Frontiers in Bioscience 1. http://en.wikipedia.org/wiki/Anterior_cruciate_ligament Wikipedia says articular ligaments are most commonly referred to. http://medicalcenter.osu.edu/PATIENTCARE/healthcare_services/orthopaedics/joint/ligament_injuries_ to_knee/Pages/index.

aspx This site explains that the ACL (Anterior Cruciate Ligament) is one of most common ligaments to be injured http://medicalcenter.osu.edu/greystone/images/ei_0277.gif Picture of left knee from behind - anatomy http://en.wikipedia.org/wiki/Anterior_cruciate_ligament_reconstruction Gives the procedure for replacing an Anterior Cruciate ligament. Mentions two types of graft: Allograft From Donor Autograft - From patients body http://www.coe.pku.edu.cn/tpic/201072115415651.pdf Says the Mesoenchymal stem cells are a better source of cells than ACL and MCL fibroblasts. http://wings.buffalo.edu/academic/department/eng/mae/courses/417517/Orthopaedic%20Biomechanics/Lecture%203u.pdf Combined with the slide on ligaments from the lecture, this link confirms the cells in ligaments are fibroblasts. Composition of ligament from page 6 is: to be discussed tomorrow

http://books.google.co.uk/books?id=A40OI8cfasYC&pg=PA521&lpg=PA521&dq=%22Anterior+cruciate+l igament+constructs+fabricated+from+human+mesenchymal+stem+cells+in+a+collagen+type+I+hydroge l%22&source=bl&ots=oC5B4KCcZq&sig=O4zKZXeysdTFSNhfnLRtA1Fa2M8&hl=en&sa=X&ei=JMSMUuXrJ vCZ0QXuk4GYAQ&ved=0CDYQ6AEwAg#v=onepage&q=Anterior%20cruciate%20ligament%20constructs %20fabricated%20from%20human%20mesenchymal%20stem%20cells&f=false P505 MSCs produce more collagen per cell. http://www.ncbi.nlm.nih.gov/pubmed/16236634 Abstract suggests that
1. We take human MSC cells and "fabricate an ACL construct in vitro" (Batch)

2. Put them on collagen hydrogel with some kind of mineral cylinder to act as a bone, wait for a while, so they and the gel can attach to the bone. (Batch) 3. Then mechanically stretch them. (Batch cells, continuous nutrients and oxygen).

http://www.swetswise.com.ezproxye.bham.ac.uk/FullTextProxy/swproxy?url=http%3A%2F%2Fwww.lie bertonline.com%2Fdoi%2Fpdf%2F10.1089%2Ften.teb.2011.0465&ts=1384961187751&cs=3155515037 &userName=8080910.ipdirect&emCondId=1244868&articleID=166735094&yevoID=99036740&titleID= 509279&remoteAddr=147.188.128.74&hostType=PRO 2D and 3D mech stretching This source states that at less than 1 Hz of load the cells align parallel to the direction of load. At 1 Hz or more they arrange themselves perpendicular to maintain stress/strain homeostasis. So to limit strain on the system. http://pre.aps.org.ezproxyd.bham.ac.uk/pdf/PRE/v80/i6/e060901 Is meant to back this up. http://www.ncbi.nlm.nih.gov/pubmed/16236634 Abstract says cyclic stretching at 1 Hz was applied for 2 weeks, 8 hours a day. So does cell reproduction happen in the MSC phase or the fibro blast phase? http://stemcells.nih.gov/info/basics/pages/basics2.aspx This source says that stem cells can divide and renew themselves over a long time. http://elib.fk.uwks.ac.id/asset/archieve/e-book/BEDAH%20%20SURGERY/Walsh_Repair%20and%20Regeneration%20of%20Ligaments%20Tendons%20and%20Join t%20Capsule.pdf Page 281 states repair and regeneration are two separate things. Regeneration mimics embryonic development. For most soft tissues, there is a race between repair and regeneration. The fibrotic repair response results in scar tissue that is not as satisfactory as the original.

How do the MSC cells differentiate into fibro-blasts? How many cells do we need to start with? Work backwards from how many needed to produce. What nutrients are needed for each type of cells?