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Connective Tissue Biochemistry Laboratory

The scientific research of Dr. Amiel’s laboratories focus on multiple studies:

Translational Research:

  • Procurement and storage of fresh osteochondral allografts
    • Fresh osteochondral (OC) allografting is one of the oldest and most effective surgical treatments for large chondral defects in the knee. A primary limitation of this procedure is the lack of tissue availability, which is due in part to the short acceptable storage time. Storage in lactated ringers (LR) solution, the traditional storage solution, leads to a decrease in chondrocyte viability, viable cell density, and metabolic activity of the chondrocytes over a period of time. We have demonstrated regional susceptibility to storage environments, as the most superficial zone of cartilage demonstrates a disproportionately high degree of chondrocyte death in comparison to the middle and deep zones. Based on our published data, which has become a template for orthopaedic surgeons, fresh osteochondral allografts should be implanted within 7 days of harvest if stored in LR. Prolonged permissible storage periods may be possible with alternative storage media (Williams SK et al., J Bone Joint Surg 85:2111-2120, 2003; Osteoarth Cart 11(A):S9, M22, 200; and Osteoarth Cart 11(A):S20, P53, 2003).
    • To enhance the storage of osteochondral allografts, we focused on developing a modified culture media which is now used by most tissue banks. The published results show clear evidence that there is enhancement of chondrocyte viability, viable cell density, and metabolic chondrocyte activity when stored in the above culture media in comparison with storage in LR. We have increased surgical implantation storage time to 14 days by preserving the fresh osteochondral allograft (Ball ST et al, Clin Orthop 418:246-252, 2004). The improvement of storage and procurement of these allografts has allowed total joint reconstruction surgeons to increase surgical biological joint reconstruction.
  • Clinical approach to viscosupplementation for osteoarthritis patients
    • Clinical Approach to Viscosupplementation: Intra-Articular Hyaluronan Therapy for OA: We have demonstrated the effect of hyaluronan (HA) during the development of OA, and have postulated and demonstrated the mechanism of this therapeutic compound, which is now widely used clinically as an injectable solution in patients with early OA (Amiel D et al., Osteoarth Cart 11(9):636-643, 2003; Shikhman AR et al., Osteoarth Cart 11(A):S9, M24, 2003; and Annals Rheum Dis 64:89-94, 2005). Mechanism of HA: Following injections of HA in the synovial cavity of the knee, the compound downregulates IL1, expressed by the synoviocytes, which in turn downregulates MMP-3 expressed by the chondrocytes of OA articular cartilage, slowing down ECM degradation.
    • Development of probe, i.e. radiofrequency (RF), using plasma energy for new surgical techniques
  • Using plasma energy generated by newly developed probes (i.e. radiofrequency), we have developed new surgical techniques.
    • Tasto JP, et al. (Arthroscopy 21(7):851-860-2005) describes a new procedure performed in sports medicine to treat lateral epicondylitis. He also describes (Sports Med Arthrosc Rev 12(4):210-219, 2004) new applications of radiofrequency (RF) treatment for patients developing tendonitis. Allen RT, et al. (Sports Med Arthrosc Rev 12(4):210-219, 2004) describes meniscal debridement with an arthroscopic RF wand compared to normal treatment with an arthroscopic shaver.

Basic Research:

  • Relationship between aging and osteoarthritis (OA)
    • Relationship between Aging and Osteoarthritis (OA). We have focused on genetic and molecular changes leading to specific alterations of aged articular cartilage and its propensity for developing OA. We found similarities in gene expression between the aging process and development of OA, as seen in parallel increases in gene expression of caspase 8 and Fas. The caspases are a family of serine proteases which are the effector enzymes of apoptosis, leading to DNA fragmentation and eventual cell death. Caspases are likely important to both processes, and abundant activation of caspase cascades may transform the cellular loss of aged cartilage to the frank degeneration of OA. Fas-Fas ligand interaction at the cell surface has been previously linked to OA, and can activate downstream pro-apoptotic enzymes, including caspases. MMP-1 and aggrecanase, which degrade ECM components, were increased in aged cartilage, implying a role for matrix loss in the altered properties of aged cartilage (Amiel D et al., Osteoarth & Cart 11(9):636-643, 2003; Sasho T et al., Orthop Res Soc (ORS) 28:P0619, 2003; Kobayashi K et al., Orthop Res Soc (ORS) 28:P0566, 2003; Shikhman AR et al., Osteoarth Cart 11(A):S9, M24, 2003; Allen RT et al., Osteoarth Cart 11(A):S53, P147, 2003; Coutts RD et al., Osteoarth Cart 11(A):S97, P271, 2003; Allen RT et al., Osteoarth Cart 12:917-923, 2004; Robertson CM et al., Intl Cart Repair Soc (ICRS), 476, 2004; Shikhman AR et al., Annals Rheum Dis 64:89-94, 2005; and Robertson CM et al., Orthop Res Soc (ORS) Mtng, 30:1432, 2005).
  • Tissue engineering of articular cartilage
    • Tissue engineering of articular cartilage: Our laboratories have tissue engineered construct of articular cartilage with mesenchymal stem cells, and perichondrial cells using PLA as a biodegradable scaffold. Animal models have been developed to assess the constructs in an effort to enhance cartilage regeneration (Roubin R et al., Osteo & Cart 10(A):S41, 2002; Giurea A et al., J Orthop Res 21(4):584-589, 2003; Lane JG et a., Orthop Res Soc (ORS) 28:P0720, 2003 and Am J Sports Med 32(6):1440-1450, 2004; and Ball ST et al., Clin Orthop 420:276-285, 2004).
  • Assessment of healing of flexor tendon insertion site injuries.
    • Assessment of healing of injuries at the flexor tendon insertion site (Boyer MI et al. J Hand Surg28(3):469-474, 2003; Boyer M et al. Orthop Res Soc (ORS) 28:P0835, 2003; Silva MJ et al. Orthop Res Soc (ORS), 30:0018, 2005; Thomopoulos S et al., Orthop Res Soc (ORS) Mtng, 30:1093, 2005, and J Hand Surg 30A(3):441-447, 2005).

There have been several important discoveries generated from Dr. Amiel’s laboratories which have made significant impacts in the field of orthopaedics. These discoveries include:

  • Continuous passive motion (CPM) machine, which led to use in rehabilitation following total joint replacement and soft tissue injury repair of the knee.
  • First laboratory to categorize the biochemical composition and differences between tendon and ligament, important findings in the field of arthroscopy.  "Ligamentization."  Identified the cellular function, adaptation, and explained the fate of autograft and allograft use in anterior cruciate ligament (ACL) reconstruction and meniscal transplant.  This was an important discovery for arthroscopic surgery.  Hyaluronen (HA) injections for prevention of early development of osteoarthritis (OA). Data submitted from our laboratories supported the FDA approval of Supartz® to be used clinically.Gene therapy: Compositions for receptor/liposome-mediated transfection and method of using same. Patent filed with UCSD U.S. Patent Appl No 09/248,256
  • First in the nation to report development of a radiofrequency (RF) probe to treat lateral epicondylitis.