Xenograft Group Research Articles

Radiographic changes after alveolar ridge preservation using autogenous raw tooth particles versus xenograft: A prospective controlled clinical trial.

The use of extracted teeth has been introduced as an option for bone grafting. However, the current method requires special machines and solutions, posing significant time and cost. The aim of this study was to evaluate the clinical performance of autogenous raw tooth particles (RTP), a grafting material made from a ground tooth using basic equipment, for alveolar ridge preservation. Twenty-three patients (12 study/11 control), having 14 and 13 sites were included for the study and control groups (commercially available xenograft), respectively. Radiographic measurements were taken at the baseline and the 4-month follow-up appointment. Furthermore, a questionnaire survey concerning the general preference of the type of graft to receive (if needed), before and after knowing the price, was distributed at the completion of the procedure for patients to answer. Alveolar ridge width change was -1.03 ± 0.64 and -0.84 ± 0.35 for the study and the control groups, respectively. Regarding the height, the study group showed a buccal and lingual change of -0.66 ± 0.48 and -0.78 ± 0.81, respectively, while this was -0.78 ± 0.56 and -0.9 ± 0.41 for the xenograft group. There was no statistically significant difference between the groups. Patients preferred the raw tooth particles over other grafting materials (p = .01). No core biopsies were taken to evaluate bone formation, which should be done in future studies. Within its limitations, the current study demonstrated that RTP graft could be an alternative graft for bone augmentation, offering a new cost-effective option for clinicians when available.

Comparative Effectiveness of an Autologous Dentin Matrix for Alveolar Ridge Preservation.

An urgent issue is the preservation or reconstruction of the volume of bone tissue in planning and surgical treatment in the fields of medicine, such as traumatology, orthopedics, maxillofacial surgery and dentistry. After tooth extraction, resorption of the bone tissue of the alveolar crest of the jaws occurs, which must either be further eliminated by performing additional operations or using osteoplastic material for socket preservation at the extraction stage. Background and Objectives: The aim of the study was a comparative analysis of various osteoplastic materials used to preserve the volume of bone tissue in the preimplantation period. Materials and Methods: As part of the study, 80 patients were treated, who underwent socket preservation using xenografts, plasma enriched with growth factors, an autologous dentin matrix (ADM) and hydroxyapatite. Results: The results of the treatment 16 weeks after removal were comprehensively analyzed using a morphometric analysis of the bone's volume, cone beam tomography and morphological examination of burr biopsy specimens, as well as by determining the stability of the installed implant at different stages of treatment. Conclusions: The lowest level of bone tissue resorption according to the CBCT data was noted in the ADM and xenograft groups. It should be noted that the use of osteoplastic material in jaw surgery when reconstructing alveolar defects is an essential procedure for preventing the atrophy of bone tissue.

Superior Capsular Reconstruction Using an Acellular Dermal Xenograft or Allograft Improves Shoulder Function but Is Associated with a High Graft Failure Rate.

Objectives: The purpose of the present study was to evaluate clinical and functional outcomes, graft integrity rate and progression of osteoarthritis after superior capsular reconstruction (SCR) at short-term follow-up. Methods: Consecutive patients that underwent SCR using an acellular dermal xeno- or allograft between May 2018 and June 2020 for the treatment of irreparable posterosuperior rotator cuff tears were included. Shoulder function (American Shoulder and Elbow Surgeons [ASES] score), pain (Visual Analog Scale [VAS] for pain) and active shoulder range of motion (ROM) were evaluated preoperatively and after a minimum of 24 months postoperatively. Isometric strength was measured at follow-up and compared to the contralateral side. Magnetic resonance imaging was performed to evaluate graft integrity and osteoarthritis progression (shoulder osteoarthritis severity [SOAS] score). Results: Twenty-two patients that underwent SCR using a xeno- (n = 9) or allograft (n = 13) were evaluated 33.1 ± 7.2 months postoperatively. Four patients in the xenograft group underwent revision surgery due to pain and range of motion limitations and were excluded from further analysis (revision rate: 18.2%). Shoulder function (ASES score: 41.6 ± 18.8 to 72.9 ± 18.6, p < 0.001), pain levels (VAS for pain: 5.8 ± 2.5 to 1.8 ± 2.0, p < 0.001) and active flexion (p < 0.001) as well as abduction ROM (p < 0.001) improved significantly from pre- to postoperatively. Active external rotation ROM did not improve significantly (p = 0.924). Isometric flexion (p < 0.001), abduction (p < 0.001) and external rotation strength (p = 0.015) were significantly lower in the operated shoulder compared to the non-operated shoulder. Ten shoulders demonstrated a graft tear at the glenoid (n = 8, 44.4%) or humerus (n = 2, 11.1%). Graft lysis was observed in seven shoulders (38.9%). The graft was intact in one shoulder (5.6%), which was an allograft. A significant progression of shoulder osteoarthritis was observed at follow-up (SOAS score: 42.4 ± 10.1 to 54.6 ± 8.4, p < 0.001). Conclusions: At short-term follow-up, SCR using an acellular dermal xeno- or allograft resulted in improved shoulder function and pain with limitations in active external rotation ROM and isometric strength. Graft failure rates were high and osteoarthritis progressed significantly. Level of Evidence: Retrospective cohort study, Level III.

Impact of Interproximal Features on Marginal Bone Level Changes of Autograft, Allograft, and Xenograft after Functional Loading: A Retrospective Study

Abstract Aim: This study aims to investigate the marginal bone level changes (MBLCs) concerning interproximal features of posterior implant-supported single crowns using different bone grafts. Materials and Methods: This retrospective study included 27 patients requiring 46 dental implants using autograft, allograft, or xenograft between January 2007 and December 2016. MBLCs were assessed using digital periapical radiographs at 3 months (T1), 12–15 months (T2), and 21–24 months (T3) after prosthesis delivery. The influence of interproximal features, such as embrasure surface area, emergence angle, and horizontal distance to adjacent teeth/implants, was assessed. Secondarily, age, gender, diabetes and smoking, arch distribution, implant locations, implant characteristics, average gonial angle, antagonist type, clinical crown-to-fixture ratio, retention method, and nearby tooth/implant were considered. Wilcoxon signed-rank test, Mann–Whitney U tests, and Kruskal–Wallis tests were employed with statistical significance set at a P value of &lt;0.05. Results: The results revealed that mean MBLCs at T3–T1 were similar (autograft 0.5 ± 0.47 mm, allograft 0.51 ± 0.35 mm, and xenograft 0.57 ± 0.42 mm). There were significant increases in MBLCs associated with EA ≤ 30° in autograft (P = 0.04), and HD ≤ 3 mm in allograft (P = 0.03). Mesial/distal MBLCs showed no significant differences, except in cases with HD ≤ 3 mm in the distal area of autograft (P = 0.03). Regarding secondary factors, significant differences in MBLCs emerged between autograft and xenograft in the molar area (P = 0.03), and between premolar and molar areas within the xenograft group (P = 0.01). Conclusion: This study concludes that interproximal features, EA ≤ 30° and HD ≤ 3 mm, markedly influenced MBLCs for specific types of bone grafts. Furthermore, MBLCs exhibited a direct relationship with the posterior placement of dental implants.

Texture Analysis of Hard Tissue Changes after Sinus Lift Surgery with Allograft and Xenograft

In the realm of dental surgery, implants are essential for replacing missing teeth. To facilitate implant placement, techniques such as bone grafting and sinus lifts are utilized to augment the volume of atrophied alveolar bone in candidates for dental implants. Typically, patients undergo a period of recovery following bone grafts before proceeding with implant placement. This study investigates the efficacy of Cone Beam Computed Tomography (CBCT) in measuring the residual bone volume and assessing bone quality after the healing phase. A texture analysis was conducted on CBCT scans from 42 patients requiring maxillary sinus lift reconstruction. These patients were categorized into two groups based on the type of grafting material used: Xenograft or allograft. The study analyzed the distribution of various texture parameters and conducted a Mann-Whitney U test to identify significant statistical differences between the groups. Results indicated non-normal distributions for specific variables such as Area_S(1,0) and S(1,0)SumOfSqs, while others like S(1,0)Entropy displayed normal distributions. The findings revealed no significant statistical differences in the primary outcomes between the xenograft and allograft groups. However, the average values of the gray shades of pixels in the allograft group were statistically significantly higher compared to the xenograft group, suggesting differences in bone texture post-procedure.

Autologous leucocyte and platelet rich in fibrin (L-PRF) - is it a competitive solution for bone augmentation in maxillary sinus lift? A 6-month radiological comparison between xenografts and L-PRF.

Much of the research published involves using artificial products, like xenografts and resorbable collagen membranes, after a prior Cone Beam Computer Tomography (CBCT) investigation. Nowadays, more accessible access, less financial costs, a biological approach, and faster healing are objectives that surround this procedure. Leucocytes and platelets rich in Fibrin (L-PRF) are a natural component with a high concentration of growth factors. Due to its regenerative properties and lack of complications, it is used in several medical fields, like orthopedics, dermatology, and oral surgery. This retrospective study aims to compare results in bone height and volume obtained through external sinus lift, either by using xenografts or autologous plasma rich in fibrin, by evaluating the quantity of new bone formation from a radiological point of view. Fifty-eight Caucasian patients were included in this retrospective study; 48 were submitted to xenograft procedure, and 10 were selected for L-PRF grafting material with simultaneous implant placement. Lack of clinical and histological studies performed on patients with L-PRF surgeries limited us in choosing a larger group for the radiological analysis. CBCT evaluation was performed before surgery and 6 months after. All patients selected for the study presented good general and oral health, acute oral and sinus infections excluded; smoking and periodontal disease were also criteria of exclusion. Two operators performed the measurements in pre-established landmarks in different time frames. The two independent groups were compared with the Wilcoxon rank-sum test for quantitative data. Qualitative characteristics were described as counts and percentages. All analyses were performed in an R environment for statistical computing and graphics. Mean bone height gain in the xenograft group in the regions was as follows: 7.44 for the anterior landmark, 12.14 for the median and 8.28 for the distal. The mean group height gained for the L-PRF group was 0.1 anteriorly, -0.18 for the median measurement, and 0.23 distally. We obtained excellent overall reliability for all the height measurements between the two operators. Further studies must be conducted to establish new sets of surgical protocols in case L-PRF alone is found to be a reliable, stable, biological alternative to the well-documented xenografts in external sinus lifts. Radiological results, although promising, must be further applied in long term clinical survival of the implants in the grafted sites. Also, studies combining L-PRF in conjunction with xenograft might bring improved clinical results in terms of reduced postoperative complications and accelerated healing.

The response of human osteoblasts on bovine xenografts with and without hyaluronate used in bone augmentation

The aim of the in vitro study was to asses the effect of hyaluronate in conjunction with bovine derived xenografts on the viability, proliferation on day 4, 7 and 10, expression of early osteogenic differentiation marker Alkaline phosphatase on day 14 and 21, collagen, calcium deposition on day 14, 21 and 28 and cellular characteristics, as assessed through live cell image analysis, confocal laser scanning microscopy and scanning electron microscopy, in primary human osteoblasts compared to three bovine xenografts without hyaluronate. All experiments were performed in triplicates. Data were compared between groups and timepoints using one-way analysis of variance (ANOVA). Bonferroni post hoc test were further used for multiple comparison between groups (p < .05) An increase in cell viability (p < .05) and enhanced ALP activity was observed in all xenografts. Specimens containing hyaluronate showed a highest significant difference (23755 ± 29953, p < .0001). The highest levels of calcium (1.60 ± 0.30) and collagen (1.92 ± 0.09, p < .0001) deposition were also observed with hyaluronate loaded groups. The osteoblasts were well attached and spread on all xenograft groups. However, a higher number of cells were observed with hyaluronate functionalized xenograft (76.27 ± 15.11, (p < .0001) in live cell image analysis and they migrated towards the graft boundaries. The biofunctionalization of xenografts with hyaluronate improves their in vitro performance on human osteoblasts. This suggests that hyaluronate might be able to improve the bone regeneration when using such xenografts.

Comparative proteomics reveal the humoral immune rejection of pearl oyster Pinctada fucata to xenograft from Pinctada maxima

To investigate the mechanism underlying immune rejection in pearl oyster Pinctada fucata following allograft (P. fucata mantle pieces) and xenograft (P. maxima mantle pieces) transplantations, we analyzed serum samples collected at multiple time points (6, 12, 24, 48, 96, 144, and 192 h) after transplantation using a proteomics approach. We identified 2127 proteins with high confidence according to the selected peptides (false discovery rate = 0.01), among which 1148 exhibited quantitative differences. Functional enrichment analysis revealed significant changes in protein functional categories, including signal transduction, translation, cytoskeleton, and post-translational modifications. Immune-related proteins, such as the ubiquitin-conjugating enzyme E2, apoptosis-linked gene, heat shock protein, and apoptosis inhibitor 5 were associated with allografts and xenografts. Notably, the PI3K-Akt signaling, focal adhesion, and extracellular matrix (ECM)-receptor interaction pathways were enriched among upregulated proteins (xenograft vs. allograft), while the ribosome pathway was enriched among downregulated proteins. These findings suggest that implantation stress may affect protein biosynthesis or activate multiple molecular pathways involved in key immune proteins. Furthermore, the xenograft group demonstrated greater sensitivity in recognizing and responding to foreign substances compared to the allograft group. This heightened responsiveness enabled the xenograft group to rapidly activate humoral immune factors, which triggered the signaling pathway responsible for suppressing the inflammatory response. This study provides novel insights into the immune reactions of host oysters to grafted mantle pieces, particularly xenografts, and may offer strategies to improve xenograft transplantation technologies in the pearl culture industry.

Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence in a Murine Model of Soft-Tissue Sarcomas.

ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for fluorescence-guided surgery of sarcomas. To date, studies using ABY-029 have occurred in tumors naïve to chemotherapy (CTx) and radiation therapy (RTx), although these neoadjuvant therapies are frequently used for sarcoma treatment in humans. The goal of this study was to evaluate the impact of CTx and RTx on tumor EGFR expression and ABY-029 fluorescence of human soft-tissue sarcoma xenografts in a murine model. Immunodeficient mice (n = 98) were divided into five sarcoma xenograft groups and three treatment groups - CTx only, RTx only, and CTx followed by RTx, plus controls. Four hours post-injection of ABY-029, animals were sacrificed followed by immediate fluorescence imaging of ex vivo adipose, muscle, nerve, and tumor tissues. Histological hematoxylin and eosin staining confirmed tumor type, and immunohistochemistry staining determined EGFR, cluster of differentiation 31 (CD31), and smooth muscle actin (SMA) expression levels. Correlation analysis (Pearson's correlation coefficients, r) and linear regression (unstandardized coefficient estimates, B) were used to determine statistical relationships in molecular expression and tissue fluorescence between xenografts and treatment groups. Neoadjuvant therapies had no broad impact on EGFR expression (|B|≤ 7.0, p ≥ 0.4) or on mean tissue fluorescence (any tissue type, (|B|≤ 2329.0, p ≥ 0.1). Mean tumor fluorescence was significantly related to EGFR expression (r = 0.26, p = 0.01), as expected. Results suggest that ABY-029 as an EGFR-targeted, fluorescent probe is not negatively impacted by neoadjuvant soft-tissue sarcoma therapies, although validation in humans is required.

Clinical and radiological outcomes between superior capsule reconstruction using allografts or xenografts: a 2-year retrospective comparison study

BackgroundTreating symptomatic, massive, irreparable rotator cuff tears remains challenging and controversial. Superior capsule reconstruction (SCR) using the tensor fascia lata has shown promising clinical results; however, due to donor site morbidity, interest in SCR using other grafts has increased. Yet, no studies have compared allografts with xenografts. In addition, the clinical results of graft tears remain controversial. This study compared the clinical and radiological outcomes of SCR between those with allografts and xenografts. MethodsSixty-seven patients who had undergone SCR with allografts or xenografts between January 2016 and December 2020 were included in this retrospective study. Furthermore, 62 patients were evaluated 2 years postsurgery, with five patients excluded due to loss to follow-up or conversion to reverse shoulder arthroplasty. The Constant, American Shoulder and Elbow Surgeons (ASES), and visual analog scale (VAS) scores, range of motion, and radiological outcomes were evaluated before the surgery and at 6 and 24 months after surgery. ResultsThe graft tear rate was 23.08% in the allograft group and 42.86% in the xenograft group at 6 months after surgery; at 2 years postsurgery, the gap further widened to 32.43% and 64.00%, respectively, showing a significant difference. The graft in the allograft group was thicker than that in the xenograft group, and there were significant differences on the humeral side and in the midsubstance area. The allograft group showed significantly better VAS, Constant, and ASES scores than the xenograft group 2 years postsurgery. However, the difference in clinical outcomes between the two groups did not surpass minimal clinically important differences (MCID). ConclusionAlthough ASCR using xenografts had significantly lower clinical outcome than allografts, this difference did not reach MCID. ASCR using xenografts showed higher graft tear rates than allografts. Even with partial tears, better results were obtained if the graft continuity was maintained. Additionally, after surgery, the xenograft showed less thickness than the allograft and resulted in more tears, specifically in the midsubstance area.

Critical-size defects reconstruction with four different bone grafts associated with e-PTFE membrane: Ahistomorphometric experimental invivo study.

The goal of this study was to assess the newly formed bone and the remnant biomaterial by comparing four different bone grafts used to treat critical-size defects, associated or not with the non-resorbable membrane. Two calvaria critical-size bone defects were created in 50 male Wistar rats. They were divided into blood (G1), autogenous (G2), bioglass (G3), hydroxyapatite (G4), and xenograft (G5) groups, associated or not with e-PTFE. The experimental periods were 15 and 45 days. Sections were prepared for histomorphometric assessment. All data were analyzed by the mixed-effects model with multiple comparisons (significance level, p < .05). A similar level of new bone was observed for all groups, associated with a high level of vascularization. G1 and G2 ensured sovereignty over the greater quantity of new bone. A non-significant result was reported comparing groups with and without membranes. No significant result was found between the experimental synthetic biomaterials (G3 and G4). G5L achieved 22.0% of new bone after 45 days (p > .05). All groups had a stable volume of biomaterial kept in the short term (p > .05). G2 was the best material for new bone formation and final volume of biomaterial, followed by G4 < G5 < G3. Thus, it is possible that G4 had a better degradation profile among the experimental groups. The best results were found in the autogenous group, with higher resorption and integration; non-significative new bone was found among the experimental groups; and the regeneration of critical bone defects using an e-PTFE barrier did not present significant results on new bone formation.

Radiographic texture analysis of the hard tissue changes following socket preservation with allograft and xenograft materials for dental implantation: a randomized clinical trial.

This study aimed to assess the hard tissue changes following socket preservation with allograft and xenograft materials for dental implantation by texture analysis (TA) using cone-beam computed tomography (CBCT). This prospective clinical trial was conducted on 25 patients who required the extraction of carious mandibular posterior teeth and their subsequent replacement with dental implants. The patients were categorized into three groups: (I) no socket preservation, (II) socket preservation with xenograft material, and (III) socket preservation with allograft material. Four months after tooth extraction, the patients were recalled for preoperative assessment before dental implantation, and CBCT scans were obtained (Kvp:110, mA:1.94, S:3.6). MaZda software was used to compare homogeneity, contrast, and texture complexity on axial CBCT sections among the three groups. Significant differences existed among the three groups in all parameters (P < 0.05) except for the mean correlation parameter (P > 0.05). The results showed no significant difference between the no graft and xenograft groups regarding contrast and differential (dif.) entropy (P > 0.05). Also, no significant difference was found between the xenograft and allograft groups regarding the dif. variance and also between the no graft and allograft groups regarding the inverse difference moment(InvDfMom) and dif. variance parameters (P > 0.05). All other pairwise comparisons revealed significant differences (P < 0.05). TA can be used for the quantification of radiographic changes of bone following socket preservation and potentially accelerate the process of decision-making for dental implant treatment.

Effects of rhBMP-2 with various carriers on maxillofacial bone regeneration through computed tomography evaluation

BackgroundrhBMP-2 is regarded as the most potent osteoinductive growth factor, and it has been used in the oral cavity with different carriers. The purpose of this study is to evaluate the bone-regenerative effect of rhBMP-2 delivered with different carrier systems through three-dimensional cone beam computed tomography analysis.MethodA total of 112 patients underwent oral surgery with rhBMP-2 application (Group 1, n = 53) or without rhBMP-2 application (Group 2, n = 59). Group 1 was divided into 3 groups according to carriers, rhBMP-2 with allograft (Group 1–1, n = 34), rhBMP-2 with xenograft (Group 1–2, n = 5), and rhBMP-2 with absorbable collagen sponge (Group 1–3, n = 14). Cone beam computed tomography scans were taken before surgery (T0) 6 months after surgery (T1). The volume of defects was measured through the three-dimensional image analysis tool.ResultsThe average bone regeneration rate of Group 1 was significantly greater than that of Group 2. Within Group 1, the group that used allograft as a carrier (Group 1–1) showed significantly higher bone regeneration rates than the group that used absorbable collagen sponge as a carrier (Group 1–3).ConclusionThe use of rhBMP-2 after oral surgery results in a superior bone regeneration rate compared to not using rhBMP-2, and its efficacy depends on the carriers it is used with. Allograft affects bone regeneration more than absorbable collagen sponge when it is carried with rhBMP-2. Therefore, the appropriate use of rhBMP-2 with suitable bone grafting materials is useful for promoting postoperative bone regeneration in oral surgery.

Success of Xenografts in Alveolar Ridge Preservation Based on Histomorphometric Outcomes.

Different xenograft approaches in alveolar ridge preservation (ARP) are essential to understand relative to their histomorphometric outcomes. Therefore, the aim of this study involved studying biomaterials of a xenograft nature that are used in ARP procedures, to compare the different approaches and evaluate their efficacy in relation to histomorphometric data. An electronic search was completed using the databases: Ovid (Medline), Google Scholar and Wiley Online Library, including a hand search for relevant articles and grey literature. Only randomised controlled trials, using xenograft biomaterials for alveolar ridge preservation procedures involving human studies, dated from 2010-2022 were included in the review. An initial search yielded 4918 articles, after application of the eligibility criteria, 18 studies were deemed eligible for inclusion in the systematic review. The two main xenograft groups found were of bovine origin and of porcine origin. The main histomorphometric outcomes evaluated included new bone percentage (N.B%) and residual graft percentage (R.G%). The mean N.B% for the bovine and porcine groups were 33.46% and 39.63% respectively and the mean R.G% for the bovine and porcine groups were 19.40% and 18.63% respectively. The current evidence suggests that the two main xenograft biomaterials used in ARP procedures after tooth extraction, which are of bovine and porcine origin, displayed effectiveness in producing new bone.

Comparative evaluation of the effectiveness of bioresorbable collagen membrane in combination with deproteinized bovine bone matrix xenograft (DBBM), and advanced platelet rich fibrin membrane in combination with deproteinized bovine bone matrix xenograft for periodontal regeneration

Introduction: Periodontitis is a chronic, multifactorial, inflammatory disease that leads to gradual loss of bone and periodontal attachment. Thus, periodontal surgery is required according to severity of diseases. The goal of periodontal reconstructive surgery is to regenerate soft and hard tissues destroyed during periodontal disease. Aim: To compare the effectiveness of bioresorbable collagen membrane in combination with Deproteinized Bovine Bone Matrix xenograft (group A); and Advanced Plasma rich fibrin(A-PRF) membrane in combination with Deproteinized Bovine Bone Matrix xenograft (group B) in the treatment of human infrabony defects. Methods: This randomised controlled trial will be carried out at the periodontics outpatient department. We will choose 24 patients with moderate to advanced chronic periodontitis who are otherwise systemically healthy. Infrabony defects will be treated by open flap debridement using bovine-derived xenograft and bioresorbable collagen membrane (group A) and open flap debridement using bovine-derived xenograft and A-PRF after the completion of first therapy (group B). At baseline and six months after undergoing periodontal surgery, probing pocket depth, clinical attachment level, radiographic bone fill, gingival recession, oral hygiene status, and gingival health will be measured. Expected results: It is suggested that Bioresorbable Collagen Membrane in combination with Deproteinized Bovine Bone Matrix xenograft will show better results as compared to Advanced Platelet Rich Fibrin Membrane with Deproteinized Bovine Bone Matrix Xenograft. Clinical trial registry of India (CTRI): REF/2023/05/066732. Protocol version: v1 (12/05/23)

CDC23 knockdown suppresses the proliferation, migration and invasion of liver cancer via the EMT process.

Liver cancer (LC) is a malignant tumour that is associated with high mortality rates worldwide. Cell division cycle 23 (CDC23) acts as an oncogene in papillary thyroid cancer. In addition, epithelial-mesenchymal transition (EMT) is frequently involved in the malignant metastasis of various cancer types. Therefore, we hypothesized that CDC23 may regulate the malignant biological behaviours of LC cells through EMT. Proliferation, colony formation and Transwell assays, western blotting and xenograft experiments were performed. The results of the present study showed that CDC23 was highly expressed in LC cell lines. In addition, it was found via multiple in vitro assays that CDC23 knockdown reduced the proliferation, migration and invasion of LC cell lines. Finally, an in vivo study confirmed that CDC23 knockdown inhibited the growth of xenograft LC in nude mice. More importantly, the changes in the levels of EMT-related marker proteins were analysed in the sh-CDC23 group compared with the sh-NC group of cells and xenografts. E-cadherin was upregulated, and N-cadherin and vimentin were significantly downregulated after CDC23 silencing. Taken together, these results revealed that the knockdown of CDC23 inhibits the progression of LC by regulating EMT and that CDC23 may be a novel therapeutic target for LC.

Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects

ABSTRACT Decellularized scaffolds are promising biomaterials for tissue and organ reconstruction; however, strategies to effectively suppress the host immune responses toward these implants, particularly those without chemical crosslinking, remain warranted. Administration of mesenchymal stem cells is effective against immune-mediated inflammatory disorders. Herein, we investigated the effect of isogeneic abdominal adipose-derived mesenchymal stem/stromal cells (ADMSCs) on xenogeneic biomaterial-induced immunoreactions. Peripheral bronchi from pigs, decellularized using a detergent enzymatic method, were engrafted onto tracheal defects of Brown Norway (BN) rats. BN rats were implanted with native pig bronchi (Xenograft group), decellularized pig bronchi (Decellularized Xenograft), or Decellularized Xenograft and ADMSCs (Decellularized Xenograft+ADMSC group). In the latter group, ADMSCs were injected intravenously immediately post implantation. Harvested graft implants were assessed histologically and immunohistochemically. We found that acute rejections were milder in the Decellularized Xenograft and Decellularized Xenograft+ADMSC groups than in the Xenograft group. Mild inflammatory cell infiltration and reduced collagen deposition were observed in the Decellularized Xenograft+ADMSC group. Additionally, ADMSC administration decreased CD8+ lymphocyte counts but increased CD163+ cell counts. In the Decellularized Xenograft+ADMSC group, serum levels of vascular endothelial growth factor and IL-10 were elevated and tissue deposition of IgM and IgG was low. The significant immunosuppressive effects of ADMSCs illustrate their potential use as immunosuppressive agents for xenogeneic biomaterial-based implants.

Abstract 5423: AI powered quantification of mitotic rate in H&amp;E stained tissue detects significant differences between treatment groups of preclinical pancreas cancer xenografts

Abstract Background: Mitotic rate is a readout routinely used for characterization of tumor samples. Standard methods to quantify cell division include manual pathologist counts based on hematoxylin and eosin (H&amp;E) staining and either manual or automated assessment of immunohistochemistry (IHC) staining using phospho-histone H3 (pHH3). These suffer the drawbacks of high inter-pathologist variability in the case of H&amp;E assessment and time inefficiency and false positive calls in case of pHH3 staining. Aiming to overcome these issues, we developed a mitosis detection model based on H&amp;E-stained tissue sections alone. Methods: To develop and evaluate the model, we used 1032 H&amp;E-stained tissue sections (156 used for model training) of pre-clinical pancreas cancer xenografts originating from mice that have undergone a series of experiments conducted to examine the pharmacodynamic effect of several anti-cancer protocols. We trained (i) a tissue segmentation model (segmenting tissue regions into ‘carcinoma’, ‘stroma’, ‘necrosis’, and ‘other’) and (ii) a segmentation model for pixel-level mitosis detection (segmenting ‘mitosis’ vs. ‘non-mitosis’). Regions predicted as mitosis were post-processed to represent individual dividing cells. The tissue segmentation model served as a filter to predict mitotic rate for carcinoma tissue areas only, which has not been accounted for in previous AI-based methods for mitotic rate prediction on H&amp;E tissue. To evaluate the model on detecting mitotic events, the model was compared against a 5-pathologist consensus of mitotic count. The mitotic rates predicted by the model were used to infer differences between treatment groups (various treatments and dosages vs. control). Results: The mitosis detection model for quantifying rates of cell division in carcinoma regions of H&amp;E-stained tissue sections showed a notable agreement with the 5-pathologist mitotic count consensus (Pearson correlation 0.92). Furthermore, the model correlated well with mitosis counts based on pHH3 IHC staining (Pearson correlation 0.78), which were available for 63 cases. Finally, when used to characterize the entire CDX cohort, the case level mitotic rate predicted by the model showed significant differences between treatment groups in line with or better than using a pHH3 IHC stain. Conclusion: This study demonstrates the efficacy and scalability of AI-based models for the quantification of mitotic rate based on H&amp;E-stained tissue alone, presenting a time- and cost-efficient approach that also mitigates inter-annotator variability. Citation Format: Sharon Ruane, Lukas Ruff, Brian Reichholf, Christina Aigner, Emil Barbuta, Stephan Tietz, Olivér Atanaszov, Rosemarie Krupar, Simon Schallenberg, Maximilian Alber, Francesca Trapani, Frederick Klauschen. AI powered quantification of mitotic rate in H&amp;E stained tissue detects significant differences between treatment groups of preclinical pancreas cancer xenografts. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5423.

Effect of Porcine- and Bovine-Derived Xenografts with Hydroxypropyl Methylcellulose for Bone Formation in Rabbit Calvaria Defects

In this study, hydroxypropyl methylcellulose (HPMC) was mixed with particle-type xenografts, derived from two different species (bovine and porcine), to increase the manipulability of bone grafts and compare the bone regeneration ability. Four circular defects with a diameter of 6 mm were formed on each rabbit calvaria, and the defects were randomly divided into three groups: no treatment (control group), HPMC-mixed bovine xenograft (Bo-Hy group), and HPMC-mixed porcine xenograft (Po-Hy group). At eight weeks, micro-computed tomography (µCT) scanning and histomorphometric analyses were performed to evaluate new bone formation within the defects. The results revealed that the defects treated with the Bo-Hy and the Po-Hy showed higher bone regeneration than the control group (p < 0.05), while there was no significant difference between the two xenograft groups (p > 0.05). Within the limitations of the present study, there was no difference in new bone formation between porcine and bovine xenografts with HPMC, and bone graft material was easily moldable with the desired shape during surgery. Therefore, the moldable porcine-derived xenograft with HPMC used in this study could be a promising substitute for the currently used bone grafts as it exhibits good bone regeneration ability for bony defects.

The Analysis of MMP-13 Expression on Hydroxyapatite Tooth Graft Application Compared to Hydroxyapatite Xenograft

Background: Bone graft materials are widely used to support the success of periodontal tissue treatments. Graft material has been used extensively however it has some deficiencies such as limited availability, high levels of resorption, immunological reactions and the risk of contamination as well as high costs. Therefore recent research is needed to explore potential usage of the tooth graft. Objective(s): The objective of this research is to comparing the MMP-13 expression in bone healing after grafting the incisor’s extraction sockets with hydroxyapatite tooth graft and hydroxyapatite xenograft. Research Methods: 33 adult male Cavia cobayas were divided into three groups: hydroxyapatite xenograft, hydroxyapatite tooth graft, and control (without treatment). Bone tissue sections were stained with diaminobenzidine and then dripping with anti-MMP-13 monoclonal antibody. The number of MMP-13 expression by osteoblast cells was carried out quantitatively based on the colourintensity in each group under the OLYMPUS microscope with 400x magnification. Results: The value of MMP-13 expression was higher on the tooth graft and xenograft group than the control group. The ability of osteoconduction of hydroxyapatite derived from porous hydroxyapatite structure will facilitate angiogenesis so that osteogenic cells can migrate and attach to the graft to induce the new bone growth. The tooth graft group had higher MMP-13 value than xenograft group. High solubility of graft material could affect bone remodeling and mineralization processes because of the presence of inflammatory cells is detrimental to the healing process. Conclusion: As a new graft material, tooth graft has a capability to induce osteoconductive and osteoinductive that similar with the xenograft.