The Color-Period Diagram and Stellar Rotational Evolution - New Rotation Period Measurements in the Open Cluster M34

We present results from a 5-month photometric survey for stellar rotation periods combined with a 4-year radial-velocity survey for membership and binarity in the 220Myr open cluster M34. We report surface rotation periods for 120 stars, 83 of which are late-type cluster members. A comparison to previous work serves to illustrate the importance of high cadence long baseline photometric observations and membership information. The new M34 periods are less biased against slow rotation and cleaned for non-members. The rotation periods of the cluster members span more than an order of magnitude from 0.5 day up to 11.5 days, and trace two distinct rotational sequences - fast (C) and moderate-to-slow (I) - in the color-period diagram. The sequences represent two different states in the rotational evolution of the late-type cluster members. We use the color-period diagrams for M34 and for younger and older clusters to estimate the timescale for the transition from the C to the I sequence and find ~<150Myr, ~150-300Myr, and ~300-600Myr for G, early-mid K, and late K dwarfs, respectively. The small number of stars in the gap between C and I suggest a quick transition. We estimate a lower limit on the maximum spin-down rate (dP/dt) during this transition to be ~0.06 days/Myr and ~0.08 days/Myr for early and late K dwarfs, respectively. We compare the I sequence rotation periods in M34 and the Hyades for G and K dwarfs and find that K dwarfs spin down slower than the Skumanich rate. We determine a gyrochronology age of 240Myr for M34. We measure the effect of cluster age uncertainties on the gyrochronology age for M34 and find the resulting error to be consistent with the error estimate for the technique. We use the M34 I sequence to redetermine the coefficients in the expression for rotational dependence on color used in gyrochronology (abridged).Comment: 47 pages (12pt, preprint), 14 figures, 2 tables, Accepted for publication in ApJ, format of RA coordinates in Table 2 corrected in latest versio

Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro

Focal cartilage defects caused by joint injury have a limited capacity to self-repair and, if left untreated, can lead to the early onset of osteoarthritis. The current standard of care, microfracture surgery, induces an endogenous repair response, but typically results in poorly integrated fibrocartilage, rather than native hyaline cartilage. The objective of this study was to test the hypothesis that a self-assembling peptide hydrogel functionalized with the proanabolic growth factor heparin-binding insulin-like growth factor-1 (HB-IGF-1) may improve integration between native cartilage and neotissue when combined with a brief enzymatic pretreatment to the defect site. This enzymatic pretreatment releases proteoglycans from the walls of the surrounding native cartilage in a controlled manner and, thereby, creates space for newly synthesized repair tissue to anchor and integrate with adjacent host cartilage. We used an in vitro model in which a cylindrical annulus of native cartilage was pretreated with trypsin over a 2-min period and then filled with a chondrocyte-seeded [KLDL]3 hydrogel functionalized with proanabolic HB-IGF-1 that had been premixed into the gel. This procedure was deemed to be clinically tractable in the context of ongoing parallel animal studies as a method to augment the microfracture procedure. The trypsin pretreatment depleted proteoglycan content of adjacent cartilage in a controlled manner without inducing cell death. The addition of HB-IGF-1 was found to stimulate matrix biosynthesis both in the surrounding cartilage and the chondrocyte-seeded KLD scaffold, and to enhance mechanical integration of neotissue into native matrix. A critical attribute for the long-term success of cartilage defect repair is the strong integration between the repair tissue and the surrounding native tissue. Current approaches utilized by physicians fail to achieve this attribute, leading to eventual relapse of the defect. This article demonstrates the concept of a simple, clinically viable approach for enhancing tissue integration via the combination of a safe, transient enzymatic treatment with a locally delivered, retained growth factor through an in vitro hydrogel/cartilage explant model.National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR060331

Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels

Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind specifically to cartilage and to promote sustained upregulation of proteoglycan synthesis in cartilage explants. Achieving strong integration between native cartilage and tissue-engineered cartilage remains challenging. We hypothesize that if a growth factor delivered by the tissue engineering scaffold could stimulate enhanced matrix synthesis by both the cells within the scaffold and the adjacent native cartilage, integration could be enhanced. In this work, we investigated methods for adsorbing HB-IGF-1 to self-assembling peptide hydrogels to deliver the growth factor to encapsulated chondrocytes and cartilage explants cultured with growth factor-loaded hydrogels. We tested multiple methods for adsorbing HB-IGF-1 in self-assembling peptide hydrogels, including adsorption prior to peptide assembly, following peptide assembly, and with/without heparan sulfate (HS, a potential linker between peptide molecules and HB-IGF-1). We found that HB-IGF-1 and HS were retained in the peptide for all tested conditions. A subset of these conditions was then studied for their ability to stimulate increased matrix production by gel-encapsulated chondrocytes and by chondrocytes within adjacent native cartilage. Adsorbing HB-IGF-1 or IGF-1 prior to peptide assembly was found to stimulate increased sulfated glycosaminoglycan per DNA and hydroxyproline content of chondrocyte-seeded hydrogels compared with basal controls at day 10. Cartilage explants cultured adjacent to functionalized hydrogels had increased proteoglycan synthesis at day 10 when HB-IGF-1 was adsorbed, but not IGF-1. We conclude that delivery of HB-IGF-1 to focal defects in cartilage using self-assembling peptide hydrogels is a promising technique that could aid cartilage repair via enhanced matrix production and integration with native tissue.Stem Cell and Regenerative Biolog