Tendon-bone interface healing using an injectable rhBMP-2-containing collagen gel in a rabbit extra-articular bone tunnel model

2015 ◽  
Vol 11 (5) ◽  
pp. 1435-1441 ◽  
Author(s):  
Kwang Won Lee ◽  
Jung Soo Lee ◽  
Ju Woong Jang ◽  
Young Bock Shim ◽  
Kwang-Il Lee
Keyword(s):  
Collagen Gel ◽  
Bone Tunnel ◽  
Bone Interface ◽  
Tunnel Model

scholarly journals Fibrin Glue-Kartogenin Complex Promotes the Regeneration of the Tendon-Bone Interface in Rotator Cuff Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jun Zhu ◽  
Jiahua Shao ◽  
Yi Chen ◽  
Guangyi Zhao ◽  
Lexiang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Fibrin Glue ◽  
Tendon Graft ◽  
Bone Tunnel ◽  
Rotator Cuff Tendon ◽  
Bone Interface ◽  
Tunnel Model ◽  
Rotator Cuff Injury

Objective. Rotator cuff injury healing is problematic because the tendon-bone junction often forms cicatricial tissues, rather than fibrocartilage, which leads to mechanical impairment and is prone to redamage. Kartogenin (KGN) is a newly discovered small molecule compound which can induce cartilage formation through chondrogenesis of endogenous mesenchymal stem cells. Methods. In this study, we used KGN with fibrin glue (FG) to repair the rotator cuff injury by promoting the formation of fibrocartilage at the tendon to bone interface. Firstly, we assessed the release rate of KGN from the FG-KGN complex and then created a rabbit rotator cuff tendon graft-bone tunnel model. The rabbits received saline, FG-KGN, or FG injections onto the tendon to bone interface after injury. Shoulder tissues were harvested at 6 and 12 weeks, and the sections were stained with HE and Safranin O/Fast green. The samples were assessed by histologic evaluation and biomechanical testing. Synovial mesenchymal stem cells derived from the synovial tissue around the rotator cuff were harvested for western blotting and qRT-PCR analysis. Results. KGN was released rapidly from the FG-KGN complex during first 4 hrs and followed by a slow release until 7 days. The tendon graft-bone interface in the control (saline) group and the FG group was filled with scar tissue, rather than cartilage-like tissue, and only a small number of chondrocytes were found at the adjacent bone surface. In the FG-KGN group, the tendon to bone interface was fully integrated and populated by chondrocytes with proteoglycan deposition, indicating the formation of fibrocartilage-like tissues. At 12 weeks, the maximum tensile strength of the FG-KGN group was significantly higher than that of the FG and control groups ( P < 0.01 ). The RNA expression levels of tendinous genes such as Tenascin C and the chondrogenic gene Sox-9 were substantially elevated in SMSCs treated with the FG-KGN complex compared to the other two groups. Conclusion. These results indicated that fibrin glue is an effective carrier for KGN, allowing for the sustained release of KGN. The FG-KGN complex could effectively promote the regeneration and formation of fibrocartilage tissue of the tendon-bone interface in the rabbit rotator cuff tendon graft-bone tunnel model.

Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells

2019 ◽  
Vol 47 (11) ◽  
pp. 2729-2736
Author(s):  
Jun Lu ◽  
Connie S. Chamberlain ◽  
Ming-liang Ji ◽  
Erin E. Saether ◽  
Ellen M. Leiferman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Healing ◽  
Macrophage Polarization ◽  
Group Versus ◽  
Autologous Bone Marrow ◽  
Bone Tunnel ◽  
Control Group ◽  
M2 Macrophage ◽  
Bone Interface ◽  
Autologous Bone

Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM. Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model. Study Design: Controlled laboratory study. Methods: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery. Results: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks ( P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group ( P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery ( P < .05). Load to failure showed similar trends to stiffness. Conclusion: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization. Clinical Relevance: Fresh autologous BM could be a treatment option for this disorder.

Augmentation of Tendon Graft–Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds

2020 ◽  
Vol 48 (6) ◽  
pp. 1379-1388
Author(s):  
Chin-Chean Wong ◽  
Yi-Yen Yeh ◽  
Tsung-Lin Yang ◽  
Yang-Hwei Tsuang ◽  
Chih-Hwa Chen
Keyword(s):  
Bone Healing ◽  
Type I Collagen ◽  
Tendon Graft ◽  
Bone Tunnel ◽  
Activity Level ◽  
Type I ◽  
Micro Ct ◽  
Gene Expressions ◽  
Platelet Rich Fibrin ◽  
Bone Interface

Background: Platelet-rich fibrin (PRF) is a bioactive biomaterial wherein cytokines are enmeshed within the interconnecting fibrin network. PRF can be fabricated into a patch to augment healing of the interface between a tendon graft and bone tunnel. Hypothesis: The bioactivity of a PRF scaffold is preserved after PRF is mechanically compressed into a patch. A bioactive PRF patch could promote the incorporation of a tendon graft within the bone tunnel through the formation of a tendon-bone healing zone composed of both fibrocartilaginous tissue and new bone. Study Design: Controlled laboratory study. Methods: Bioactivity of PRF was evaluated through treatment of rabbit tenocytes with PRF-conditioned medium and cultivation of cells on a PRF patch. Cellular morphologic features, viability, and differentiation were analyzed accordingly. In an animal study, a rabbit tendon-bone healing model was established through use of New Zealand White rabbits. The implanted tendon graft was enveloped circumferentially with a bioactive PRF patch before being pulled through a bone tunnel in the proximal tibia. Micro–computed tomography (micro-CT) imaging and histological and biomechanical analyses of the tendon-bone interface were performed at 12 weeks postoperatively. Results: PRF improved the viability of the cultured tenocytes. The effects of PRF on in vitro mineralization of tenocytes were comparable with the effects of standard culture medium. The gene expressions of type I collagen and osteopontin were upregulated upon PRF treatment. For the in vivo study, micro-CT images revealed significant new bone synthesis at the tendon-bone interface in the PRF-enveloped group. The tendon-bone healing zone was characterized by abundant fibrocartilage tissue and new bone formation as demonstrated by histological analysis. Biomechanical testing showed significantly higher ultimate loads in the PRF-enveloped group. Conclusion: Bioactive PRF could effectively augment healing of tendon graft to bone by inducing the formation of a transitional tendon-bone healing zone composed of fibrocartilage and bone. Clinical Relevance: Complete healing of the tendon graft in the bone tunnel is a prerequisite for successful ligament reconstruction, which would allow early and aggressive rehabilitation and rapid return to preinjury activity level. From a translational standpoint, the PRF-augmented healing in this rabbit animal model showed a promising biological approach to enhance tendon graft to bone healing via promotion of the functional anchorage between the 2 different materials.

ENCAPSULATION OF PERIOSTEAL STEM CELLS IN INJECTABLE PHOTOPOLYMERIZED HYDROGEL ENHANCES TENDON GRAFT OSTEOINTEGRATION

2006 ◽  
Vol 10 (03) ◽  
pp. 109-120
Author(s):  
Hsia-Wei Liu ◽  
Chih-Hwa Chen ◽  
Ching-Lin Tsai ◽  
Chung-Ming Yu ◽  
I-Hsuan Lin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bone Healing ◽  
Proximal Tibia ◽  
Biomechanical Testing ◽  
Tendon Graft ◽  
Bone Tunnel ◽  
Matrix Composition ◽  
Primary Concern ◽  
Bone Interface ◽  
Pull Out

Photopolymerized hydrogel based on poly(ethylene glycol) diacrylate (PEGDA) was applied to periosteum-derived periosteal stem cell (PSC) encapsulation and orthopedic tissue engineering. To provide support for cell adhesion, hyaluronic acid (HA) was incorporated into the PEGDA solution prior to photopolymerization. HA can be utilized to mimic the extracellular matrix composition as well as control cell growth and differentiation. In vitro studies have demonstrated its ability to encapsulate PSCs to form bone-like tissue in a photopolymerized hydrogel. Osteointegration of a tendon graft within the bone tunnel is a primary concern when employing tendon grafts for ligament reconstruction. This study presents a novel technique for fabricating injectable hydrogel–photoencapsulated PSCs in a bone tunnel to enhance tendon–bone healing. A total of 21 adult New Zealand white rabbits were used. The long extensor digitorum tendon was transplanted into a bone tunnel of the proximal tibia. The tendon was pulled through a drill hole in the proximal tibia and attached to the medial aspect of the tibia. Hydrogel suspension containing PSCs at a concentration of 20 million/mL was injected into the bone tunnel. Histological examination of the tendon–bone interface and biomechanical testing for maximal pull-out load were evaluated at postoperative weeks 3 and 6. Histological analysis of the tendon–bone interface showed an interface fibrous layer formed by the photoencapsulation of PSCs between the tendon and the bone. This layer became progressive integrated with the tendon–bone surface during the healing process. Biomechanical testing revealed higher maximal pull-out strength in experimental groups with a statistically significant difference at 3 and 6 weeks. These results suggest that photopolymerizable PEGDA and HA hydrogels are promising for tissue-engineered stem cell therapy to enhance tendon–bone healing.

scholarly journals Tendon Healing in Bone Tunnel after Human Anterior Cruciate Ligament Reconstruction: A Systematic Review of Histological Results

2018 ◽  
Vol 32 (05) ◽  
pp. 454-462 ◽  
Author(s):  
Hongbin Lu ◽  
Can Chen ◽  
Shanshan Xie ◽  
Yifu Tang ◽  
Jin Qu
Keyword(s):  
Systematic Review ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Healing Process ◽  
Tendon Healing ◽  
Tendon Graft ◽  
Bone Tunnel ◽  
Bone Interface ◽  
Graft Healing ◽  
Anterior Cruciate

AbstractMost studies concerning to tendon healing and incorporation into bone are mainly based on animal studies due to the invasive nature of the biopsy procedure. The evidence considering tendon graft healing to bone in humans is limited in several case series or case reports, and therefore, it is difficult to understand the healing process. A computerized search using relevant search terms was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies that investigated tendon graft healing to bone by histologic examination after anterior cruciate ligament (ACL) reconstruction with hamstring. Ten studies were determined to be eligible for this systematic review. Thirty-seven cases were extracted from the included studies. Most studies showed that a fibrovascular interface would form at the tendon–bone interface at the early stage and a fibrous indirect interface with Sharpey-like fibers would be expected at the later stage. Cartilage-like tissue at tendon graft–bone interface was reported in three studies. Tendon graft failed to integrate with the surrounding bone in 10 of the 37 cases. Unexpectedly, suspensory type of fixation was used for the above failure cases. An indirect type of insertion with Sharpey-like fibers at tendon–bone interface could be expected after ACL reconstruction with hamstring. Regional cartilage-like tissue may form at tendon–bone interface occasionally. The underlying tendon-to-bone healing process is far from understood in the human hamstring ACL reconstruction. Further human studies are highly needed to understand tendon graft healing in bone tunnel after hamstring ACL reconstruction.

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

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