athymic-rat-model-for-evaluation-engineered-anterior-cruciate

Athymic Rat Model for Evaluation of Engineered Anterior Cruciate Ligament Grafts

Anterior cruciate ligament (ACL) rupture is a common ligamentous injury that often requires surgery because the ACL does not heal well without ...

University of California Los Angeles

One of the design goals of the ideal tissue-engineered bone graft is ostoinductivity, the ability to induce the osteogenic differentiation of mesenchymal stem cells and progenitor cells. In this study, we evaluated the osteoinductive potential of a polymer-ceramic composite in vitro. This composite has been shown to be biodegradable, osteoconductive, and osteointegrative in previous studies. It is hypothesized that this composite will enhance osteoblastic differentiation in human mesenchymal stem cells (hMSCs), and that this inductive potential is substrate-dependent. Human MSCs were cultured on PLGA-BG composite scaffolds and their growth and differentiation were assessed over a four-week period. Composite scaffolds of PLGA and hydroxyapatite (HA), and hMSC cultures treated with osteogenic medium served as controls. It was found that hMSCs grown on PLGA-BG composite scaffolds expressed osteogenic markers without osteogenic media stimulation. In addition, alkaline phosphatase (ALP) activity peaked significantly earlier on the PLGA-BG composite compared to that on the PLGA scaffolds. The findings of this study collectively demonstrate the osteoinductivity of the PLGA-BG composite and its potential as a bone tissue engineering scaffold.

Polymer-ceramic composite scaffold induces osteogenic differentiation of human mesenchymal stem cells.

The decision whether to treat benign skeletal lesions surgically can be difficult to make. The purpose of this study was to validate our previously published method of predicting fracture risk with use of quantitative computed tomography-based structural analysis.

Computed tomography-based structural analysis for predicting fracture risk in children with benign skeletal neoplasms: comparison of specificity with that of plain radiographs.

Malunion is the most common complication of distal radius fracture. It has previously been demonstrated that there is a correlation between the quality of anatomical correction and overall wrist function. However, surgical correction can be difficult because of the often complex anatomy associated with this condition. Computer assisted surgical planning, combined with patient-specific surgical guides, has the potential to improve pre-operative understanding of patient anatomy as well as intra-operative accuracy. For patients with malunion of the distal radius fracture, this technology could significantly improve clinical outcomes that largely depend on the quality of restoration of normal anatomy. Therefore, the objective of this study is to compare patient outcomes after corrective osteotomy for distal radius malunion with and without preoperative computer-assisted planning and peri-operative patient-specific surgical guides.

Computer-assisted versus non-computer-assisted preoperative planning of corrective osteotomy for extra-articular distal radius malunions: a randomized controlled trial.

Rupture of the anterior cruciate ligament (ACL) is one of the most common ligamentous injuries of the knee. Limitations of allografts and autografts in ACL reconstruction as well as recent advancements in biology and materials science have spurred interest in developing tissue-engineered ACL replacements that have the potential to mimic the native ACL in terms of both biological and mechanical properties. This article reviews the current literature regarding contemporary tissue engineering strategies. The four basic components of tissue engineering, biomaterial scaffolds, cell sources, growth factors, and mechanical stimuli, as applied to the development of tissue-engineered ACL replacement grafts, will be systematically addressed. In addition, animal models that have been used to test these tissue-engineered ACL replacements will also be reviewed. To date, there is no tissue-engineered ACL construct that has been successfully implanted in humans. We expect that continued progress in designing a viable tissue-engineered ACL replacement will accompany rapidly advancing techniques in materials science and biology.

Current tissue engineering strategies in anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) rupture is a common injury often necessitating surgical treatment with graft reconstruction. Due to limitations associated with current graft options, there is interest in a tissue-engineered substitute for use in ACL regeneration. While they represent an important step in translation to clinical practice, relatively few in vivo studies have been performed to evaluate tissue-engineered ACL grafts. In the present study, we immobilized heparin onto electrospun polycaprolactone scaffolds as a means of incorporating basic fibroblast growth factor (bFGF) onto the scaffold. In vitro, we demonstrated that human foreskin fibroblasts (HFFs) cultured on bFGF-coated scaffolds had significantly greater cell proliferation. In vivo, we implanted electrospun polycaprolactone grafts with and without bFGF into athymic rat knees. We analyzed the regenerated ACL using histological methods up to 16 weeks post-implantation. Hematoxylin and eosin staining demonstrated infiltration of the grafts with cells, and picrosirius red staining demonstrated aligned collagen fibers. At 16 weeks postop, mechanical testing of the grafts demonstrated that the grafts had approximately 30% the maximum load to failure of the native ACL. However, there were no significant differences observed between the graft groups with or without heparin-immobilized bFGF. While this study demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture, it also demonstrates that in vitro results do not always predict what will occur in vivo.

In vitro and in vivo evaluation of heparin mediated growth factor release from tissue-engineered constructs for anterior cruciate ligament reconstruction.

Article	Year
Polymer-ceramic composite scaffold induces osteogenic differentiation of human mesenchymal stem cells. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference\| PubMed ID: 17946970	2006
Computed tomography-based structural analysis for predicting fracture risk in children with benign skeletal neoplasms: comparison of specificity with that of plain radiographs. The Journal of bone and joint surgery. American volume\| PubMed ID: 20686056	2010
Computer-assisted versus non-computer-assisted preoperative planning of corrective osteotomy for extra-articular distal radius malunions: a randomized controlled trial. BMC musculoskeletal disorders\| PubMed ID: 21156074	2010
Current tissue engineering strategies in anterior cruciate ligament reconstruction. Journal of biomedical materials research. Part A\| PubMed ID: 23737190	2014
In vitro and in vivo evaluation of heparin mediated growth factor release from tissue-engineered constructs for anterior cruciate ligament reconstruction. Journal of orthopaedic research : official publication of the Orthopaedic Research Society\| PubMed ID: 25363620	2015

Natalie L. Leong

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