Pascual-Garrido Projects

Experimental approaches to improve articular cartilage repair have increasingly focused on regenerative medicine techniques with particular emphasis on adult stem cell-based therapies. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are among the most widely studied stem cells. Favorable outcomes have been reported with human MSCs for in vitro chondrogenesis and joint repair in animal models; however, engraftment and regeneration of articular cartilage in human patients has not been convincingly demonstrated. To be able to efficiently deliver stem cells, a scaffold should be used. This scaffold (matrix) can influence stem cell behavior regarding self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation or apoptosis. Also, this scaffold could be printed in specific 3-D constructs using specific bioprinters. Lately, a biomaterial has been developed that is capable of resembling the native cartilage biomechanical properties, in which stem cells can be seeded and differentiate while the hydrogel degrades. The central hypothesis of the proposal is that PEG/ChS hydrogel seeded with MSCs will enhance cartilage repair.

The objective of the study is to evaluate the performance of biologically assisted core decompression performed with the PerFuse instrument and BioCUE in patients with bone lesion(s) of the femoral head. The study will explore the potential impact of patient demographics and baseline characteristics on post-operative outcomes. In addition, the utilization of healthcare resources and associated costs will be investigated in treated patients.

The objective of this project is to investigate the metabolic activity in the pre-OA hip joint (FAI and DDH). The results of this study may be the first step toward better understanding of the pathological pathway(s) of hip joint degeneration, which could lead in the long term to development of novel and improved therapies to delay or prevent the development of OA.

The mechanism of progression to joint cartilage degeneration in DDH hips is undefined. The dog that has canine hip dysplasia (CDH) is an attractive natural animal model to investigate DDH. The objective of this project is to characterize, prospectively, hip cartilage wear, cartilage degeneration and metabolic activities in hip cartilage samples at 6, 10-12 months old in CHD.

FAI is considered to be one of the main causes of early OA in young-adult patients. A mechanical concept has been proposed, suggesting that the repeated mechanical impingement of the femoral head-neck junction area into the acetabular rim results in chronic inflammation in the head-neck cartilage. The objective of this project is to investigate if severity of Cam deformity, assessed by the alpha angle, correlates with severity of cartilage degeneration in patients with symptomatic hip Cam FAI.

Acetabular cartilage wear is a common finding in young-adult patients undergoing surgical treatment for symptomatic FAI. Inflammation is considered to be one of the main initiators of joint OA. The objective of this project is to investigate the histological changes and expression of inflammatory and OA markers in acetabular cartilage lesions in patients undergoing surgery for the treatment of symptomatic FAI.

Intraarticular inflammation plays a critical role in the development of OA and has been observed in cartilage from impingement zone in patients with symptomatic FAI. Synovial inflammation is a common and important feature of hip OA. The objective of this project is to assess for microscopic synovitis and inflammatory molecules in synovium and cartilage from femoral head-neck in patients with symptomatic early and late stage FAI.

It has been shown that concomitant osteochondroplasy in patients undergoing a PAO is associated with decreased risk of failure, suggesting removal of concomitant impingement improves joint homeostasis. The object of this project is to analyze tissue morphology and early osteoarthritic changes in cartilage samples obtained from the head-neck impingement area in patients with symptomatic DDH that underwent PAO.

We are proposing an animal model of hip deformity by injuring the cartilage epiphysis of the femoral head. It has been well established that epiphysis arrest of the proximal head results in hip deformity. Since the anatomy of the hip joint in rabbit is similar to that of human and the hip size of the rabbit is optimal to perform adequate surgical intervention and assess respond to treatment, rabbits are appropriate as an animal model for the hip. The objective of this project is to develop and characterize an animal model of hip FAI.

We want to explore the 3-D variation seen in osteonecrotic lesions using statistical shape modelling. We will explore if this model can give further insight into the structure-function relationship. In addition, the modeled structure can be used to guide the synthesis of anatomically-shaped tissue for joint resurfacing and lesion repair.

The goal is to determine the incidence of pain in the contralateral hip of DDH patients at 5 years and to determine the factors associated with the development of hip pain.

FAI and DDH are considered to be the main causes of hip OA. However, the mechanisms for progressing the hip joint to OA differ between FAI and DDH. mRNA was isolated from femoral head-neck cartilage from patients with early FAI, late FAI, early DDH or late DDH. The objective of this project is to investigate the differences in gene expressions and biological processes among groups by RNA-seq. The goal is to identify the specific genes related to the progression of the hip OA with FAI or DDH.