Bioprinting of osteochondral tissues: A perspective on current gaps and future trends.

Osteochondral tissue regeneration has remained a critical challenge in orthopaedic surgery, especially due to complications of arthritic degeneration arising out of mechanical dislocations of joints. The common gold standard of autografting has several limitations in presenting tissue engineering strategies to solve the unmet clinical need. However, due to the complexity of joint anatomy, and tissue heterogeneity at the interface, the conventional tissue engineering strategies have certain limitations. The advent of bioprinting has now provided new opportunities for osteochondral tissue engineering. Bioprinting can uniquely mimic the heterogeneous cellular composition and anisotropic extra-cellular matrix (ECM) organization, while allowing for targeted gene delivery to achieve heterotypic differentiation. In this perspective, we discuss the current advances made towards bioprinting of composite osteochondral tissues and present an account of challenges-in terms of tissue integration, long-term survival, and mechanical strength at the time of implantation-required to be addressed for effective clinical translation of bioprinted tissues. Finally, we highlight some of the future trends related to osteochondral bioprinting with the hope of in-clinical translation.

ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.

Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells. Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis. These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.

Comprehensive axillary evaluation in neoadjuvant chemotherapy patients with ultrasonography and sentinel lymph node biopsy.

BACKGROUND: There is ongoing debate regarding the optimal sequence of sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (CTX) for breast cancer. We report the accuracy of comprehensive pre-neoadjuvant CTX and post-neoadjuvant CTX axillary staging via ultrasound imaging, fine-needle aspiration (FNA) biopsy, and SLN biopsy. METHODS: From 2001 to 2004, 91 neoadjuvant CTX patients at the University of Michigan Comprehensive Cancer Center underwent axillary staging by ultrasonography, ultrasound-guided FNA biopsy, SLN biopsy, or a combination of these. RESULTS: Axillary staging was pathologically negative by pre-neoadjuvant CTX SLN biopsy in 53 cases (58%); these patients had no further axillary surgery. In 38 cases (42%), axillary metastases were confirmed at presentation by either ultrasound-guided FNA or SLN biopsy. These 38 patients underwent completion axillary lymph node dissection (ALND) after delivery of neoadjuvant CTX. Follow-up lymphatic mapping was attempted in 33 of these cases, and the SLN was identified in 32 (identification rate, 97%). One third of these cases were completely node negative on ALND. Residual metastatic disease was identified in 22 cases, and the SLN was falsely negative in 1 (4.5%). CONCLUSIONS: Patients receiving neoadjuvant CTX can have accurate axillary nodal staging by ultrasound-guided FNA or SLN biopsy. In cases of documented axillary metastasis at presentation, repeat axillary staging with SLN biopsy can document the post-neoadjuvant CTX nodal status. This strategy optimizes pre-neoadjuvant CTX and post-neoadjuvant CTX staging information by distinguishing the patients who are node negative at presentation from those who have been downstaged to node negativity and offers the potential for avoiding unnecessary ALNDs in both of these patient subsets.