Regenerative Sports Medicine: Past, Present, and Future (Adapted From the PASSOR Legacy Award Presentation; AAPMR; October 2016).

Regenerative medicine has shown dramatic expanse and evolution in the past decade. Within that milieu, physiatrists are taking an active role in research, clinical care delivery, and education. The purpose of this review is to provide a balance among evidence, theory, experience, clinical trends, and the foreseeable future. We focus on the literature that reports the research with the best methodology in each practice area, recognizing that the level of evidence varies substantially among different treatment modalities and conditions. The following elements are included: an overview of the evolution of currently available regenerative techniques, evidence base for each available modality (prolotherapy, platelet rich plasma, bone marrow aspirate concentrate and stem cells, adipose-derived stem cells, and amniotic tissue products), general principles in the application of these treatments, and discussion and a vision of what lies ahead. We expect that practitioners will use this review to facilitate clinical decision making and to provide a core knowledge base to assist when counseling patients. LEVEL OF EVIDENCE: IV.

Fabrication of capillary-like structures with Pluronic F127® and Kerria lacca resin (shellac) in biocompatible tissue-engineered constructs.

The fabrication of large cellular tissue-engineered constructs is currently limited by an inability to manufacture internal vasculature that can be anastomosed to the host circulatory system. Creation of synthetic tissues with microvascular networks that adequately mimic the size and density of in vivo capillaries remains one of the foremost challenges within tissue engineering, as cells must reside within 200-300 µm of vasculature for long-term survival. In our previous work, we used a sacrificial microfibre technique whereby Pluronic® F127 fibres were embedded and then sacrificed within a collagen matrix, leaving behind a patent channel, which was subsequently seeded with endothelial and smooth muscle cells, forming a neointima and neomedia. We now have extended our technique and describe two approaches to synthesize a biocompatible tissue-engineered construct with macro-inlet and -outlet vessels, bridged by a dense network of cellularized microvessels, recapitulating the hierarchical organization of an arteriole, venule and capillary bed, respectively. Copyright © 2016 John Wiley & Sons, Ltd.

A Novel Three-Dimensional Platform to Investigate Neoangiogenesis, Transendothelial Migration, and Metastasis of MDAMB-231 Breast Cancer Cells.

BACKGROUND: A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation. METHODS: Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture-seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated. RESULTS: After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture-seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel "neovessel." In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture-seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively). CONCLUSION: The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena.