Results of Two Cases of Pig-to-Human Kidney Xenotransplantation.

BACKGROUND: Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue. METHODS: We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection. RESULTS: The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m2 of body-surface area before transplantation to 62 ml per minute per 1.73 m2 after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m2 in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys. CONCLUSIONS: Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).

Establishment of an orthotopic prostate cancer xenograft mouse model using microscope-guided orthotopic injection of LNCaP cells into the dorsal lobe of the mouse prostate.

BACKGROUND: Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge. METHODS: Under the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described. RESULTS: The DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n = 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma. CONCLUSIONS: This study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.

Reconstruction of the orbital floor using supercritical CO2 decellularized porcine bone graft.

Orbital floor fractures subsequently lead to consequences such as diplopia and enophthalmos. The graft materials used in orbital floor fractures varied from autografts to alloplastic grafts, which possess certain limitations. In the present study, a novel porcine bone matrix decellularized by supercritical CO2 (scCO2), ABCcolla® Collagen Bone Graft, was used for the reconstruction of the orbital framework. The study was approved by the institutional review board (IRB) of Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH). Ten cases underwent orbital floor reconstruction in KMUH in 2019. The orbital defects were fixed by the implantation of the ABCcolla® Collagen Bone Graft. Nine out of ten cases used 1 piece of customized ABCcolla® Collagen Bone Graft in each defect. The other case used 2 pieces of customized ABCcolla® Collagen Bone Graft in one defect area due to the curved outline of the defect. In the outpatient clinic, all 10 cases showed improvement of enophthalmos on CT (computerized tomography) at week 8 follow-up. No replacement of implants was needed during follow-ups. To conclude, ABCcolla® Collagen Bone Graft proved to be safe and effective in the reconstruction of the orbital floor with high accessibility, high stability, good biocompatibility, low infection rate and low complication rate.

How common are complications following polypropylene mesh, biological xenograft and native tissue surgery for pelvic organ prolapse? A secondary analysis from the PROSPECT trial.

OBJECTIVE: To report complication rates following prolapse surgery using polypropylene mesh inlay, polypropylene mesh kit, biological collagen xenografts and native tissue repairs. DESIGN: Secondary analysis of the PROSPECT randomised controlled trial and cohort study. SETTING: Thirty-five UK hospitals. POPULATION: A total of 2632 women undergoing anterior and/or posterior vaginal prolapse repair. METHODS: Event rates were calculated for all complications. Analysis was by treatment received. MAIN OUTCOME MEASURES: IUGA/ICS classification of complications and validated patient reported outcome measures. RESULTS: At baseline, 8.4% of women had 'generic' pain/discomfort; at 2 years following surgery, there was an improvement in all four groups; however, 3.0% of women developed de novo extreme generic pain. At 24 months de novo vaginal tightness occurred in 1.6% of native tissue, 1.2% of biological xenograft, 0.3% of mesh inlay and 3.6% of mesh kit. Severe dyspareunia occurred in 4.8% of native tissue, 4.2% of biological xenograft, 3.4% of mesh inlay repairs and 13.0% of mesh kits. De novo severe dyspareunia occurred in 3.5% of native tissue, 3.5% of biological xenograft, 1.4% of mesh inlays and 4.8% of mesh kits. Complications requiring re-admission to hospital, unrelated to mesh, affected 1 in 24 women; the most common reasons for re-admission were vaginal adhesions, urinary retention, infection and constipation. CONCLUSIONS: This is the first study to address the complications of vaginal mesh used for prolapse surgery alongside data from both native tissue and biological xenograft. It demonstrates the complexity of assessing pain and that all types of prolapse surgery have low surgical morbidity and a low rate of severe complications. TWEETABLE ABSTRACT: A prospective study of 2362 women undergoing vaginal mesh, xenograft or native tissue repair found low surgical morbidity and low rates of severe complications.

Establishment and characterization of an ovarian yolk sac tumor patient-derived xenograft model.

OBJECTIVE: The lack of appropriate preclinical models of ovarian yolk sac tumor (OYST) is currently hindering the pursuit of new methods of treatment and investigation of the pathogenesis of the disease. We developed and characterized an OYST patient-derived xenograft (PDX) model in this study. METHODS: Tumor fragments from a patient with an OYST were implanted subcutaneously into BALB/c Nude mice. Engrafted xenografts were compared with the original tumor according to histology, immunohistochemistry, humanized identified, and drug efficacy testing with in vivo treatment programs. RESULTS: There was a high degree of histologic and immunohistochemical (IHC) resemblance between the established PDX model and its corresponding human tumors. Bleomycin, etoposide, and cisplatin (JEB) chemotherapy regimens were effective in clinical patients and were effective in the OYST PDX model; therefore, the effect of PDX intervention was consistent with clinical outcomes of OYSTs. CONCLUSION: We have successfully established an OYST PDX model. This OYST model preserves the basic molecular features of the primary human tumor, thereby providing a valuable method to preclinically evaluate new treatments and explore disease pathogenesis.

Collagenated Porcine Heterologous Bone Grafts: Histomorphometric Evaluation of Bone Formation Using Different Physical Forms in a Rabbit Cancellous Bone Model.

Collagenated porcine-derived bone graft materials exhibit osteoconductive properties and the development of different formulations intends to enhance bone regeneration. This study aims to evaluate bone healing in a rabbit cancellous bone defect in response to grafting with different physicochemical forms of heterologous porcine bone. Twenty-six adult male New Zealand White rabbits received two critical size femoral bone defects per animal (n = 52), each randomly assigned to one of the five tested materials (Apatos, Gen-Os, mp3, Putty, and Gel 40). Animals were sacrificed at 15- and 30-days post-surgery. Qualitative and quantitative (new bone, particle and connective tissue percentages) histological analyses were performed. Histomorphometry showed statistically significant differences in all evaluated parameters between mp3 and both Putty and Gel 40 groups, regardless of the timepoint (p < 0.05). Moreover, statistical differences were observed between Apatos and both Putty (p = 0.014) and Gel 40 (p = 0.007) groups, at 30 days, in regard to particle percentage. Within each group, regarding new bone formation, mp3 showed significant differences (p = 0.028) between 15 (40.93 ± 3.49%) and 30 (52.49 ± 11.04%) days. Additionally, intragroup analysis concerning the percentage of particles revealed a significant reduction in particle occupied area from 15 to 30 days in mp3 and Gen-Os groups (p = 0.009). All mp3, Gen-Os and Apatos exhibited promising results in terms of new bone formation, thus presenting suitable alternatives to be used in bone regeneration.

Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice.

Prostate cancer (PCa) patient-derived xenografts (PDXs) are commonly propagated by serial transplantation of "pieces" of tumour in mice, but the cellular composition of pieces is not standardised. Herein, we optimised a microwell platform, the Microwell-mesh, to aggregate precise numbers of cells into arrays of microtissues, and then implanted the Microwell-mesh into NOD-scid IL2γ-/- (NSG) mice to study microtissue growth. First, mesh pore size was optimised using microtissues assembled from bone marrow-derived stromal cells, with mesh opening dimensions of 100×100 µm achieving superior microtissue vascularisation relative to mesh with 36×36 µm mesh openings. The optimised Microwell-mesh was used to assemble and implant PCa cell microtissue arrays (hereafter microtissues formed from cancer cells are referred to as microtumours) into mice. PCa cells were enriched from three different PDX lines, LuCaP35, LuCaP141, and BM18. 3D microtumours showed greater in vitro viability than 2D cultures, but neither proliferated. Microtumours were successfully established in mice 81% (57 of 70), 67% (4 of 6), 76% (19 of 25) for LuCaP35, LuCaP141, and BM18 PCa cells, respectively. Microtumour growth was tracked using live animal imaging for size or bioluminescence signal. If augmented with further imaging advances and cell bar coding, this microtumour model could enable greater resolution of PCa PDX drug response, and lead to the more efficient use of animals. The concept of microtissue assembly in the Microwell-mesh, and implantation in vivo may also have utility in implantation of islets, hair follicles or other organ-specific cells that self-assemble into 3D structures, providing an important bridge between in vitro assembly of mini-organs and in vivo implantation.

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression.

Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

Safety of Irradiated Homologous Costal Cartilage Graft in Cleft Rhinoplasty.

BACKGROUND: Autologous cartilage grafts have a low risk of infection and extrusion in cleft rhinoplasty. However, harvesting autologous cartilage involves donor-site morbidity and increased time under anesthesia. Irradiated homologous costal cartilage grafts may be an effective alternative. METHODS: A retrospective study was performed on patients with a history of cleft lip who underwent rhinoplasty for cleft nasal deformity at Johns Hopkins Hospital from 2009 to 2018. Patients were excluded if their rhinoplasty did not involve a cartilage graft. RESULTS: One hundred sixty-five cleft rhinoplasties (patient age, 2 to 72 years; 52 percent female) were performed. Median follow-up time was 256 days; 30 percent were revision operations. Ninety-six procedures (58 percent) used irradiated homologous costal cartilage grafts, with the remaining using autologous cartilage. Complications resulted from 18 procedures (11 percent), seven (10 percent) involving autologous cartilage and 11 (12 percent) involving irradiated homologous costal cartilage. Most autologous cartilage complications (86 percent) required operative intervention, versus seven of 11 (64 percent) for irradiated homologous costal cartilage. Complications associated with irradiated homologous costal cartilage included infection (n = 5), warping (n = 2), and extrusion (n = 1), while two patients with autologous cartilage experienced collapse and one each experienced resorption, warping, and hypertrophic donor-site scarring. There was no difference between groups regarding complication rate or complications requiring operative intervention (p = 0.3 and p = 0.5, respectively). CONCLUSIONS: Irradiated homologous costal cartilage grafts are equally safe and effective as autologous cartilage for use in cleft rhinoplasty. These grafts are readily available and eliminate donor-site morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Community Hospital Experience With Bovine Tissue in Infected Vascular Fields.

BACKGROUND: Vascular prosthetic graft infections are rare but associated with high morbidity and mortality. Treatment involves removal of the infected graft requiring arteriotomy closure. Previously this was performed with autologous graft, but bovine tissue has increasingly been used. The objective of this paper is to review the community hospital experience with bovine tissue repair in an infected vascular field. MATERIALS AND METHODS: A retrospective review of all cases performed by a single surgeon in a community hospital for infected prosthetic grafts was completed. Sixteen cases were included where bovine tissue was used for repair. Presentation, location of graft, and causative organism were reviewed, and outcomes including reoperation and mortality were recorded. RESULTS: Of the 16 patients, 15 (94%) had positive cultures of the graft. Methicillin-Resistant Staph Aureus was the most commonly isolated organism (50%). There were 3 unplanned reoperations including a revision from below to above knee amputation, drainage of a hematoma, and a wound debridement within the first year. Over the 1 year follow up period, 3 patients died for a mortality of 19%. There were no reinfections during follow-up. DISCUSSION: Prosthetic graft infection is a rare but serious vascular surgery complication. The causative organism has shifted in the last few years to become increasingly drug resistant. Treatment requires excision, and bovine tissue has been demonstrated to provide a safe and durable method of repair.

Simultaneous Perio-endo Surgery with ER:YAG Laser and Bone Xenograft. A Case Report.

Periodontally affected teeth with periapical lesion indicated for periapical surgery have a poor prognosis. Using Er:YAG lasers to perform simultaneous surgery on both defects may increase their survival rate. Preparing a retrograde cavity on affected teeth and obturating it is still a matter of debate among clinicians. The purpose of this case report was to describe the simultaneous use of Erbium-doped Yttrium Aluminium Garnet Er:YAG (2,940 nm) laser in the treatment of periapical granuloma and infraossal defect and the achieved results. The Er:YAG laser was used to perform flap dissection, granulation tissue removal, osteotomy and root-end resection except for initial flap incision and reflection. The cystic cavity was filled with Bio-Oss Collagen® xenograft. Results were followed up for 18 months with the help of radiographic orthopantomographic images. The outcome of this clinical case indicates that the use of Er:YAG laser could be considered a suitable method to perform simultaneous periodontal and endodontic surgery.

ARG1 functions as a tumor suppressor in breast cancer.

Arginase I (ARG1) is a cytosolic enzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The association of ARG1 with cancer has mostly been focused on the ARG1 released by tumor-associated myeloid cells in tumor microenvironment. However, the role of ARG1 expressed in cancer cells is unclear. Here, we showed that the expression of ARG1 in human breast cancer (BC) is related to a good prognosis in BC patients. Overexpression of ARG1 suppresses BC cell proliferation and migration in vitro and xenograft tumor growth and development in mouse models. Furthermore, ARG1 expression down-regulates the expression of p-AKT, leading to the de-activation of AKT signal pathway in BC cells. Thus, our results established that in contrast to the role of ARG1 released from tumor-associated myeloid cells in tumor microenvironment that promotes tumor immune escape, ARG1 expressed in BC cells suppresses AKT signaling pathway and functions as a tumor suppressor.

Generation of foxn1/Casper Mutant Zebrafish for Allograft and Xenograft of Normal and Malignant Cells.

Cell transplantation into immunodeficient recipients is a widely used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a foxn1/Casper mutant zebrafish that is transparent and exhibits T cell deficiency. By employing the line for hematopoietic stem cell (HSC) transplantation (HSCT), we could achieve nonconditioned transplantation. Meanwhile, we found that fetal HSCs from 3 days post fertilization zebrafish embryos produce a better transplant outcome in foxn1/Casper mutants, compared with adult HSCs. In addition to HSCT, the foxn1/Casper mutant is feasible for allografts of myelodysplastic syndrome-like and muscle cells, as well as xenografts of medaka muscle cells. In summary, foxn1/Casper mutants permit the nonconditioned engraftment of multiple cell types and visualized characterization of transplanted cells in vivo.

Generation of GGTA1-/-ß2M-/-CIITA-/- Pigs Using CRISPR/Cas9 Technology to Alleviate Xenogeneic Immune Reactions.

BACKGROUND: Xenogeneic organ transplantation has been proposed as a potential approach to fundamentally solve organ shortage problem. Xenogeneic immune responses across species is one of the major obstacles for clinic application of xeno-organ transplantation. The generation of glycoprotein galactosyltransferase α 1, 3 (GGTA1) knockout pigs has greatly contributed to the reduction of hyperacute xenograft rejection. However, severe xenograft rejection can still be induced by xenoimmune responses to the porcine major histocompatibility complex antigens swine leukocyte antigen class I and class II. METHODS: We simultaneously depleted GGTA1, ß2-microglobulin (ß2M), and major histocompatibility complex class II transactivator (CIITA) genes using clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins technology in Bamma pig fibroblast cells, which were further used to generate GGTA1ß2MCIITA triple knockout (GBC-3KO) pigs by nuclear transfer. RESULTS: The genotype of GBC-3KO pigs was confirmed by polymerase chain reaction and Sanger sequencing, and the loss of expression of α-1,3-galactose, SLA-I, and SLA-II was demonstrated by flow cytometric analysis using fluorescent-conjugated lectin from bandeiraea simplicifolia, anti-ß2-microglobulin, and swine leukocyte antigen class II DR antibodies. Furthermore, mixed lymphocyte reaction assay revealed that peripheral blood mononuclear cells from GBC-3KO pigs were significantly less effective than (WT) pig peripheral blood mononuclear cells in inducing human CD3CD4 and CD3CD8 T-cell activation and proliferation. In addition, GBC-3KO pig skin grafts showed a significantly prolonged survival in immunocompetent C57BL/6 mice, when compared with wild-type pig skin grafts. CONCLUSIONS: Taken together, these results demonstrate that elimination of GGTA1, ß2M, and CIITA genes in pigs can effectively alleviate xenogeneic immune responses and prolong pig organ survival in xenogenesis. We believe that this work will facilitate future research in xenotransplantation.

The use of acellular porcine dermis, hyaluronic acid and polynucleotides in the treatment of cutaneous ulcers: Single blind randomised clinical trial.

Reconstruction of chronic ulcers is often hampered by lack of local tissues and poor general conditions. Conservative approaches with debridement and advanced medications, such as polyurethane foam, stand as mainstays. However, the healing process is often slow, thus increasing the risk for infection or other complications. In such cases, porcine dermis (PD) and polynucleotides-added hyaluronic acid (PAHA) were previously reported to accelerate healing. The aim of the study was to compare the efficacy of PD, PAHA and polyurethane foam in chronic ulcers. Thirty patients were randomly divided into 3 groups: group 1 was treated with advanced medications, group 2 with PD, group 3 with PAHA. Standardised photographs and biopsies were taken before treatment and at 30-day follow-up. Photographs were processed to calculate the wound area. Specimens were stained with Haematoxylin/Eosin, Masson trichrome, and immunohistochemically for CD34, alpha-Smooth Muscle Actin (α-SMA), Collagen types I and III, Ki67. The re-epithelialized area was larger in patients treated with PD and PAHA compared with those treated with polyurethane foam (P < .05 and P < .01, respectively). Specimens from patients treated with PD and PAHA showed a higher number of myofibroblasts (α-SMA+, P < .01), neo-angiogenesis (CD34+, P < .01), proliferating dermal cells (Ki67+, P < .01), proliferating keratinocytes (Ki67+, P < .01) and collagen type 1 deposition (P < .05). No difference was found between PD and PAHA. PD and PAHA proved to be more effective than polyurethane foam in the treatment of chronic ulcers. These approaches are a versatile and reliable option to address such cases.

Implant stability in patients treated with platelet-rich fibrin and bovine bone substitute for alveolar ridge preservation is associated with peripheral blood cells and coagulation factors.

AIMS: The aim of the present study was to assess the association between dental implant stability and peripheral blood cell composition and levels of coagulation factors in patients treated with alveolar ridge preservation with platelet-rich fibrin (PRF) and bovine bone substitute. MATERIALS AND METHODS: Fifty patients were included between 2015 and 2017. PRF was prepared from autologous blood, in which blood cells and coagulation factor levels were measured. PRF and bovine bone were placed in the socket, followed by closure with PRF membrane. Implants were placed 14 (±2.5) weeks postextraction. The implant stability quotient was measured at t = 0, t = 10 days, t = 7 weeks, and t = 17 weeks by resonance frequency analysis. RESULTS: Erythrocyte count was inversely associated with PRF membrane length, but not with implant stability. Conversely, platelet count did not correlate with membrane size but inversely correlated with implant stability at 7 and 17 weeks. In addition, implant stability was directly correlated with levels FXIII (t = 0, p < .01), active von Willebrand factor (VWF; t = 0 and 7 weeks, p < .05), and total VWF (t = 7 weeks, p = .012). CONCLUSION: Implant stability following alveolar ridge preservation with PRF and bovine bone substitute is associated with circulating blood cells and coagulation factors. In particular, fibrin structure, VWF, and FXIII may be important modulators of implant stability.

Developing a xenograft model of human vasculature in the mouse ear pinna.

Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research. We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum. This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies.

Fixation augmentation using titanium cage packing with xenograft in the treatment of tibial plateau fractures.

OBJECTIVES: To evaluate a new surgical technique concerning titanium cage packing with xenograft demineralized bone matrix bovine augmentation in the management of subchondral bone defects associated with tibial plateau fractures. METHODS: All patients underwent plate fixation augmentation using titanium cage packing with xenograft, with the help of digital medical software of Mimics and 3-matic preoperatively. Duration of the surgical procedure, intraoperative bleeding volume, bone union time, quality of reduction and alignment, fracture healing, complications, and functional outcomes based on Oxford knee outcome score were recorded. RESULTS: A total of 18 patients were followed for average 18.1 months (range, 12-24 months). The average radiographic bony union time was 12.8 weeks (range, 11-17 weeks) and full weight bearing time was 13.4 weeks (range, 11-16 weeks) respectively. At one-year follow-up, the mean degrees of knee extension were 2.7° (range, 0-6) and the mean degrees of knee flexion were 122.0° (range, 112-134). The articular step-off was unchanged from 0.9 ±â€¯0.6 mm (range, 0-1.8 mm) to 1.0 ±â€¯0.6 mm (0-1.9 mm) (P = 0.512). All the cases had satisfactory reduction. No secondary loss of reduction was found over the time period studied. Superficial infection was found in one case, and resolved with closed treatment. No implant failures were noted. The average Oxford knee score was 19.9 ±â€¯5.4 (range, 12-30) at the final follow-up. CONCLUSION: Fixation augmentation using titanium cage packing with xenograft augmentation is a safe and effective way to treat the depressed tibial plateau fractures.