overcoming current limitations are also discussed. Full article

Operating under septic conditions poses significant challenges in vascular surgery. Infection is a serious risk when handling synthetic vessel prostheses and is one of the most dreaded complications. In the event of graft infection, an infection-resistant alternative is necessary. Cryopreserved vascular allografts offer a suitable alternative to replace an infected vessel or a section of a synthetic graft. However, there are no international guidelines for the preparation, storage, and thawing of such vessel grafts. Here, we aimed to investigate the mechanical properties of human cryopreserved arteries across multiple scales, ranging from nanonewton to newton forces and identify the optimal cryogenic storage duration. Human arterial allograft samples were frozen in a slow, controlled process and stored at −80 °C. One native and four cryopreserved samples were examined during a six-month-long period. Dimethyl-sulphoxide was used as a cryoprotectant. The mechanical properties of fresh and stored samples were explored in uniaxial ring tests and nanoindentation. We found no significant changes in the multi-scale mechanical properties during the examination period. Our results indicate that the cryopreserved vascular allografts are mechanically stable for up to six months under cryogenic conditions; hence, they represent ideal samples in vascular surgery. Full article

Tissue selective ultrasonic debridement is a new method of debriding chronic wounds that prepares the wound for advanced tissue application. This article presents the case of an 89-year-old woman with a chronic nonhealing wound to her lateral distal leg. The wound had a significant amount of biofilm and fibrous slough. Conservative treatment consisting of debridement and multilayer compression was attempted for 4 weeks. After 4 weeks, the patient was taken to the operating room for tissue selective ultrasonic debridement with placement of cryopreserved human skin allograft. With local wound care and multiple applications of graft, the chronic wound fully epithelialized. This study highlights the use of tissue selective ultrasonic debridement combined with cryopreserved human skin allograft to successfully heal a chronic wound. To our knowledge, this method of operative debridement and application of graft has not been documented in the literature. Full article

The biological products used in orthopedics include musculoskeletal allografts—such as bones, tendons, ligaments, and cartilage—as well as biological therapies. Musculoskeletal allografts support the body’s healing process by utilizing preserved and sterilized donor tissue. These allografts are becoming increasingly common in surgical practice, allowing patients to avoid more invasive procedures and the risks associated with donor site morbidity. Bone grafting is one of the most frequently used procedures in orthopedics and traumatology. Biologic approaches aim to improve clinical outcomes by enhancing the body’s natural healing capacity and reducing inflammation. They serve as an alternative to surgical interventions. While preliminary results from animal studies and small-scale clinical trials have been promising, the field of biologics still lacks robust clinical evidence supporting their efficacy. Biological therapies include PRP (platelet-rich plasma), mesenchymal stem cells (MSCs)/stromal cells/progenitor cells, bone marrow stem/stromal cells (BMSCs), adipose stem/stromal cells/progenitor cells (ASCs), cord blood (CB), and extracellular vesicles (EVs), including exosomes. The proper preservation and storage of these cellular therapies are essential for future use. Preservation techniques include cryopreservation, vitrification, lyophilization, and the use of cryoprotective agents (CPAs). The most commonly used CPA is DMSO (dimethyl sulfoxide). The highest success rates and post-thaw viability have been achieved by preserving PRP with a rate-controlled freezer using 6% DMSO and storing other cellular treatments using a rate-controlled freezer with 5% or 10% DMSO as the CPA. Extracellular vesicles (EVs) have shown the best results when lyophilized with 50 mM or 4% trehalose to prevent aggregation and stored at room temperature. Full article

Given progressive population ageing and the increase in the number of patients with comorbidities, the management of chronic and/or hard-to-heal wounds (HHWs) nowadays represents a common problem in many clinical settings. In these cases, standard strategies may not be sufficient. Autologous grafting represent the gold standard for permanent wound closure, but is almost never realized when the skin loss is extensive/the patient is young. The grafting of homologous skin/dermal tissue procured from cadaver donors (i.e., allografting) represents the best alternative, especially when the dermal component is lost. This request supports the activities of skin bank establishments (including donor screening, skin procurement, processing, storage, and distribution) that are regulated by specific guidelines and need to continuously meet quality standard requirements. The aim of this work is to both give specific insights of all the procedures implied in allograft preparation as well as an overview of their practical application in the treatment of different HHWs. The particular characteristics of each skin/dermal allograft released by Siena Skin Bank (cryopreserved/glycerol-preserved skin/de-epidermized dermis, acellular lyophilized de-epidermized dermis/reticular dermis) are also discussed. The exemplificative series of HHWs managed in the Dermatology Department of Siena were classified according their etiology into post-traumatic, vascular (arterial/venous/mixed/lymphatic), inflammatory, surgical, and heat/chemical burns. Globally, the clinical advantages obtained include: acceleration of healing process, pain sparing, resistance to bacterial contamination, dermal regeneration (instead of scarring), and better aesthetic–functional outcome. Full article

Background: Human placental allografts are widely used to promote wound healing. Placental (or amniotic membrane/umbilical cord) allografts are placed along the neurovascular bundles during radical prostatectomy to improve continence and erectile function recovery. It is unknown whether placental allografts impact biochemical recurrence (BCR). Methods: This was a single-surgeon retrospective study of 566 robotic radical prostatectomies performed from April 2015 to March 2021. The patients were divided into three groups: the negative control, Brand A, and Brand B. Brand A and Brand B were both cryopreserved amniotic membrane (CAM) allografts. A total of 324 cases were included for BCR Kaplan–Meier and risk-adjusted multivariate analyses (362 for continence analysis). In vitro analyses were performed to determine the effect of CAM allografts on prostate cancer (PCa) cell line growth. Results: For propensity score-matched analysis (adjusting for pre-operative PSA, tumor stage, Gleason Grade, and margin status), (1) the allograft groups did not show differences in time to BCR vs. the negative control group (p = 0.7), and (2) combined allograft treatment groups showed better continence recovery vs. the negative controls (p = 0.01). In vitro, placental allografts reduced PCa cell line growth in co-culture assays. Conclusions: cryopreserved AM allografts (combined or individual brands) did not show a significant effect on BCR but improved continence recovery for PCa patients. Full article

Background: Osteoarthritis is a chronic disorder that affects the synovial joints by the progressive loss of articular cartilage. In the hip, the largest weight-bearing joint, the deterioration of articular cartilage and acetabular labrum can cause pain, diminishing the quality of life for patients. This study presents changes in reported pain scales from patients who received Wharton’s jelly applications to cartilage deterioration in the hip from the observational retrospective repository at Regenative Labs. Methods: Sixty-nine patients were selected based on inclusion criteria with patient-reported pain scales, including the Numeric Pain Rating Scale and the Western Ontario and McMaster University Osteoarthritis Index, collected at the initial application, 30, and 90-day follow-up visits. Thirteen patients received a second allograft application and had additional follow-up visits at 120 and 180 days. Results: Five of the six scales used showed a statistically significant improvement in average scores across the cohort. The greatest improvements were observed in the NPRS with a 31.36% improvement after 90 days and a 44.64% improvement for patients with two applications after 180 days. The minimal clinically important difference (MCID) was also calculated to determine the perceived value of care for each patient with 44.9% of patients exceeding the MCID and 78.3% reporting at least one level of improvement. Conclusions: The positive outcomes for the patients in this cohort suggest WJ to be a promising alternative care option for patients with structural tissue degeneration in the hip refractory to the current standard of care. Full article

The COVID-19 pandemic has precipitously changed the practice of transplanting fresh allografts. The safety measures adopted during the pandemic prompted the near-universal graft cryopreservation. However, the influence of cryopreserving allogeneic grafts on long-term transplant outcomes has emerged only in the most recent literature. In this review, the basic principles of cell cryopreservation are revised and the effects of cryopreservation on the different graft components are carefully reexamined. Finally, a literature revision on studies comparing transplant outcomes in patients receiving cryopreserved and fresh grafts is illustrated. Full article

Recent advances in anticancer treatment have significantly improved the survival rate of young females; unfortunately, in about one third of cancer survivors the risk of ovarian insufficiency and infertility is still quite relevant. As the possibility of becoming a mother after recovery from a juvenile cancer is an important part of the quality of life, several procedures to preserve fertility have been developed: ovarian surgical transposition, induction of ovarian quiescence by gonadotropin-releasing hormone agonists (GnRH-a) treatment, and oocyte and/or ovarian cortical tissue cryopreservation. Ovarian tissue cryostorage and allografting is a valuable technique that applies even to prepubertal girls; however, some patients cannot benefit from it due to the high risk of reintroducing cancer cells during allograft in cases of ovary-metastasizing neoplasias, such as leukemias or NH lymphomas. Innovative techniques are now under investigation, as in the construction of an artificial ovary made of isolated follicles inserted into an artificial matrix scaffold, and the use of stem cells, including ovarian stem cells (OSCs), to obtain neo-folliculogenesis and the development of fertilizable oocytes from the exhausted ovarian tissue. This review synthesizes and discusses these innovative techniques, which potentially represent interesting strategies in oncofertility programs and a new hope for young female cancer survivors. Full article

Immobilization using external or internal splints is a standard and effective procedure to treat minor skeletal fractures. In the case of major skeletal defects caused by extreme trauma, infectious diseases or tumors, the surgical implantation of a bone graft from external sources is required for a complete cure. Practical disadvantages, such as the risk of immune rejection and infection at the implant site, are high in xenografts and allografts. Currently, an autograft from the iliac crest of a patient is considered the “gold standard” method for treating large-scale skeletal defects. However, this method is not an ideal solution due to its limited availability and significant reports of morbidity in the harvest site (30%) as well as the implanted site (5–35%). Tissue-engineered bone grafts aim to create a mechanically strong, biologically viable and degradable bone graft by combining a three-dimensional porous scaffold with osteoblast or progenitor cells. The materials used for such tissue-engineered bone grafts can be broadly divided into ceramic materials (calcium phosphates) and biocompatible/bioactive synthetic polymers. This review summarizes the types of materials used to make scaffolds for cryo-preservable tissue-engineered bone grafts as well as the distinct methods adopted to create the scaffolds, including traditional scaffold fabrication methods (solvent-casting, gas-foaming, electrospinning, thermally induced phase separation) and more recent fabrication methods (fused deposition molding, stereolithography, selective laser sintering, Inkjet 3D printing, laser-assisted bioprinting and 3D bioprinting). This is followed by a short summation of the current osteochondrogenic models along with the required scaffold mechanical properties for in vivo applications. We then present a few results of the effects of freezing and thawing on the structural and mechanical integrity of PLLA scaffolds prepared by the thermally induced phase separation method and conclude this review article by summarizing the current regulatory requirements for tissue-engineered products. Full article

The aim of this study was to compare concentrations of endogenous N-acylethanolamine (NAE) lipid mediators—palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA)—in fresh, decontaminated, cryopreserved, and freeze-dried amniotic membrane (AM) allografts, thereby determining whether AM’s analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chromatography–tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPAR-α receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher values for all NAEs were detected in cryopreserved samples compared to fresh tissue before decontamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of the PPAR-α receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue, was found in cryopreserved, but not freeze-dried, AM. Results indicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects. This means that cryopreserved AM allografts released for transplant purposes before the expected expiration (usually 3–5 years) will still show a strong analgesic effect. The same situation was confirmed for AM lyophilized after one year of storage. This work thus contributed to the clarification of the analgesic effect of NAEs in AM allografts. Full article

The indications for cryopreserved allografts in aortic valve replacement are still debatable. We aim to identify factors influencing early and long-term durability of the aortic homograft and to define subgroups of patients with an improved long-term quality of life, survival, and freedom from structural valve degeneration (SVD). We evaluated our series of 210 patients who underwent allograft implantation with a retrospective cohort study design over a period of 20 years. Endpoints were overall mortality, cardiac mortality related to SVD, the incidence of SVD, reoperation, and a composite endpoint comprising major adverse cardiac and cerebrovascular events (MACCEs), which includes cardiac death both related and not related to SVD, subsequent aortic valve surgery, new or recurrent infection of implanted allograft, recurrent aortic regurgitation, rehospitalization for heart failure, an increase in New York Heart Association (NYHA) class of ≥1, or cerebrovascular events. The primary indication for surgery was endocarditis (48%), which was also a predisposing factor for increased cardiac mortality. Overall mortality was 32.4% with a 27% incidence of SVD and mortality associated with SVD of 13.8%. Reoperation occurred in 33.8% and MACCEs in 54.8%. Long-term NYHA functional class and echocardiographic parameters improved over time. Statistical analysis demonstrated that root replacement technique and adult age were protective factors for SVD. We found no statistically significant difference in the clinical outcomes analyzed between women of childbearing age who had children after surgery and the rest of the women. The cryopreserved allograft is still a valid option in aortic valve replacement, providing acceptable durability and clinical outcomes with optimal hemodynamic performance. SVD is influenced by the implantation technique. Women of childbearing age might have additional benefits from this procedure. Full article

This Institutional Review Board (IRB)-approved retrospective observational protocol aims to report the safety and efficacy of birth tissue allografts applied in 38 patients with treatment-resistant sacroiliac (SI) joint pain. The research methodology consisted of an observational recording of the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC), which measure pain, stiffness, and physical function. No adverse events or adverse reactions were observed in the 38 patients. Statistically significant improvements in NPRS and WOMAC scores of the affected SI joint were reported after 90 days. The observational data suggests that Wharton’s jelly allograft applications are safe, minimally invasive, and efficacious. They may present an alternative to surgery for patients who fail conservative and procedural management of pain originating from chondral cartilage degeneration of the SI joint. Full article

The application of tissue-engineering technology to wound healing has become an option for the treatment of diabetic foot ulcers (DFU). A comparative, prospective study was conducted to assess the efficacy of a cryopreserved allograft of human epidermal keratinocytes (Epifast) to enhance wound healing in granulating DFU. Eighty patients were assigned to receive Epifast (n = 40) or Standard Care (SC) treatment (n = 40). The Epifast group displayed a shorter duration of the epithelialization phase (3.5 ± 4 vs. 6.4 ± 3.6 weeks, p < 0.05) and upon the entire wound healing process than the SC group (10 ± 5.7 vs. 14.5 ± 8.9 weeks, p < 0.05), reaching wound closure at 16 and 30 weeks, respectively. The Kaplan–Meier analysis revealed that Epifast group patients were 50% more likely than the SC to heal wounds faster (Cox-hazards ratio of 0.5, 95% CI = 0.3–0.8, p < 0.0001; Likelihood Ratio of 7.8. p < 0.05). Patients in the control group displayed a slower healing as the Saint Elian (SEWSS) severity grade increased (group differences of 0.6, 3.8, and 4.3 weeks for grades I, II, and III, respectively). DFW treated with Epifast displayed a shorter time to complete re-epithelialization than wounds treated with standard care. Full article

Background: The aim of this study was to evaluate the effectiveness of positron emission tomography/computed tomography with [¹⁸F]-fludeoxyglucose (FDG-PET/CT) and radiomics analysis in detecting differences between the native aorta and the abdominal aortic allograft after the total eradication of infection in patients undergoing infected graft removal and in situ reconstruction with cryopreserved allografts. Methods: Between January 2008 and December 2018, 56 vascular reconstructions with allografts have been performed at our department. The present series included 12 patients undergoing abdominal aortic in situ reconstruction with cryopreserved allografts. During the follow-up, all patients underwent a total-body [¹⁸F]FDG PET/CT with subsequent radiomics analysis. In all patients, a comparative analysis between the data extracted from native aorta and cryopreserved graft for each patient was performed. Results: All patients were male with a mean age of 72.8 years (range 63–84). Mean duration of follow-up was 51.3 months (range 3–120). During the follow-up, 2 patients (16.7%) needed a redo allograft-related surgical intervention. Overall, the rate of allograft dilatation was 33.3%. No patient had a redo infection during the follow-up. Radiomics analysis showed a different signature of implanted allograft and native aorta. Comparative analysis between the native aortas and cryopreserved allografts (dilated or not) showed several statistical differences for many texture features. Conclusions: The higher metabolic activity of allografts could indicate a state of immune-mediated degeneration. This theory should be proven with prospective, multicentric studies with larger sample sizes. Full article