Osteochondral Tissue Removal and Modification Techniques to Enhance Graft Performance
Available for Licensing
US Utility Patent Pending: US 2017/0258962 A1
Suzanne M Tabbaa
Robert L Sah
David D Frisbie
William D Bugbee
C Wayne Mcllwraith
At A Glance
Researchers at Colorado State University in collaboration with the University of California (UCSD) have developed techniques and procedures to enhance the performance of osteochondral allografts through the utilization of an enzymatic process to remove residual compositions that typically impede cell repopulation and osteochondral repair.
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Bone and cartilage injuries are highly prevalent and persistent problems in orthopedics. When left untreated, these injuries may contribute to joint irritation and inflammation over time. To repair bone and cartilage injuries, a surgeon may elect to harvest bone or cartilage tissue from the affected patient or from another donor source. The harvested tissue is processed into a graft that can be implanted into the damaged area.
In recent years, improvements to the procurement and storage processes of grafts have led to their increased use to treat bone and cartilage injuries. Although the clinical success rate for such procedures is generally high, later complications that may occur are associated with inadequate bone integration and formation at the graft site. Furthermore, as demand for graft implantation to treat bone and cartilage injuries increases, the availability of donor grafts is limited due to sub-optimal storage conditions.
Currently procedures for processing donor grafts are limited by poor preservation of the functional properties of the graft, creating an opportunity to improve graft processing techniques and graft compositions.
Failures of osteochondral allograft transplantation are associated with increased immunogenic response, slow bone formation and integration, and lack of mechanical stability. This technology specifically addresses the problem of residual adipose bone marrow housed within the trabeculae of osteochondral allografts that may impede the attachment and repopulation of host cells, leading to slow bone formation and integration. The standard procedure to remove bone marrow involves gentle agitation with centrifugation and sonication to avoid damage to the chondrocytes. Pulse lavage with saline is also used to remove residual marrow intra-operatively during graft preparation. Here, researchers have developed (1) a process to remove residual adipose marrow and improve cell repopulation and (2) a product, an osteochondral allograft depleted of adipose marrow elements.
The rationale for the cleansing process is based on the components of adipose marrow elements, which are comprised primarily of lipids and triglycerides. The process defined here removes lipids and triglycerides from the bone component of osteochondral allografts by using lipase, a naturally occurring enzyme with activity to drive the breakdown of lipids through the hydrolysis of triglycerides into glycerol and fatty acids. Lipases are well established in commercial biotechnology industries including the food, detergent, and pharmaceutica lindustry. This process uses various lipase types and combinations to remove adipose bone marrow without adversely affecting the cartilage and changing the structural and functional properties of the bone component.
Following lipase treatment, osteochondral allografts can be stored and distributed following FDA standards and regulations. The product produced by this process is an osteochondral graft depleted of residual adipose marrow with or without bone channels that can be used in combination with autologous cells intra-operatively prior to implanting in the defect site. The marrow depleted osteochondral graft with and without channels will improve initial cell infiltration of autologous cells prior to implantation.
Figure 1: A (left) – microCT and gross cross-sectional images; B (right) – Oil Red O sections and LIVE/DEAD
Figure 1 (A) microCT and digital gross images. (1a-c) Lavage cleansed OC core (1a) Transverse microCT image (1b) Coronal microCT image (1c) gross image. (2a-c) Lipase cleansed OC core (2a) Transverse microCT image (2b) CoronalmicroCT image
Figure 1 (B) Histology analysis with ORO and LIVE/DEAD (1a-b) Non-cleansed OC core (1a) ORO of non-cleansed core show intact bone marrow (1b) Chondrocyte viability, labeled green, of the non-cleansed control group (2a-b) Lipase cleansed OC core (2a) ORO staining shows lipase breaks down adipose bone marrow tissue (2b) Chondrocyte viability, labeled green, similar to the control group
- Avoids physical Agitation and chemical detergents (which cause cell death and damage the functional and structural properties of the tissue)
- Uses non-toxic aqueous solutions
- Preliminary data indicate the procedure can improve outcomes of large chondral lesions by enhancing bone integration and osteochondral repair
Bone grafts for a spectrum of orthopaedic procedures:
- Spinal fusion
- Trauma fixation
- Joint reconstruction
- Carniomaxillofacial procedures
ORS 2017 Annual Meeting Poster No. 0411: The Effect of Warming on Release of Marrow Elemnts from Osteochondral Cores
Sun, Yang, et al. “Pulsed Lavage Cleansing of Osteochondral Grafts Depends on Lavage Duration, Flow Intensity, and Graft Storage Condition.” PLOS ONE, Public Library of Science, 2017, journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0176934.
Last updated: May 2020