Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now known that these peptides also regulate non-neuronal tissues, including bone. Here, we review the effects of numerous neuropeptides and neurotrophins on fracture healing. The neuropeptides calcitonin-gene related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) have varying effects on osteoclastic and osteoblastic activity. Ultimately, CGRP and SP both accelerate fracture healing, while VIP and PACAP seem to negatively impact healing. Unlike the aforementioned neuropeptides, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have more uniform effects. Both factors upregulate osteoblastic activity, osteoclastic activity, and, in vivo, stimulate osteogenesis to promote fracture healing. Future research will need to clarify the exact mechanism by which the neuropeptides and neurotrophins influence fracture healing. Specifically, understanding the optimal expression patterns for these proteins in the fracture healing process may lead to therapies that can maximize their bone-healing capabilities and minimize their painpromoting effects. Finally, further examination of protein-sequestering antibodies and/or small *

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Two complete unicondylar surface replacement scaffold designs to support tissue-engineered cartilage growth that utilized adult endogenous stem cells were 3D printed and tested in a dog stifle model. Integrated rosette strain gauges were calibrated and used to determine shear loading within stifle joints for up to 12 months. An activity index that compared extent of daily activity with tissue formation showed differences in the extent and quality of new tissue with the most active animal having the most new tissue formation. Shear loads were highest early and decreased with time indicating that cartilage tissue formation begins while tissues experience high shear loads and continues as the loads decrease toward normal physiological levels. Scaffolds with biomimetic support pegs facilitated the most rapid bone ingrowth and were noted to have more cartilage formation with better quality cartilage as measured using both indentation testing and histology. Comparison of implant placement depth to previous studies suggested that placement depth affects the amount of tissue formation. This study provides measurements of loading patterns and cartilage regeneration on a complete medial condylar surface replacement that can be used for preclinical testing of a tissue engineering approach for the most common form of early stage osteoarthritis, unicondylar disease. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1409-1421, 2017.

Background and Hypothesis: Injury to soft tissue with volumetric muscle loss (VML) concomitant to segmental bone defects (SBDs) can be difficult to treat. One potential option is skeletal muscle autograft (SMA). We hypothesize the maximal torque measured in vivo and Radiographic Union Scale for Tibial Fractures (RUST) scores will be increased in the VML+SBD+SMA group compared to the VML+SBD group, but will be decreased compared to SBD alone. Experimental Design or Project Methods: 18 male, Yucatan minipigs aged 1821 months were randomized into 3 groups: VML+SBD+SMA, VML+SBD, and SBD. This study is still ongoing with 12 pigs having had the surgery performed to date. In vivo muscle testing was performed prior to surgery in both hindlimbs to assess baseline strength. RUST scores and in vivo muscle testing was/will be performed at 1, 2, and 3 months post-injury. All procedures were conducted following approved IACUC protocol. Results: Muscle testing results demonstrate no significant difference between control and operative limbs pre-surgery (T-tests, p= 0.673, 0.824, and 0.739 for VML+SBD+SMA, VML+SBD and SBD groups, respectively), or between the 3 different groups pre- or post-surgery (2-way ANOVA, p=0.788). The average RUST score for each treatment group at 2 months was 6.8±2.2, 7.7 7.7±1.1, and 8.6 8.6±0.4 for VML+SBD+SMA (n=2), VML+SBD (n=5), and SBD (n=3) groups, respectively. Conclusion and Potential Impact: The lack of difference amongst groups on pre-operative muscle testing and a difference post-operatively between control and operative legs post-operatively help to validate this study. Preliminary results demonstrate a reduced RUST score for the VML+SBD+SMA group; however, this along with the lack of difference found in muscle testing results postoperatively may be an artifact due to small sample size and/or timing. Development of a model for VML and SBD will allow for testing of therapies for treat clinical problems.