A triphasic ceramic-coated porous hydroxyapatite for tissue engineering application

Scaffolds which encourage the incorporation of a cell source for tissue engineering applications are critical determinants for clinical defects. Over the years, a number of biomaterials have emerged for cell support and growth, but only a few have demonstrated clinical efficacy. We therefore investigated an in-house-developed silica-based bioactive ceramic for its ability to support and sustain the growth of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. For this, MSCs aspirated from goat bone marrow were isolated and culture expanded on a novel triphasic ceramic composite coated hydroxyapatite (HASi) scaffold comprising hydroxyapatite, tricalcium phosphate and calcium silicate. The viability of cells that harbored on and within the material was ensured through fluorescence-activated cell sorting and confocal laser scanning microscope and for their anchorage sites by scanning electron microscopy. Interestingly, over the days in culture, cell-cell interactions gradually morphed into woven cell-sheets that spanned across the surface of the HASi, forming a canopy. To conclude, we have attempted to carry out the preliminary cytocompatibility studies of this novel ceramic to establish its appropriateness for bone tissue engineering application which is an important criterion in orthopaedic transplantation and regenerative surgery.     

Preoperative chemoradiotherapy in locally advanced rectal cancer: correlation of a gene expression-based response signature with recurrence

Preoperative chemoradiotherapy is recommended for locally advanced rectal cancer (UICC stage II/III). We recently demonstrated that responsive and nonresponsive tumors showed differential expression levels of 54 genes. In this follow-up study, we investigated the relationship between this gene set and disease-free (DFS) and overall survival (OS). Pretherapeutic biopsies from 30 participants in the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group were analyzed using gene expression microarrays. Statistical analysis was performed to identify differentially expressed genes between recurrent and nonrecurrent tumors and to correlate these changes with disease recurrence and outcome. After a median follow-up of 59 months, seven of eight patients with recurrent disease was a nonresponder, and one responsive tumor recurred. Response to chemoradiotherapy was significantly correlated with an improved DFS (log rank P = 0.028), whereas OS did not differ significantly (P = 0.11). Applying a class comparison analysis, we identified 20 genes that were differentially expressed between recurrent and nonrecurrent tumors (P < 0.001). Analyzing the first two principal components of the 54 genes previously identified to predict response, we observed that this response signature correlated with an increased risk of cancer recurrence. These data suggest that the genetic basis of local response also affects the genetic basis of tumor recurrence. Genes that are indicative of nonresponse to preoperative chemoradiotherapy might also be linked to an increased risk of tumor recurrence.     

Prostate‐specific membrane antigen expression in tumor‐associated vasculature of breast cancers

Prostate‐specific membrane antigen (PSMA) has been found to be expressed in the tumor‐associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor‐associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0‐IV breast cancer were identified. Ninety‐two of these patients had primary breast cancer [invasive breast carcinoma with or without co‐existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor‐associated vascular endothelial cell PSMA immunoreactivity was semi‐quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor‐associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5–50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor‐associated vasculature was PSMA‐positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue‐associated vasculature. The 10‐year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10‐year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores of 0 and 1 were compared with 2, there was a statistically significant difference in OS (96.0% vs 79.7%, respectively, p = 0.05). Patients with a PSMA score of 2 had a significantly higher median tumor size compared with patients in the lower PSMA score groups (p = 0.04). Patients with higher nuclear grade were more likely to have a PSMA score of 2 compared with patients with lower nuclear grade (p < 0.0001). Patients with a PSMA score of 2 had a significantly higher median Ki‐67 proliferation index compared with patients in the lower PSMA score groups (p < 0.0001). Patients with estrogen receptor (ER)‐negative tumors were more likely to have a PSMA score of 2 compared with patients with ER‐positive tumors (p < 0.0001). Patients with progesterone receptor (PR)‐negative tumors were more likely to have a PSMA score of 2 compared with patients with PR‐positive tumors (p = 0.03). No significant association was observed between PSMA score group status and lymph node involvement (p = 0.95). Too little variability was present in Human epidermal growth factor receptor‐2 (Her2/neu) amplified tumors to correlate with PSMA score group status. To date, this is the first detailed assessment of PSMA expression in the tumor‐associated vasculature of primary and metastatic breast carcinomas. Further studies are needed to evaluate whether PSMA has diagnostic and/or potential therapeutic value.     

Reconstruction of goat femur segmental defects using triphasic ceramic-coated hydroxyapatite in combination with autologous cells and platelet-rich plasma

Segmental bone defects resulting from trauma or pathology represent a common and significant clinical problem. In this study, a triphasic ceramic (calcium silicate, hydroxyapatite and tricalcium phosphate)-coated hydroxyapatite (HASi) having the benefits of both HA (osteointegration, osteoconduction) and silica (degradation) was used as a bone substitute for the repair of segmental defect (2 cm) created in a goat femur model. Three experimental goat femur implant groups – (a) bare HASi, (b) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi (HASi + C) and (c) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi + platelet-rich plasma (HASi + CP) – were designed and efficacy performance in the healing of the defect was evaluated. In all the groups, the material united with host bone without any inflammation and an osseous callus formed around the implant. This reflects the osteoconductivity of HASi where the cells have migrated from the cut ends of host bone. The most observable difference between the groups appeared in the mid region of the defect. In bare HASi groups, numerous osteoblast-like cells could be seen together with a portion of material. However, in HASi + C and HASi + CP, about 60–70% of that area was occupied by woven bone, in line with material degradation. The interconnected porous nature (50–500 μm), together with the chemical composition of the HASi, facilitated the degradation of HASi, thereby opening up void spaces for cellular ingrowth and bone regeneration. The combination of HASi with cells and PRP was an added advantage that could promote the expression of many osteoinductive proteins, leading to faster bone regeneration and material degradation. Based on these results, we conclude that bare HASi can aid in bone regeneration but, with the combination of cells and PRP, the sequence of healing events are much faster in large segmental bone defects in weight-bearing areas in goats.     

Trend of severe abdominal injuries from bicycle accidents in children: a preventable condition

Aim: Bicycle riding is a common recreational and sport activity enjoyed by many children. Bicycle accidents are a common cause of abdominal injuries. We aim to establish the trend and the associated risk factor(s) of bicycle‐related abdominal injuries. Methods: A retrospective review of all children admitted following bicycle accidents to a single tertiary referral centre was carried out over an approximately 5‐year period. The data were tabulated and regression analyses were carried out. Results: Over the study period, 196 children were admitted into the Emergency Department. Abdominal injuries (16%) were the third largest group after orthopaedic and head injuries. There were 19 major visceral injuries, seven of whom underwent major surgeries. Forty‐two percent (8/19) of these major injuries were related to stunts. Over the same period, no child with head injury required any surgical intervention. In addition, there was a definite trend that abdominal injuries were accounting for greater percentage of bicycle‐related injuries in children. Conclusions: Severe intra‐abdominal trauma following bicycle injuries appears to be seen more often in adolescent males, especially when related to BMX stunts. These injuries have surpassed head injuries as the prime cause of morbidity from bicycle accidents. These injuries are largely preventable.