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Acta Biomaterialia May 2024Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for...
Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. STATEMENT OF SIGNIFICANCE: Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.
Topics: Schwann Cells; Animals; Vascular Endothelial Growth Factor A; Nerve Regeneration; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Neovascularization, Physiologic; Rats; Transfection; Gelatin; Male; Tissue Scaffolds; Humans; Peripheral Nerve Injuries; Angiogenesis
PubMed: 38561075
DOI: 10.1016/j.actbio.2024.03.029 -
Acta Biomaterialia Apr 2024The reconstruction of posterior lamellar eyelid defects remains a significant challenge in clinical practice due to anatomical complexity, specialized function, and...
The reconstruction of posterior lamellar eyelid defects remains a significant challenge in clinical practice due to anatomical complexity, specialized function, and aesthetic concerns. The ideal substitute for the posterior lamellar should replicate the native tarsoconjunctival tissue, providing both mechanical support for the eyelids and a smooth surface for the globe after implantation. In this study, we present an innovative approach utilizing tissue-engineered cartilage (TEC) grafts generated from rabbit auricular chondrocytes and a commercialized type I collagen sponge to reconstruct critical-sized posterior lamellar defects in rabbits. The TEC grafts demonstrated remarkable mechanical strength and maintained a stable cartilaginous phenotype both in vitro and at 6 months post-implantation in immunodeficient mice. When employed as autografts to reconstruct tarsal plate defects in rabbits' upper eyelids, these TEC grafts successfully restored normal eyelid morphology, facilitated smooth eyelid movement, and preserved the histological structure of the conjunctival epithelium. When applied in bilayered tarsoconjunctival defect reconstruction, these TEC grafts not only maintained the normal contour of the upper eyelid but also supported conjunctival epithelial cell migration and growth from the defect margin towards the centre. These findings highlight that auricular chondrocyte-based TEC grafts hold great promise as potential candidates for clinical posterior lamellar reconstruction. STATEMENT OF SIGNIFICANCE: The complex structure and function of the posterior lamellar eyelid continue to be significant challenges for clinical reconstructive surgeries. In this study, we utilized autologous auricular chondrocyte-based TEC grafts for posterior lamellar eyelid reconstruction in a preclinical rabbit model. The TEC grafts exhibited native cartilaginous histomorphology and comparable mechanical strength to those of the native human tarsal plate. In rabbit models with either tarsal plate defects alone or bilayered tarsoconjunctival defects, TEC grafts successfully restored the normal eyelid contour and movement, as well as supported preservation and growth of conjunctival epithelium. This is the first study to demonstrate autologous TEC grafts can be employed for repairing tarsal plate defects, thereby offering an alternative therapeutic approach for treating posterior lamellar defects in clinic settings.
Topics: Animals; Rabbits; Eyelids; Plastic Surgery Procedures; Tissue Engineering; Cartilage; Transplantation, Autologous; Chondrocytes
PubMed: 38561072
DOI: 10.1016/j.actbio.2024.03.025 -
BioRxiv : the Preprint Server For... Mar 2024Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects...
Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and significantly increase surgical costs, adding to patients' already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 potentiated the effect of low dose BMP-2 to enhance osteogenic differentiation and mineralization of hMSCs . Standalone treatment with FK506 delivered on a collagen sponge, produced consistent bone bridging of a rat critically-sized femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging models, and indicate FK506 can be utilized either as a standalone treatment or in conjunction with rhBMP to treat a variety of spine disorders.
PubMed: 38559240
DOI: 10.1101/2024.03.08.584163 -
Scientific Reports Mar 2024Peripheral nerve injuries in the upper limb can lead to substantial disability and pain. We aimed to assess how socioeconomic factors affect outcomes after repaired or...
Peripheral nerve injuries in the upper limb can lead to substantial disability and pain. We aimed to assess how socioeconomic factors affect outcomes after repaired or reconstructed digital or major nerve trunk injuries in the upper limb. We identified 670 individuals, who underwent surgical nerve repair or reconstruction using sensory nerve autografts, in the Swedish National Quality Registry for Hand Surgery 2010-2018. Socioeconomic factors, including education, cohabitation, type of work, sick leave, immigrant status and income, were gathered from the Swedish statistical agency ( www.scb.se ) and National Diabetes Register (NDR). We calculated prevalence ratios (PR) to assess the relationship between socioeconomic factors and surgical outcomes for the nerve injuries. Individuals with a major nerve trunk injury had higher QuickDASH scores and lower income compared to those with digital nerve injury. Individuals with immigration background (adjusted PR = 2.0, 95% CI 1.2-3.2), history of > 4 weeks of sick leave the year before surgery (adjusted PR = 1.8, 95% CI 1.1-3.1), or education level below tertiary (adjusted PR = 2.8, 95% CI 1.7-4.7) had significantly higher QuickDASH scores. Recognizing impact of non-biological factors, including immigration, prior sick leave, and education level, on outcome after nerve surgery is crucial for improving prognosis in socioeconomically deprived individuals.
Topics: Humans; Peripheral Nerve Injuries; Upper Extremity; Plastic Surgery Procedures; Prognosis; Socioeconomic Factors
PubMed: 38538697
DOI: 10.1038/s41598-024-57757-w -
Annals of Joint 2023Anterior cruciate ligament (ACL) reconstruction has been widely used for ACL injury for a long time. However, residual rotational instability and osteoarthritic changes... (Review)
Review
Current development in surgical techniques, graft selection and additional procedures for anterior cruciate ligament injury: a path towards anatomic restoration and improved clinical outcomes-a narrative review.
BACKGROUND AND OBJECTIVE
Anterior cruciate ligament (ACL) reconstruction has been widely used for ACL injury for a long time. However, residual rotational instability and osteoarthritic changes after ACL reconstruction have been identified as problems. Thus, anatomic reconstruction techniques, various types of grafts and additional procedures have been desired to improve the clinical outcomes and knee instability. Although clinical outcomes and knee stability are better than in the past, ipsilateral graft failures still occur in 4-17% and osteoarthritic changes are seen in about 20% of patients after ACL reconstruction. To remedy these problems, it is necessary to improve the understanding of various surgical techniques and grafts and to pursue further improvement of surgical techniques. Therefore, the objective of this review is to summarize the advantages and disadvantages of various surgical techniques and graft selection, and additional procedures for ACL injury.
METHODS
A literature review was conducted on the surgical procedures for ACL injury. Recent trends in surgical techniques, graft selection, and additional procedures for ACL injury were described. We performed a literature search in PubMed for studies published from origin to May 8, 2023. Studies were required to be English-language articles.
KEY CONTENT AND FINDINGS
Although many reports indicate that double-bundle ACL reconstruction is comparable to anatomic single-bundle (SB) reconstruction, intraoperative complications such as tunnel coalition exist in double-bundle reconstruction, and the technique needs to be improved. ACL repair has shown good short-term results, but long-term results need to be examined in the future. Quadriceps tendon autograft is being used more frequently, but hamstrings tendon autograft and bone-patellar tendon-bone autograft also have good results. In addition, in higher-risk cases, lateral extra-articular tenodesis (LET) and anterolateral ligament (ALL) reconstruction can be performed with good results.
CONCLUSIONS
To further improve clinical outcomes, more anatomical reconstructions should be pursued. Autografts are better than allografts and synthetic grafts, but further study is needed to determine which graft is better. Additional procedures should be performed in highly unstable cases and in revision cases.
PubMed: 38529242
DOI: 10.21037/aoj-23-39 -
Annals of Joint 2023Injury to the anterior cruciate ligament (ACL) of the knee is common and often requires surgical reconstruction. There are numerous graft options available to the... (Review)
Review
Injury to the anterior cruciate ligament (ACL) of the knee is common and often requires surgical reconstruction. There are numerous graft options available to the operating surgeon, to each of which a growing body of dedicated literature exists. Each of these potential choices of ACL graft specimen has a distinctive set of biomechanical properties, clinical outcome profiles, and other special considerations (e.g., autograft versus allograft, harvest site factors, and operating time). The purpose of this review is to discuss the biomechanical characteristics of the native ACL alongside those of several of the most commonly used ACL graft specimens based on a current review of the biomechanical literature. In doing so, this review will also briefly discuss the biomechanical implications for allograft versus autograft usage and single-bundle versus double-bundle repair techniques. This review lists and discusses the stress, strain, stiffness, Young's modulus, and ultimate load to failure of the native ACL, several common autografts [patellar bone-tendon-bone (BTB), hamstring tendon (HT), and quadriceps tendon (QT)], and several common allografts. Given the important biomechanical role of the ACL in stabilizing the knee to translational and rotational forces, it is crucial that the operating surgeon make a decision on graft choice that is informed in the biomechanical implications of ACL graft selection.
PubMed: 38529237
DOI: 10.21037/aoj-22-50 -
Annals of Joint 2023Graft selection for anterior cruciate ligament reconstruction (ACLR) affects rehabilitation throughout the course of postoperative care. (Review)
Review
BACKGROUND AND OBJECTIVE
Graft selection for anterior cruciate ligament reconstruction (ACLR) affects rehabilitation throughout the course of postoperative care.
METHODS
A search of PubMed and EBSCO was performed and abstracts independently reviewed by two authors. This search was also supplemented with additional evidence relevant to each phase of ACLR rehabilitation.
KEY CONTENT AND FINDINGS
Direct implications of graft type on clinical decisions vary throughout treatment phases, transitioning from potential differences in acute postoperative pain management immediately after surgery to facilitating sufficient and appropriate lower extremity loading in subsequent weeks. Regardless of graft type, surgical limb weakness persists throughout the course of rehabilitation; however, harvest site selection for autografts contributes to disproportionate weakness of the harvested muscle group and the potential for surgical-induced tendinopathy. In later phases of rehabilitation, as athletes are transitioning into return to sport (RTS), treatment decisions and protocols are less affected by graft type but expectations for meeting clinical milestones and the time required to do so does differ between graft types.
CONCLUSIONS
Targeted strengthening interventions to address muscle weakness following graft harvest in autografts should be continued throughout the rehabilitation process. Lingering deficits in quadriceps strength symmetry may also influence time to meet progression and RTS criteria following graft harvest from the extensor mechanism.
PubMed: 38529227
DOI: 10.21037/aoj-22-51 -
Arthroscopy, Sports Medicine, and... Apr 2024To compare postoperative knee stability, functional outcomes, and complications after anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone... (Review)
Review
Both Quadriceps and Bone-Patellar Tendon-Bone Autografts Improve Postoperative Stability and Functional Outcomes After Anterior Cruciate Ligament Reconstruction: A Systematic Review.
PURPOSE
To compare postoperative knee stability, functional outcomes, and complications after anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BPTB) versus quadriceps tendon autograft.
METHODS
In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, the PubMed, Embase, and Cochrane Library databases were searched for studies published in 2002 or later. Studies were included if they met the following criteria: randomized controlled trials that included patients who underwent ACL reconstruction with BPTB or quadriceps tendon autograft including all soft tissue and bone-quadriceps tendon and in which measures of postoperative stability and functional outcomes were reported. Studies that were not written in English and those that analyzed animals or cadavers, were not randomized controlled trials, or used other grafts (e.g., hamstring) were excluded.
RESULTS
The initial search identified 348 studies, 6 of which were included in this systematic review. Two of the six studies found no significant difference in performance outcomes or complications between quadriceps and BPTB autografts. One study found that patients receiving quadriceps autograft self-reported improved knee functional status compared with those receiving BPTB autograft. Another study found that quadriceps autograft resulted in a significantly reduced Quadriceps Index postoperatively compared with BPTB autograft (69.5 vs 82.8, = .01) but found no difference in postoperative quadriceps strength. An additional study found that the outcomes of quadriceps tendon and BPTB autografts were equivalent per the International Knee Documentation Committee scale, but anterior knee pain was less severe in patients with quadriceps tendon autograft. Furthermore, one study revealed the overall International Knee Documentation Committee score was reported as normal significantly more often in patients who underwent ACL reconstruction with BPTB autograft (85% vs 50%, < .001) and that donor-site morbidity was greater in patients with quadriceps autograft. No significant difference was found in complications requiring reoperation across studies.
CONCLUSIONS
Patients undergoing ACL reconstruction with either BPTB or quadriceps tendon autograft reported improved postoperative knee stability and functional outcomes. There is no significant difference in complications between quadriceps autograft use and BPTB autograft use.
LEVEL OF EVIDENCE
Level III, systematic review of Level III retrospective studies.
PubMed: 38525287
DOI: 10.1016/j.asmr.2024.100919 -
Orthopaedic Journal of Sports Medicine Mar 2024Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include...
BACKGROUND
Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include the palmaris longus (PL) and hamstring tendons. Allograft use may reduce donor site morbidity and decrease function related to PL autografts.
PURPOSE
To compare varus stability and load to failure between a novel allograft for UCLR-knee medial collateral ligament (kMCL)-and a PL autograft in human donor elbow specimens.
STUDY DESIGN
Controlled laboratory study.
METHODS
A total of 24 fresh-frozen human elbows were dissected to expose the mUCL. Medial elbow stability was tested with the mUCL intact (native), deficient, and reconstructed utilizing the humeral single-docking technique with either a (1) kMCL allograft (n = 12) or (2) a PL autograft (n = 12). A 3-N·m valgus torque was applied to the elbow, and valgus rotation of the ulna was recorded via motion tracking cameras. The elbow was cycled through a full range of motion 5 times. After kinematic testing, specimens were loaded to failure at 70° of elbow flexion, and failure modes were recorded.
RESULTS
The mUCL-deficient elbows demonstrated significantly greater valgus rotation compared with the intact and reconstructed elbows at every flexion angle tested (10°-120°) ( <.001). Both kMCL- and PL-reconstructed elbows exhibited significantly higher mean valgus rotation compared with the intact state between 10° and 40° of flexion ( < .01). There were no significant differences in valgus rotation at any flexion angle between the kMCL and PL graft groups. When loaded to failure, elbows reconstructed with both kMCL and PL grafts failed at similar torque values (18.6 ± 4 and 18.1 ± 3.4 N·m, respectively; = .765).
CONCLUSION
Fresh-frozen and aseptically processed kMCL allografts demonstrated similar kinematic and failure properties to PL tendon autografts in UCL-reconstructed elbows, although neither graft fully restored kinematics between 10° and 40°.
CLINICAL RELEVANCE
Prepared kMCL ligament allografts may provide a viable graft material when reconstructing elbow ligaments while avoiding the potential complications related to PL autografts- including donor site morbidity.
PubMed: 38524888
DOI: 10.1177/23259671241234685