Strategy for Tissue Engineering of Osteochondral Constructs

Author(s):  
Erica Takai ◽  
X. Edward Guo ◽  
Helen H. Lu ◽  
Michelle A. LeRoux ◽  
Priya Raina ◽  
...  

Damage to articular cartilage is a common condition affecting the joints of millions of people. This is a major problem considering the poor regenerative capacity of adult articular cartilage and the disability and pain that accompanies these injuries [13]. There exists a range of options that have been applied in clinical practice, with variable degrees of success, for repair of focal lesions and damage of the articular surface, including tissue adhesives [1,6,11,12,18], enzymatic treatments [8] and laser solder welding [21], autograft cell/tissue transfer via osteoperiosteal grafts [17], osteochondral grafts (mosaicplasty) [10] and Carticel [4,5]. The poor healing capacity of articular cartilage [13], potential for donor site pain and morbidity in autograft procedures, risk of disease transmission in allograft procedures, and the limited longevity of arthroplasty systems (i.e., ∼15 years for a total knee arthroplasty), has generated considerable research efforts to develop cell-based therapies for articular cartilage repair and replacement.

1995 ◽  
Vol 16 (4) ◽  
pp. 187-190 ◽  
Author(s):  
Marc B. Danziger ◽  
Richard V. Abdo ◽  
J. Elliot Decker

Forty patients since 1988 have had distal tibial bone grafting for 41 arthrodeses of the foot and ankle. Bone graft is obtained through a cortical window made just above the medial metaphyseal distal tibial flare. Average follow-up was 23.3 months. Forty of 41 arthrodesis sites fused; there was only one nonunion. There were no delayed unions. There were no complications at the donor site based on patient examination and radiographs. Ipsilateral ankle motion was not affected by the bone graft procedure. Cited complications from iliac crest bone graft include donor site pain, blood loss, heterotopic bone formation, pelvic instability, iliac hernia, infection, fracture, and deformity. Complications with allografts include disease transmission and immune response. These are avoided by using locally obtained distal tibia autograft for arthrodeses in the foot and ankle.


2002 ◽  
Vol 25 (5) ◽  
pp. 434-441 ◽  
Author(s):  
E. Pişkin

Biomaterials made of polymers, metals or their alloys, ceramics and their composites, are used as implants to restore or to replace the damaged soft and hard tissue/organ functions for an intended time period. Biomaterials made of synthetic materials are very simple materials compared to their natural counterparts, they only replace very simple functions of the damaged tissue during healing. Natural tissues have been used for both soft and hard repair and replacement, but they do have serious limitations such as: shortage of donor tissue, donor site morbidity, unpredictable resorption characteristics, immunogenic response, risk of disease transmission, and ethical limitations. Tissue engineering is a relatively new approach, in which healthy mammalian cells are used with supporting matrices, usually made of either natural or synthetic polymers as composite bioartificial implants. Primary cells, especially embryonic stem cells, cell lines, hybridomas, genetically modified cells are considered as potential sources for this application. Both closed and open matrices are used as support matrices. Nondegradable and biocompatible microcapsules and hollow fibers are utilized in closed systems, especially for immunoprotection of the transplanted cells. Biodegradable polymers, both natural and synthetic are used in the preparation of bioartificial implants carrying only autogenic cells.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amr Abdel-Mordy Kandeel

Abstract Background Reconstruction of reverse Hill-Sachs defect using osteo-chondral allograft has the advantages of spherical re-contouring and provision of smooth biological articular surface of the reconstructed humeral head. However, worldwide availability and risk of disease transmission of osteo-chondral allograft remain points of increasing concerns. As an alternative to lacking osteo-chondral allograft, the current technical note describes a reconstructive technique of reverse Hill-Sachs defect using autologous fibular grafting. Methods Following open reduction of the dislocated humeral head, reverse Hill-Sachs defect was reconstructed using 3–4 autologous fibular pieces (each is of 10 mm in length) fixed in flush with the articular cartilage using 4-mm cancellous screws. Defect reconstruction was then followed by modified McLaughlin’s transfer and posterior capsulorrhaphy. Results Spherical contour of the humeral head and gleno-humeral range of motion were restored. Intra-operative dynamic testing of the reconstruct revealed no residual posterior gleno-humeral instability. Conclusion Currently reported technique might offer advantages of graft availability, technical simplicity, familiarity and reproducibility, safety (i.e. no disease transmission) and bone preservation facilitating future revision management (if needed). Nevertheless, long-term outcomes of this technique should be investigated via further cohort clinical studies.


2021 ◽  
Vol 6 (1) ◽  
pp. 247301142097570
Author(s):  
Mossub Qatu ◽  
George Borrelli ◽  
Christopher Traynor ◽  
Joseph Weistroffer ◽  
James Jastifer

Background: The intermetatarsal joint between the fourth and fifth metatarsals (4-5 IM) is important in defining fifth metatarsal fractures. The purpose of the current study was to quantify this joint in order to determine the mean cartilage area, the percentage of the articulation that is cartilage, and to give the clinician data to help understand the joint anatomy as it relates to fifth metatarsal fracture classification. Methods: Twenty cadaver 4-5 IM joints were dissected. Digital images were taken and the articular cartilage was quantified by calibrated digital imaging software. Results: For the lateral fourth proximal intermetatarsal articulation, the mean area of articulation was 188 ± 49 mm2, with 49% of the area composed of articular cartilage. The shape of the articular cartilage had 3 variations: triangular, oval, and square. A triangular variant was the most common (80%, 16 of 20 specimens). For the medial fifth proximal intermetatarsal articulation, the mean area of articulation was 143 ± 30 mm2, with 48% of the joint surface being composed of articular cartilage. The shape of the articular surface was oval or triangular. An oval variant was the most common (75%, 15 of 20 specimens). Conclusion: This study supports the notion that the 4-5 IM joint is not completely articular and has both fibrous and cartilaginous components. Clinical Relevance: The clinical significance of this study is that it quantifies the articular surface area and shape. This information may be useful in understanding fifth metatarsal fracture extension into the articular surface and to inform implant design and also help guide surgeons intraoperatively in order to minimize articular damage.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divine Ekwem ◽  
Thomas A. Morrison ◽  
Richard Reeve ◽  
Jessica Enright ◽  
Joram Buza ◽  
...  

AbstractIn Africa, livestock are important to local and national economies, but their productivity is constrained by infectious diseases. Comprehensive information on livestock movements and contacts is required to devise appropriate disease control strategies; yet, understanding contact risk in systems where herds mix extensively, and where different pathogens can be transmitted at different spatial and temporal scales, remains a major challenge. We deployed Global Positioning System collars on cattle in 52 herds in a traditional agropastoral system in western Serengeti, Tanzania, to understand fine-scale movements and between-herd contacts, and to identify locations of greatest interaction between herds. We examined contact across spatiotemporal scales relevant to different disease transmission scenarios. Daily cattle movements increased with herd size and rainfall. Generally, contact between herds was greatest away from households, during periods with low rainfall and in locations close to dipping points. We demonstrate how movements and contacts affect the risk of disease spread. For example, transmission risk is relatively sensitive to the survival time of different pathogens in the environment, and less sensitive to transmission distance, at least over the range of the spatiotemporal definitions of contacts that we explored. We identify times and locations of greatest disease transmission potential and that could be targeted through tailored control strategies.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S25-S26
Author(s):  
Angela L F Gibson ◽  
James H Holmes ◽  
Jeffrey W Shupp ◽  
David Smith ◽  
Victor Joe ◽  
...  

Abstract Introduction Autograft (AG) is the standard of care for treatment of severe burns. While AG provides effective wound closure (WC), the procedure creates a donor site wound prone to pain and scarring. In a phase 1b trial, no deep partial-thickness (DPT) wound treated with a bioengineered allogeneic cellularized construct (BACC) required AG by Day 28 and WC at the BACC site was achieved in 93% of patients by Month (M) 3. This phase 3 study (NCT03005106) evaluated the efficacy and safety of this BACC in patients with DPT burns. Methods Enrolled patients were aged ≥18 years with 3–49% TBSA thermal burns on the torso or extremities. In each patient, two DPT areas (≤2,000 cm2 total) deemed comparable following excision were randomized to treatment with either cryopreserved BACC or AG. Coprimary endpoints were 1) the difference in percent area of BACC treatment site and AG treatment site autografted at M3 and 2) the proportion of patients achieving durable WC of the BACC treatment site without AG at M3. Ranked secondary endpoints were: 1) the difference between BACC and AG donor sites in average donor site pain intensity through Day 14; 2) the difference between BACC and AG donor site cosmesis at M3; and 3) the difference between BACC and AG treatment site cosmesis at M12. Safety assessments were performed in all patients through M12. Results Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of BACC treatment sites that required AG, compared with AG treatment sites (4.3% vs 102.1%, respectively; P<.0001). BACC treatment resulted in durable WC at M3 without AG in 92% (95% CI: 85.6, 98.8; 59/64) of patients for whom data was available. By M3, mean donor site Patient and Observer Scar Assessment Scale (POSAS) observer total score (±SD) was significantly lower (more like normal skin) for BACC donor sites compared with AG donor sites (6.3 ± 1.71 vs 16.3 ± 7.71; P<.0001). At M12, mean POSAS observer total score (±SD) was 15.6 (± 8.34) for BACC treatment sites compared with 16.3 (± 9.41) for AG treatment sites (P=.4268). The most common BACC-related adverse event (AE) was pruritus, which occurred in 11 (15%) patients. All BACC-related AEs were mild or moderate in severity. Conclusions This phase 3 study achieved both coprimary endpoints, including significant autograft sparing and durable WC in DPT burns. Both donor site pain and donor site cosmesis were favorable outcomes of significantly reduced use of AG in BACC-treated patients. M12 POSAS for BACC did not differ significantly from AG. This BACC may offer a new treatment for severe burns to reduce or eliminate the need for AG. Applicability of Research to Practice This BACC has shown clinical benefit in patients with DPT thermal burns, potentially mitigating donor site morbidity. External Funding Stratatech, a Mallinckrodt Company; Funding and technical support for the Phase 3 clinical study were provided by the Biomedical Advanced Research and Development Authority (BARDA), under the Assistant Secretary for Preparedness and Response, within the U.S. Department of Health and Human Services, under Project BioShield Contract No. HHSO100201500027C.


Cartilage ◽  
2021 ◽  
pp. 194760352098877
Author(s):  
Roy D. Bloebaum ◽  
Andrew S. Wilson ◽  
William N. Martin

Objective There has been a debate as to the alignment of the collagen fibers. Using a hand lens, Sir William Hunter demonstrated that the collagen fibers ran perpendicular and later aspects were supported by Benninghoff. Despite these 2 historical studies, modern technology has conflicting data on the collagen alignment. Design Ten mature New Zealand rabbits were used to obtain 40 condyle specimens. The specimens were passed through ascending grades of alcohol, subjected to critical point drying (CPD), and viewed in the scanning electron microscope. Specimens revealed splits from the dehydration process. When observing the fibers exposed within the opening of the splits, parallel fibers were observed to run in a radial direction, normal to the surface of the articular cartilage, radiating from the deep zone and arcading as they approach the surface layer. After these observations, the same samples were mechanically fractured and damaged by scalpel. Results The splits in the articular surface created deep fissures, exposing parallel bundles of collagen fibers, radiating from the deep zone and arcading as they approach the surface layer. On higher magnification, individual fibers were observed to run parallel to one another, traversing radially toward the surface of the articular cartilage and arcading. Mechanical fracturing and scalpel damage induced on the same specimens with the splits showed randomly oriented fibers. Conclusion Collagen fiber orientation corroborates aspects of Hunter’s findings and compliments Benninghoff. Investigators must be aware of the limits of their processing and imaging techniques in order to interpret collagen fiber orientation in cartilage.


1977 ◽  
Vol 99 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Joseph M. Mansour ◽  
Van C. Mow

Fluid flow and mass transport mechanisms associated with articular cartilage function are important biomechanical processes of normal and pathological synovial joints. A three-layer permeable, two-phase medium of an incompressible fluid and a linear elastic solid are used to model the flow and deformational behavior of articular cartilage. The frictional resistance of the relative motion of the fluid phase with respect to the solid phase is given by a linear diffusive dissipation term. The subchondral bony substrate is represented by an elastic solid. The three-layer model of articular cartilage is chosen because of the known histological, ultrastructural, and biomechanical variations of the tissue properties. The calculated flow field shows that for material properties of normal healthy articular cartilage the tissue creates a naturally lubricated surface. The movement of the interstitial fluid at the surface is circulatory in manner, being exuded in front and near the leading half of the moving surface load and imbibed behind and near the trailing half of the moving load. The flow fields of healthy tissues are capable of sustaining a film of fluid at the articular surface whereas pathological tissues cannot.


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