Correlation between articular cartilage status on outcomes and survivorship following meniscal allograft transplantation: A systematic review.

PURPOSE: To conduct a systematic review evaluating potential correlations between preoperative articular cartilage integrity on outcomes and survivorship in patients undergoing meniscal allograft transplantation (MAT). METHODS: A literature search was performed by querying SCOPUS, PubMed, Medline, and the Cochrane Central Register for Controlled Trials from database inception through May 2023 according to the 2020 PRISMA statement. Inclusion criteria were limited to studies reporting on outcomes and survivorship following MAT based on preoperative cartilage status. RESULTS: Sixteen studies, consisting of 1723 patients (n = 1758 total menisci), were identified in six level III and 10 level IV evidence studies. There was high heterogeneity in cartilage grading scales, reporting of concomitant cartilage procedures, and indications for MAT based on osteoarthritis. Patients with lower limb malalignment were either excluded or corrected with an osteotomy. MAT failure rate was reported in nine studies, with four studies reporting a greater rate of failure in knees with higher degrees of cartilage damage. Eight studies reported on clinical outcomes based on cartilage grade, with two studies reporting significant differences in clinical outcomes based on cartilage grade. Of the five studies reporting management of full-thickness chondral defects with cartilage surgery, three studies reported no significant difference in survivorship based on preoperative cartilage grade, while one study reported lower survivorship and one study reported unclear results. No studies found significant differences in survivorship and outcomes between medial and lateral MAT. CONCLUSIONS: Conflicting results and high variability in reporting of concomitant cartilage repair and indications for MAT exist in studies evaluating the efficacy of MAT based on articular cartilage status. The degree of preoperative chondral damage did not have a strong relationship with clinical outcomes following MAT. Higher degrees of cartilage damage were associated with higher MAT failure rates, with possible improvement in survivorship when treated with an appropriate cartilage procedure. LEVEL OF EVIDENCE: Level IV.

Survivorship of 157 Arthroscopic Meniscal Allograft Transplants Using Bone Fixation at a Mean of 7 Years and Prognostic Factors Analysis.

BACKGROUND: Meniscal allograft transplantation (MAT) is an accepted and effective treatment option in the context of unsalvageable menisci, particularly in young and active patients. It has been shown to reduce pain and improve knee function in previously symptomatic patients. However, there is still limited knowledge about the long-term survival rates of allografts, the durability of clinical results, and the influence of patient-specific parameters, such as leg alignment, tibial slope, and preoperative International Cartilage Regeneration & Joint Preservation Society (ICRS) grade. PURPOSE: To determine (1) the long-term clinical success rate after MAT with bony fixation in a large, single-center cohort of consecutive patients, and (2) if patient-specific and procedural variables influence the clinical, anatomic, and subjective outcomes and risk of failure. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data on 185 consecutive knees undergoing MAT in a single institution were prospectively collected and screened for inclusion in this study. The minimum follow-up time was 2 years. Radiographic variables (ICRS grade and Kellgren-Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (PROMs) (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale [VAS] score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery due to graft failure or conversion to total knee arthroplasty. Anatomic failure was considered a tear covering >20% of the allograft, any peripheral tear, and unstable peripheral fixation leading to dislocation of the graft. Subjective failure was defined as Lysholm score ≤65. Preoperative tibial slope and leg alignment were assessed. Survival analyses were performed using the Kaplan-Meier estimate. Univariate and multivariate analyses were performed to determine risk factors for clinical and anatomic failure. RESULTS: A total of 157 knees met inclusion criteria. After a mean follow-up time of 7 ± 3.5 years, 127 (80.9%) knees were free of clinical, anatomic, and subjective failure. Fourteen (8.9%) knees experienced clinical failure, 26 (16.6%) knees were identified as having experienced anatomic failure, and 13 (8.3%) patients experienced subjective failure with a reported Lysholm score of ≤65 at a mean follow-up of 7 years. Concurrent osteochondral allograft transplantation was identified as a predictor of both clinical (hazard ratio [HR], 4.55; 95% CI, 1.46-14.17; P = .009) and anatomic (HR, 3.05; 95% CI, 1.34-6.92; P = .008) failure. Cartilage damage of ICRS grade 3 or 4 of the index compartment conveyed an increased risk for clinical (HR, 3.41; 95% CI, 1.05-11.01; P = .04) and anatomic (HR, 3.04; 95% CI, 1.31-7.11; P = .01) failure. High-grade cartilage damage preoperatively (HR, 10.67; 95% CI, 1.037-109.768; P = .046), patient age >25 years (HR, 5.44; 95% CI, 0.120-246.070; P = .384), and a body mass index >30 (HR, 2.24; 95% CI, 0.748-6.705; P = .149) were associated with subjective failure. PROMs including KOOS and IKDC were significantly improved at final follow-up compared with preoperative scores across all measurements (P < .005). CONCLUSION: MAT showed good to excellent clinical results at a mean follow-up of 7 years. Low ICRS lesion grade was associated with a higher clinical and anatomic survival rate. Patients with concurrent OCA transplantation are at a higher risk of clinical and anatomic failure, but still report significantly improved PROMs. These results suggest that MAT has a lasting beneficial effect both in isolation and in complex cases with ≥1 concurrent procedures.

The effectiveness of acellular nerve allografts compared to autografts in animal models: A systematic review and meta-analysis.

BACKGROUND: Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft. OBJECTIVE: To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications. MATERIAL AND METHODS: PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species. RESULTS: Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design. CONCLUSION: Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, > 1-2cm) nerve gaps is preferred over an allograft in long (> 2cm) nerve gaps.

Dehydrated human amnion/chorion membrane allograft with spongy layer to significantly improve the outcome of chronic non-healing wounds.

We investigated the healing effect of a new dehydrated amnion/chorion membrane with a spongy layer over a 30-month period in 32 patients with 53 chronic non-healing wounds of different aetiologies. Wounds with <40% surface reduction after 4 weeks of best wound treatment underwent weekly allograft application by a certified wound specialist based on national guidelines and a standardised protocol until complete healing or definite treatment interruption. The main outcome measure was the percentage of wound surface reduction from baseline calculated using digital planimetry follow-up photographs. Overall, 38 (71.7%) wounds presented a favourable outcome (70%-100% area reduction), with 35 (66%) completely healing over a median time of 77 days (range 29-350 days). Favourable outcomes were observed in 75% of traumatic wounds, surgical wounds, venous leg ulcers and pressure injuries, as well as in 50% of ischaemic wounds. Wounds being present <12 months were significantly more likely to have a favourable outcome than more long-standing wounds (χ2 = 7.799; p = 0.005; OR = 3.378; 95% CI, 1.410-8.092). Thus, treatment with dehydrated amnion/chorion membrane with a spongy layer improves the outcome of non-healing wounds of different aetiologies and, therefore, has to be considered early in the management of refractory wounds.

Unique Usages of Dehydrated Human Amnion Chorion Membrane Allografts in Dermatology.

Dehydrated human amnion chorion membrane (dHACM) allografts are synthetic skin substitutes derived from placental tissue. dHACM allografts are used for replacing lost or damaged dermal tissue, as they contain many of the components found within the extracellular matrix that are beneficial in wound healing. Common uses of dHACM allografts include the healing of diabetic and non-diabetic foot and leg ulcers, decubitus ulcers, and wounds following debridement. While these grafts have been proven to be beneficial in other disciplines of medicine, their potential for use in the field of dermatology is emerging. Current clinical cases and research have shown dHACM allografts to be beneficial in repairing damaged tissue due to dermatologic conditions. They could play a role in the treatment of conditions causing chronic wounds, including dermal scarring or loss, and the repair of fragile skin. Examples of dHACM allograft use in dermatology include cases of pyoderma gangrenosum, Netherton syndrome, and wound healing with Mohs micrographic surgery. This literature review explores the efficacy of using dHACM allografts for the treatment of healing wounds within the field of dermatology. J Drugs Dermatol. 2023;22(12):1228-1231. doi:10.36849/JDD.7115.

Survival rate of implants following maxillary sinus floor augmentation using freeze-dried allografts vs bovine derived xenografts: A retrospective multicenter study.

INTRODUCTION: This study aims to compare the surgical and clinical complications, and the dental implant survival rate after maxillary sinus floor augmentation using demineralized freeze-dried bone allografts (DFDBA) versus bovine derived xenografts. MATERIAL AND METHODS: A retrospective study enrolled 107 patients (52 males and 55 females, mean age group 1: 54,4 years; group 2: 56,4 years) requiring maxillary bone reconstruction prior to implantation. A total of 141 sinuses were grafted and 191 implants were placed. Data on various variables, including patient characteristics, implant placement details, and outcomes, were collected through medical records and patient questionnaires. RESULTS: The study found no significant differences in implant survival rates between the two groups (94,0% versus 94,4%; p = 0,919). Overall complications were observed in 19.6% of patients, with a higher incidence in the allograft group (23,6% versus 15,4%; p = 0,283). Multiple logistic regression analysis identified a two-stage surgical protocol (OR= 2,8; p = 0,045), and a preoperative alveolar ridge height of less than 4 mm (OR= 5,3; p = 0,004) as significant predictors of complications. The risk of implant failure was raised by a preoperative alveolar ridge height of less than 4 mm (OR= 6,1; p = 0,038) and smoking (OR= 5,8; p = 0,012). DISCUSSION: DFDBA is a reliable treatment option for extensive rehabilitation of atrophic maxilla, with a success rate comparable to xenografts used in sinus augmentation. Implant failure was significantly correlated with smoking and a residual ridge height of less than 4 mm.

Application of platelet-rich fibrin and freeze-dried bone allograft following apicoectomy: A comparative assessment of radiographic healing.

Background: Apicoectomy conceptualizes surgically maintaining a tooth with an endodontic lesion that cannot be resolved by conventional endodontic (re-) treatment. To achieve this, continuous improvement in surgical techniques, materials and instruments is being done to enhance the outcome of periapical endodontic surgeries. The purpose of this study was to compare, radiographically, the healing kinetics of platelet-rich fibrin (PRF) and mineralized freeze-dried bone allograft (FDBA) in patients undergoing apicoectomy. Materials and Methods: Nineteen patients (aged 18-40 years) were included in the study and randomly assigned to groups A or B, where they received PRF or FDBA, respectively. Following apicoectomy, PRF gel and FDBA graft were prepared and placed in the osseous defect followed by placement of PRF membrane for graft stabilization and flap closure. Radiographic follow-up was done at the 1st, 3rd, 6th and 12th months for evaluation of healing using Molven's criteria. Statistical analysis was done with Pearson's and McNemar's Chi-square tests. Results: A highly significant difference (P = 0.002) in radiographic healing was observed at 6 months. Complete healing was observed in 50% of cases in Group A whereas in Group B, none of the cases presented with complete radiographic healing. However, at the end of 12 months, complete radiographic healing was observed in both groups. Conclusion: Our data suggest that PRF accelerates bone healing as compared to FDBA and is both time and cost-efficient.

Survivorship After Lateral Meniscal Allograft Transplantation Plus Concurrent Cartilage Procedure in Patients With Poor Cartilage Status: A Comparative Study.

BACKGROUND: The effect of a concurrent cartilage procedure in lateral meniscal allograft transplantation (MAT) in patients with bipolar cartilage lesions (high-grade lesions on both the femoral and the tibial side) is not well studied. An objective evaluation of graft status after MAT and a concurrent cartilage procedure has not been reported. PURPOSE: To investigate the effect of concurrent cartilage procedures and lateral MAT on objective and clinical outcomes, including survival, in patients with bipolar cartilage lesions. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 149 patients with high-grade (International Cartilage Regeneration & Joint Preservation Society grade 3 or 4) cartilage lesions were enrolled and assigned to 1 of 3 groups based on the cartilage procedure and cartilage status at the time of MAT. Femoral cartilage procedures (microfracture, n = 18; osteochondral autograft transfer, n = 13) and lateral MAT were performed in 31 patients with bipolar cartilage lesions (cartilage procedure group). Another 70 patients with bipolar lesions underwent only lateral MAT without cartilage procedure (bipolar lesion group). The remaining 48 patients, who had high-grade lesions only on the tibial side and underwent lateral MAT without a cartilage procedure, were selected as a control group (unipolar lesion group). Anatomic survival was objectively assessed by follow-up magnetic resonance imaging and second-look arthroscopy. Clinical survivorship was determined with a Lysholm score <65 or need for additional surgery, such as revision MAT. RESULTS: The mean Lysholm score improved from 67.2 ± 15.9 preoperatively to 86.7 ± 11.1 with a mean follow-up of 78.0 ± 51.2 months (P < .001). The postoperative scores were not significantly different between the 3 groups. The estimated 5-year anatomic survival rate in the cartilage procedure group (86.7%) was higher than that in the bipolar lesion group (65.0%; P = .043) but comparable with that in the unipolar lesion group (90.2%; P = .572). The estimated 5-year clinical survival rates were not significantly different between the groups (P = .187). CONCLUSION: A concurrent femoral cartilage procedure improved the anatomic survival rate in patients with bipolar chondral lesions who underwent lateral MAT. This finding suggests that the cartilage procedure is an effective treatment choice and may improve the status of an allograft after lateral MAT for patients with bipolar cartilage lesions.

Alveolar Ridge Preservation Procedures Performed with a Freeze-Dried Bone Allograft: Histologic Outcomes in a Cohort Study.

The primary aim of this study was to assess the histomorphometric outcomes of extraction sockets grafted with freeze-dried bone allograft (FDBA) and sealed with a collagen membrane after 3 months of healing in specific region of interest (ROI) areas. The secondary aims were to analyze the biomaterial resorption rate, the bone-to-biomaterial contact (BBC), and the area and perimeter of grafted particles compared with commercially available FDBA particles. Fifteen patients underwent tooth extractions and ridge preservation procedures performed with FDBA and a collagen membrane. Bone biopsy samples were harvested after 3 months at the time of implant placement for histologic and histomorphometric analysis. Two areas of concern (ROI1 and ROI2) with different histologic features were identified within the biopsy samples; ROI1, ROI2, and commercially available particles were analyzed and compared. The following parameters were analyzed: newly formed bone, marrow space, residual graft particles, perimeter and area of FDBA particles, and BBC. The histomorphometric analysis showed 35.22% ± 10.79% newly formed bone, 52.55% ± 16.06% marrow spaces, and 12.41% ± 7.87% residual graft particles. Moreover, the histologic data from ROI1 and ROI2 showed that (1) the mean percentage of BBC was 64.61% ± 27.14%; (2) the newly formed bone was significantly higher in ROI1 than in ROI2; (3) the marrow space was significantly lower in ROI1 than in ROI2; and (4) the FDBA particles in ROI1 sites showed significantly lower area and perimeter when compared to commercially available FDBA particles. This latter data led to the hypothesis that FDBA particles embedded in newly formed bone undergo a resorption/remodeling process.

Enhancing Functional Recovery after Segmental Nerve Defect Using Nerve Allograft Treated with Plasma-Derived Exosome.

BACKGROUND: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. METHODS: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. RESULTS: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. CONCLUSIONS: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair. CLINICAL RELEVANCE STATEMENT: Off-the-shelf exosomes may improve recovery in nerve allografts.

Injectable platelet-rich fibrin with demineralized freeze-dried bone allograft compared to demineralized freeze-dried bone allograft in intrabony defects of patients with stage-III periodontitis: a randomized controlled clinical trial.

AIM: The current randomized controlled clinical trial assessed the effect of injectable platelet-rich fibrin (I-PRF) combined with demineralized freeze-dried bone allograft (DFDBA) compared to DFDBA alone in the management of intrabony defects of stage-III periodontitis patients. METHODOLOGY: Following sample size calculation, twenty stage-III periodontitis patients with ≥ 5 mm clinical attachment level (CAL)-loss and ≥ 3 mm intrabony defects were randomized into test (I-PRF + DFDBA; n = 10) and control (DFDBA; n = 10) groups. CAL (primary outcome), periodontal probing depth (PPD), gingival recession depth (GRD), full-mouth plaque scores (FMPS), full-mouth bleeding scores (FMBS), radiographic linear defect depth (RLDD), and bone fill (secondary outcomes) were examined at baseline, 3, 6, and 9 months post-surgically. RESULTS: I-PRF + DFDBA and DFDBA independently demonstrated significant intragroup CAL-gain, PPD-, and RLDD-reduction at 3, 6, and 9 months (p < 0.05), with no significant intergroup differences observed (p > 0.05). CAL-gain (mean ± SD) of 2.40 ± 0.70 mm and 2.50 ± 0.85 mm and PPD-reduction of 3.50 ± 1.18 mm and 2.80 ± 0.42 mm were demonstrated for I-PRF + DFDBA and DFDBA at 9 months respectively. Both groups showed significant intragroup RLDD improvement, with a RLDD of 3.58 ± 0.66 mm and 3.89 ± 1.57 mm for I-PRF + DFDBA and DFDBA at 9 months respectively. Stepwise linear regression analysis revealed that baseline RLDD and bone fill at 9 months were significant predictors of CAL (p < 0.05). CONCLUSION: Within the present study's limitations, DFDBA with or without I-PRF resulted in significant improvement in clinical and radiographic periodontal parameters in the surgical treatment of periodontal intrabony defects of stage-III periodontitis patients. Addition of I-PRF to DFDBA does not appear to significantly enhance the DFDBA's reparative/regenerative outcomes. CLINICAL RELEVANCE: Within the current study's limitations, routinely adding I-PRF to DFDBA cannot be recommended to significantly improve DFDBA's treatment outcomes in intrabony defects.

A Systematic Review and Meta-Analysis of Nerve Gap Repair: Comparative Effectiveness of Allografts, Autografts, and Conduits.

BACKGROUND: Ideal nerve repair involves tensionless direct repair, which may not be possible after resection. Bridging materials include nerve autograft, allograft, or conduit. This study aimed to perform a systematic literature review and meta-analysis to compare the meaningful recovery (MR) rates and postoperative complications following autograft, allograft, and conduit repairs in nerve gaps greater than 5 mm and less than 70 mm. A secondary aim was to perform a comparison of procedure costs. METHODS: The search was conducted in MEDLINE from January of 1980 to March of 2020, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included whether they reported nerve injury type, repair type, gap length, and outcomes for MR rates. Thirty-five studies with 1559 nerve repairs were identified. RESULTS: Overall MR for sensory and motor function was not significantly different between autograft ( n = 670) and allograft ( n = 711) across both short and long gaps. However, MR rates for autograft (81.6%) and allograft (87.1%) repairs were significantly higher compared with conduits (62.2%) ( P < 0.05) in sensory short gap repairs. Complication rates were comparable for autograft and allograft but higher for conduit with regard to pain. Analysis of costs showed that total costs for allograft repair were less than autograft in the inpatient setting and were comparable in the outpatient setting. CONCLUSIONS: Literature showed comparable rates of MR between autograft and allograft, regardless of gap length or nerve type. Furthermore, the rates of MR were lower in conduit repairs. In addition, the economic analysis performed demonstrates that allograft does not represent an increased economic burden compared with autograft.

Comparative evaluation of demineralized freeze-dried bone allograft with and without concentrated growth factor membrane in the treatment of periodontal intrabony defects: a randomized controlled clinical trial.

BACKGROUND: The current study's aim was to evaluate and compare demineralized freeze-dried bone allograft (DFDBA) with and without concentrated growth factor (CGF) membrane in the treatment of periodontal intrabony defects on both a clinical and radiographic level. METHODS: 30 stage III grade B periodontitis patients with bilateral intrabony defects were involved in the split mouth randomized controlled trial, and they received either DFDBA alone (control group) or DFDBA plus CGF membrane treatment (test group). At baseline and 6 and 12 months, the gingival index (GI), plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and gingival recession (GR) were assessed, whereas cone beam computed tomography was used to assess the bone defect height (BDH), vertical bone loss (VBL), bone defect depth (BDD), mesio-distal bone defect width (MDBDW), bucco-lingual bone defect width (BLBDW), and bone defect volume (CBCT) at baseline and 12 months. RESULTS: The radiographic measures BDH, BDD, MDBDW, BLBDW, and BDV in the test group likewise showed a higher reduction in PPD and gain in CAL than the control group. The results of the intergroup comparison showed that the test group had statistically significant differences in BDH, BDD, and MDBDW. CONCLUSION: The data show that the test group achieved better results, with greater reductions in PPD, gains in CAL, and decreases in BDH, BDD, MDBDW, BLBDW, and BDV. CLINICAL RELEVANCE: The use of concentrated growth factor in conjunction with demineralized freeze-dried bone allograft may be suggested for the treatment of periodontal intrabony defects.

Local delivery of tacrolimus using electrospun poly-ϵ-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts.

Objective.Repair of nerve gap injuries can be achieved through nerve autografting, but this approach is restricted by limited tissue supply and donor site morbidity. The use of living nerve allografts would provide an abundant tissue source, improving outcomes following peripheral nerve injury. Currently this approach is not used due to the requirement for systemic immunosuppression, to prevent donor-derived cells within the transplanted nerve causing an immune response, which is associated with severe adverse effects. The aim of this study was to develop a method for delivering immunosuppression locally, then to test its effectiveness in reducing the immune response to transplanted tissue in a rat model of nerve allograft repair.Approach.A coaxial electrospinning approach was used to produce poly-ϵ-caprolactone fibre sheets loaded with the immunosuppressant tacrolimus. The material was characterised in terms of structure and tacrolimus release, then testedin vivothrough implantation in a rat sciatic nerve allograft model with immunologically mismatched host and donor tissue.Main results.Following successful drug encapsulation, the fibre sheets showed nanofibrous structure and controlled release of tacrolimus over several weeks. Materials containing tacrolimus (and blank material controls) were implanted around the nerve graft at the time of allograft or autograft repair. The fibre sheets were well tolerated by the animals and tacrolimus release resulted in a significant reduction in lymphocyte infiltration at 3 weeks post-transplantation.Significance.These findings demonstrate proof of concept for a novel nanofibrous biomaterial-based targeted drug delivery strategy for immunosuppression in peripheral nerve allografting.

Lateral Meniscal Allograft Transplantation Provides a Chondroprotective Effect on Articular Cartilage: Quantitative 3-T Magnetic Resonance Imaging T2 Mapping.

PURPOSE: This study aimed to assess the cartilage status in patients who underwent isolated lateral meniscus allograft transplantation (MAT) using preoperative and postoperative quantitative 3-T magnetic resonance imaging T2 mapping at midterm follow-up period. METHODS: Patients who underwent lateral MAT without cartilage treatment procedures between 2010 and 2019 were assessed by quantitative magnetic resonance imaging preoperatively and postoperatively. On the sagittal section image following the center of the lateral femoral condyle, the weight-bearing area of the articular cartilage was divided into 6 segments based on the meniscal coverage area from anterior to posterior direction. The mean T2 values of each of the 6 segments were measured for 3 regions of interest: overall, deep, and superficial layers. The change in T2 values was statistically analyzed by paired t-tests. The Lysholm score was used to evaluate clinical function. RESULTS: A total of 105 patients were included in the study. The mean follow-up period was 3.2 years (range 2.0-5.4 years). Among the 6 segments, the mean T2 value showed significant improvement in the overall layer of F2 (the middle weight-bearing area of femoral condyle) and TP3 (the posterior weight-bearing area of tibia condyle) segments (P = .013 and .021, respectively) and the superficial layer of the F3 (the posterior weight-bearing area of femoral condyle) segments (P = .028). The mean T2 value of all the other segments did not show a statistically significant change. The mean Lysholm score significantly improved from 66.5 ± 15.8 to 89.3 ± 10.0 (P < .001). Overall, 73.3% and 96.2% of the patients met the minimal clinically important difference and patient acceptable symptomatic state, respectively. CONCLUSIONS: The mean T2 value of the articular cartilage of the weight-bearing area was either maintained or showed statistically significant improvement depending on the location following isolated lateral MAT. Thus, the transplanted meniscus seems to have a chondroprotective effect on the weight-bearing cartilage. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Transgenic Schwann cells overexpressing POU6F1 promote sciatic nerve regeneration within acellular nerve allografts.

Objective.Acellular nerve allograft (ANA) is an effective surgical approach used to bridge the sciatic nerve gap. The molecular regulators of post-surgical recovery are not well-known. Here, we explored the effect of transgenic Schwann cells (SCs) overexpressing POU domain class 6, transcription factor 1 (POU6F1) on sciatic nerve regeneration within ANAs. We explored the functions of POU6F1 in nerve regeneration by using a cell model of H2O2-induced SCs injury and transplanting SCs overexpressing POU6F1 into ANA to repair sciatic nerve gaps.Approach.Using RNA-seq, Protein-Protein Interaction network analysis, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we identified a highly and differentially expressed transcription factor, POU6F1, following ANA treatment of sciatic nerve gap. Expressing a high degree of connectivity, POU6F1 was predicted to play a role in peripheral nervous system myelination.Main results.To test the role of POU6F1 in nerve regeneration after ANA, we infected SCs with adeno-associated virus-POU6F1, demonstrating that POU6F1 overexpression promotes proliferation, anti-apoptosis, and migration of SCsin vitro. We also found that POU6F1 significantly upregulated JNK1/2 and c-Jun phosphorylation and that selective JNK1/2 inhibition attenuated the effects of POU6F1 on proliferation, survival, migration, and JNK1/2 and c-Jun phosphorylation. The direct interaction of POU6F1 and activated JNK1/2 was subsequently confirmed by co-immunoprecipitation. In rat sciatic nerve injury model with a 10 mm gap, we confirmed the pattern of POU6F1 upregulation and co-localization with transplanted SCs. ANAs loaded with POU6F1-overexpressing SCs demonstrated the enhanced survival of transplanted SCs, axonal regeneration, myelination, and functional motor recovery compared to the ANA group loaded by SCs-only in line within vitrofindings.Significance.This study identifies POU6F1 as a novel regulator of post-injury sciatic nerve repair, acting through JNK/c-Jun signaling in SCs to optimize therapeutic outcomes in the ANA surgical approach.