This thesis examined the development of a tissue-engineered ligament (TEL) for anterior cruciate ligament (ACL) repair and replacement. There was an in vitro evaluation of the cellular response to the TEL and an in vivo evaluation of the optimized TEL as an ACL replacement. Scaffold fabrication was based upon the use of poly ([Greek small letter alpha]-hydroxyester) acid fibers arranged in a 3-dimensional (3-D) braided structure. In vitro cellular evaluation of the poly(lactide-co-glycolide) (PLAGA 10:90) 3-D braided scaffold using primary rabbit ACL cells and BALB/C mouse fibroblast cell line confirmed that the scaffold was conducive to cellular attachment and proliferation. In order to select the scaffold material, a degradation study was performed on yarns of poly(L-lactide) (PLLA), poly(lactide-co-glycolide) (PLAGA 82:18) d poly(glycolide) (PGA). This study indicated that the PLLA possessed the best degradation profile for our ligament replacement design. Therefore, the homopolymer PLLA (Mw = 250,000) was chosen for its properties as the optimal material for the TEL replacement. Optimization of the PLLA 3-D braided scaffold showed relationships of scaffold size and braiding angle on properties. Mechanical optimization and adaptation for a rabbit model resulted in a PLLA 3-D braided structure with a maximum tensile load of 332 ± 20 N (strain rate = 2 %/sec). This scaffold possessed a pore system optimal for ligament regeneration (150-300 [Greek small letter mu]m). In vitro cellular evaluation studies were conducted using primary rabbit anterior cruciate ligament, medial collateral ligament, patellar tendon and Achilles tendon cells. The results indicated that the PLLA 3-D braided scaffold promoted attachment and proliferation for all cell types. The PLLA 3-D braided scaffold was evaluated in an in vivo anterior cruciate ligament reconstruction model in rabbits. The average maximum tensile load for the rabbit ACL was 314 ± 68 N. For this investigation, seeded tissue-engineered ligament (TELS) and tissue-engineered ligament (TEL) replacements were implanted into New Zealand White Rabbits. The samples were retrieved 4 weeks and 12 weeks postoperation, and characterized by mechanical and histological evaluation. The in vivo study showed an improvement in scaffold properties over implantation time using the seeded tissue-engineered ligament (TELS) replacement.
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Title
Design, optimization and in vivo evaluation of a tissue-engineered anterior cruciate ligament replacement
Creators
James Arthur Cooper - DU
Contributors
Cato T. Laurencin (Advisor) - Drexel University (1970-)
Awarding Institution
Drexel University
Degree Awarded
Doctor of Philosophy (Ph.D.)
Publisher
Drexel University; Philadelphia, Pennsylvania
Resource Type
Dissertation
Language
English
Academic Unit
School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University