Fiber-based tissue-enginered scaffold for ligament replacement: design consideration and in vitro evaluation

I am going to title each of the posts by the title of the article to make it easier for me to find notes on each article. P.S. the link for this article is posted in an older post.

Abstract

• ACL- "most commonly injured ligament of the knee"
• "150,000 ACL surgeries performed annually in the US"
• "biodegradable, tissue-engineered ACL graft"
• "construct architecture, porosity, degradability, and cell source"
• "polymeric fibers of polyactide-co-glycolide 10:90"
• "three-dimensional braiding technology"

Introduction

• "over 250,000 patients each year diagnosed with a torn ACL"
• "current treatment... bone-patellar, tendon-bone and hamstring-tendon"
• "donor site related problems"
• "commercially available synthetic ACL grafts... Gore Tex prosthesis, the Stryker-Dacron ligament, and the Kennedy ligament augmentation device (LAD)... long-term clinical
• Def. tissue eng.- "Tissue engineering may be defined as the application of biological, chemical, and engineering principles toward the repair, restoration, or regeneration of living tissues using biomaterials, cells, and factors alone or in combination"
• Ideal- "The ideal ACL replacement scaffold should be
  biodegradable, porous, biocompatible, exhibit sufficient
  mechanical strength, and able to promote the formation
  of ligamentous tissue."
• Architecture
• "Scaffolds developed within these
  pore size ranges will encourage tissue ingrowth, capillary
  supply, and improve the quality of anchorage in bone
  tunnels."
• "increases the overall surface area
  for cell attachment, which in turn can enhance the
  regenerative properties"
• Biodegradable materials
• no foreign body reaction
• PLGA fibers
• ACL- 3 areas where fibers arranged- "anteromedial, posterolateral,
  and intermedial"
• Objective-"design a scaffold
  that would provide the newly regenerating tissue a
  temporary site for cell attachment, proliferation, and
  mechanical stability."
• Cell source and response
• scaffold biocompatibility

Materials and Methods

• braiding, PLAGA 10:90
• Architecture- pore diameter, porosity, surface area
• Mechanical properties
• tensile strength
• load as a function of braiding angle
• cells and cell culture
• scaffold in vitro evaluation
• cell growth
• scanning electron microscopy
• "effects of braiding geometry ib the linear density, mode pore diameter, median pore
  diameter, surface area, braiding angle, and porosity of
  the scaffolds can be derived from Table 1."
• surface area
• braiding angle
• mechanical properties
• "differ in strength due to differences in strain rate
  and geometry"
• "cell adhesion and spreading on the braided scaffold"
• primary rabbit ACL cells
• "primary ACL cells clustered and grew in small groups
  on the 3-D scaffold"
• spread across fiber- Fig. 4
• cell migration and attachment- Fig. 5
• mouse 8 days- Fig. 6
• rabbit 8 days- Fig. 7
• Advantages- "controlled porosity
  and pore diameter to encourage tissue infiltration
  throughout the scaffold, which are lacking in most
  ACL artificial implants. The 3-D braiding system
  allowed for custom production of scaffolds with
  mechanical properties similar to those of natural
  ACL tissue in order to overcome issues of stress
  shielding during tissue ingrowth. In addition, the
  intertwining of the fibers within the 3-D braid prevents
  total catastrophic failure of the scaffold due to a small
  rupture."
• manipulate braiding angle to inc. or dec. porosity and mode pore diameter
• optimal pore size
• "lower limit pore size of 100 mm
  [24,25]. A minimum pore size of 150 mm has been
  suggested in the literature for bone and 200–250 mm
  for soft tissue"
• "optimal pore diameters of
  100–300 mm needed for in vivo tissue ingrowth"
• PREVIOUSLY IN PAST- "Previous ligament prostheses have been made of
  flexible composites consisting of fibers that have been
  woven or braided into structures [11,14]. These scaffolds
  performed well for a short period after implantation,
  while the long-term results have been poor [11,14]. These
  composite structures were limited by poor tissue
  integration, poor abrasion resistance, and fatigue failure
  [11,14]."
• regnerate tissue between pores
• structural properties
• "ultimate tensile strengths ranged
  fromB100 to 400 MPa"
• circular better- "the circular
  braid geometry showed a significant increase in maximum
  tensile load. The 3-D circular fibrous scaffold was
  able to withstand tensile loads of 907N (SD7132 N),
  which was greater than the level for normal human
  physical activity that is estimated to range between 67
  and 700N [40–42]."
• crimp geometry- "mimic stiffness of natural ligament"
• pore diameters- "167 and 260 um... tissue ingrowth"
• "biocompatibility of scaffold"
• rabbit slower growth than mouse
• mouse not used in future studies
• WHY NEED TISSUE ENG.- "ACL tissue engineering is need because of past
  failures in ligament reconstruction using prostheses."
• "parameters that must be addressed
  to produce a biocompatible tissue-engineered ligament
  replacement"
• NIH grant