Fresh Allograft Research Articles

Fresh homograft from the recipient's explanted heart: A Colombian alternative for procuring marginal donors

Fresh homograft from the recipient's explanted heart: A Colombian alternative for procuring marginal donors

Pros and Cons of Cryopreserving Allogeneic Stem Cell Products.

The COVID-19 pandemic has precipitously changed the practice of transplanting fresh allografts. The safety measures adopted during the pandemic prompted the near-universal graft cryopreservation. However, the influence of cryopreserving allogeneic grafts on long-term transplant outcomes has emerged only in the most recent literature. In this review, the basic principles of cell cryopreservation are revised and the effects of cryopreservation on the different graft components are carefully reexamined. Finally, a literature revision on studies comparing transplant outcomes in patients receiving cryopreserved and fresh grafts is illustrated.

Fresh Versus Frozen Meniscal Allograft Transplant: Revisit or Redundant? A Systematic Review

Background: Fresh-frozen allografts are the current standard in meniscal allograft transplant (MAT) surgery, due to their availability, ease of preservation, and affordability. However, fresh-frozen grafts are associated with several clinical challenges such as graft shrinkage and extrusion, among many others. Purpose: To present the current knowledge on the use of fresh meniscal allografts, presenting whether benefits associated with fresh grafts provide sufficient evidence to support their use in clinical practice. Study Design: Systematic review; Level of evidence, 5. Methods: A comprehensive search was conducted with keywords listed below. After an initial screening on title and abstract, full-text articles were assessed with the inclusion criteria. Results: A total of 78 studies matched the inclusion criteria. Literature and preclinical studies indicated that fresh meniscal allografts are beneficial for maintaining mechanical properties, graft ultrastructure, and matrix metabolism due to the presence of viable cells. Therefore, fresh allografts may address common complications associated with fresh-frozen MAT. To overcome challenges associated with both fresh-frozen and fresh allografts, a group has studied treating fresh-frozen allografts with a cell-based injection therapy. Conclusion: Fresh meniscal allografts pose several challenges including limited availability, demanding preservation procedures, and high costs. Although the role of viable cells within meniscal allografts remains controversial, these cells may be vital for maintaining tissue properties.

Clinical impact of cryopreservation of allogeneic hematopoietic cell grafts during the onset of the COVID-19 pandemic

AbstractAt the onset of the COVID-19 pandemic, the National Marrow Donor Program mandated the cryopreservation of hematopoietic cell grafts from volunteer unrelated donors because of numerous patient and donor safety concerns and logistical hurdles. Using the Center for International Blood and Marrow Transplant Research outcomes database, we report the impact of cryopreservation on overall survival (OS) and other outcomes within 1 year after hematopoietic cell transplantation (HCT). We analyzed 1543 recipients of cryopreserved allografts receiving HCT at US centers during the first 6 months of the pandemic and compared them with 2499 recipients of fresh allografts during a 6-month period in 2019. On multivariable regression analysis, we observed no difference in the OS (P = .09), nonrelapse mortality (P = .89), graft-versus-host disease (GVHD), or GVHD- and relapse-free survival (P = .58) in recipients of cryopreserved vs fresh allografts. Disease-free survival (DFS) was lower in the cryopreserved allograft recipients (P = .006) because of a higher risk of relapse (P = .01) compared with the fresh allograft recipients. Primary graft failure was higher (P = .01), and the risk of chronic GVHD was lower (P = .001) with cryopreservation compared with fresh grafts. In conclusion, although there was no negative impact of cryopreservation on OS, relapse was higher, and DFS was lower than that with no cryopreservation. Fresh grafts are recommended as the pandemic-related logistical hurdles resolve. Cryopreservation should be considered an option for patients when fresh grafts are not feasible.

Mechanical Properties of Fresh, Frozen and Vitrified Articular Cartilage.

Osteochondral allograft transplantations are typically used to treat focal articular cartilage injuries where the damaged cartilage is replaced with fresh cadaveric donor grafts. Despite the notable success rate of this procedure, it is limited by fresh donor tissue availability which can only be stored for approximately 28days after harvest. Vitrification, a form of cryopreservation, can extend the storage time of cartilage. Although it has shown to preserve chondrocyte viability, its effect on the mechanical properties of the tissue has not been thoroughly investigated. Therefore, in this study, the mechanical properties of fresh, frozen, and vitrified articular cartilage were evaluated through unconfined compression testing. Results showed that the peak modulus, equilibrium modulus, and relaxation time constants of the vitrified and control samples (tested one day after harvest) were similar and higher than the fresh (tested 21days after harvest) and frozen samples. This demonstrated that vitrification does not adversely affect the mechanical properties of cartilage and can be used as an alternative to fresh allografts which are limited by storage time. The fresh samples also had inferior mechanical properties compared to the control samples suggesting that vitrified allografts could potentially improve clinical outcomes in addition to increasing donor tissue availability.

Fresh arterial allograft as a replacement for an infected common femoral prosthetic graft and recurrent false aneurysm.

Replacing an infected vascular prosthetic conduit with an allograft is a possible solution of this complication given the low recurrence of infection. It is most commonly utilized for cases where the use of autologous tissue is not an option. We present the case of a 70-year-old patient who had undergone repeated vascular reconstructions in the right lower limb. He was admitted to our department due to a progressively growing mass in the right groin and subsequently placed on the waiting list for a fresh allograft. The patient had the infected false aneurysm and prosthetic material of the femoral bifurcation replaced with an arterial allograft. The previous femoral popliteal autovenous bypass graft was reimplanted into the allograft. There were signs of sepsis during the operation; however, the blood culture was negative. Cultures from neither the wound nor the drain revealed the presence of any bacteria. The patient was discharged on the seventh post-operative day with prophylactic antibiotics. An early followup confirmed that there were no signs of recurrent infection and that the reconstruction remained patent. Seven and half months after the surgery, the femoral popliteal bypass graft became occluded and a conservative approach was chosen. A small thrombosed false aneurysm of the graft was revealed two years after the surgery due to transient non-compliance of the patient to immunosuppression therapy. It was treated conservatively. Two and a half years after the surgery, the allograft still remains open and the limb is preserved.

Cryopreserved versus fresh peripheral blood allogeneic stem cell transplantation outcomes in patients receiving post-transplant cyclophosphamide for graft-versus-host prophylaxis during the COVID-19 pandemic: a single center experience.

Cryopreservation of grafts is not common practice in allogeneic hematopoietic stem cell transplant (HSCT) recipients. However, our center had to use cryopreserved cells for allogeneic HSCT during the COVID-19 pandemic to avoid delays in transplantation due to uncertainty regarding patient and donor exposures. We retrospectively evaluated post-transplant engraftment and survival outcomes of adult patients who received cryopreserved versus fresh allografts during the COVID-19 pandemic. Fifty-five patients with hematologic malignancies received either cryopreserved (n = 34) or fresh (n = 21) allogeneic HSCT using peripheral blood stem cells between January 2020 and December 2020. At a median follow-up time of 15months, cryopreserved allograft recipients had significantly lower overall survival (OS) (p = 0.02). They also experienced significantly delayed neutrophil (p = 0.01) and platelet engraftments (p < 0.0001), as well as higher red blood cell transfusion-dependence after day + 60 (67.6% vs. 28.6%; p = 0.01). Significantly more cryopreserved allograft recipients received donor lymphocyte infusion than fresh allograft recipients (35.3% vs. 4.8%, p = 0.01). Neither relapse-free survival nor non-relapse mortality differed significantly between the two groups. Cryopreservation of allografts in combination with post-transplant cyclophosphamide may negatively affect engraftment and OS outcomes in HSCT recipients.

Effect of vitrification on mechanical properties of porcine articular cartilage.

Articular cartilage (AC) injuries do not heal primarily and large lesions progress to degenerative osteoarthritis. Osteochondral allograft transplantation is an effective surgical treatment but is limited by the lack of donor tissue availability. Fresh allografts can be stored hypothermically up to 28–45 days after which the tissue is no longer viable for transplantation. Vitrification is a method of cryopreservation with the potential to extend the storage time of AC. A specific protocol has been demonstrated to preserve high chondrocyte viability; however, its effect on various mechanical properties of the extracellular matrix (ECM) remains unknown and is the focus of this initial study. Porcine AC was subject to a defined vitrification protocol, using fresh and frozen samples as positive and negative controls, respectively; n = 20 for all three groups. Unconfined compression testing was used to assess mechanical properties of the tissue under rapid load, stress relaxation, and equilibrium conditions. The stress relaxation time constants (modeled with a 2-term Prony series) and were significantly lower for frozen (p = 0.014, p < 0.001) and vitrified (p = 0.009, p = 0.003) tissue compared to fresh, with no differences between frozen and vitrified samples (p = 0.848 and 0.105 for and , respectively). These values indicate that frozen and vitrified samples relaxed more rapidly than fresh, which may suggest altered matrix composition and permeability post-treatment. These results represent the initial study in our experimental path to evaluate differences in mechanical properties of vitrified tissues.

Humeral Head Osteochondral Allograft Reconstruction for Chronic Locked Posterior Glenohumeral Dislocation With Large Reverse Hill–Sachs Defect

Background: Locked posterior glenohumeral dislocations are a rare but often missed injury when it occurs. In these dislocations, patients may have a reverse Hill–Sachs lesion, which are associated with high rates of recurrent posterior glenohumeral instability. Open reduction with allograft reconstruction to reconstruct the defect can be used to treat chronic locked posterior glenohumeral dislocations. Indications: Osteochondral allograft reconstruction is indicated when patients have a large defect affecting less than 50% of the articular surface and if the humeral head has been dislocated for less than 6 months. Technique Description: With the patient in beach chair position, exposure is obtained through deltopectoral approach. An open reduction is performed, and the defect is debrided down to healthy bleeding bone. The defect is templated, and the allograft is harvested and prepared. The allograft is securely fixed using cannulated cancellous screws. The patient undergoes a postoperative rehabilitation protocol. Results: There have been several case series following allograft reconstruction for locked posterior dislocations that have demonstrated good results. Riff et al found favorable results in his series of 20 patients with isolated humeral head lesions, with significant improvement in patient-outcome measures. There are several potential complications though. A systematic review by Saltzman et al found allograft resorption to occur in 36% and glenohumeral arthritic changes to occur in 35% with frozen allografts. These rates appear to be improved with fresh allografts. Discussion/Conclusion: In conclusion, osteochondral allograft is an effective surgical treatment for large Hill–Sachs defects in chronic locked posterior dislocations.

Nerve regeneration in rat peripheral nerve allografts: An assessment of the role of endogenous neurotrophic factors in nerve cryopreservation and regeneration.

Peripheral nerve injury is a common clinical problem that often leads to significant functional impairment or even complete paralysis. Allograft has been proposed as a potential repair strategy for peripheral nerve injuries. Furthermore, peripheral nerve cryopreservation may result in nearly unlimited supply of grafts. However, the concentration of neurotrophic factors secreted by Schwann cells (SCs) in the local micro-environment after transplantation may not be sufficient for the survival of neuronal soma and axonal regeneration. Here, we investigated the effect of endogenous neurotrophic factors (ENTFs) on nerve regeneration in rats after the allograft of a cryopreserved sciatic nerve. ENTFs were highly expressed in the sciatic nerves pretreated for 14 days. Although the number of surviving cells in the sciatic nerves and their immunogenicity were low in the 14-day group after 4weeks of cryopreservation, they continued to express high levels of ENTFs in vitro. At 1 week postoperation, the 14-day Allo group showed low plasma levels of interleukin-2, interferon-γ and tumour necrosis factor-alpha and low cellular immune response. At 20 weeks postoperation, nerve regeneration and functional recovery in the 14-day Allo group was similar to that in the fresh isograft group but better than that in the cryopreserved-fresh allograft and fresh allograft groups. Thus, ENTFs were induced in vitro after pretreatment of the sciatic nerve. Following cryopreservation, the sciatic nerves with high levels of ENTFs continued to express high levels of ENTFs in vitro. The immune response after allograft was weak, which promoted recipient nerve regeneration.

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production.

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

In response to the widespread COVID-19 pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear. In this study, we compared outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 and 60 consecutive patients who received fresh allografts before the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment and graft failure (GF), and secondary outcomes were overall survival (OS), relapse-free survival (RFS) and nonrelapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved and prospectively collected fresh apheresis samples. Compared with recipients of fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced-intensity conditioning (RIC) allo-HCT, with a median time to engraftment of 24 days versus 18 days (P = .01) for neutrophils and 27 days versus 18 days (P = .069) for platelets. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) versus only 1 of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid, and T cell donor chimerism at 1 month. OS and RFS were inferior for cryopreserved graft recipients (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.00 to 4.67) and HR, 1.90; 95% CI, 0.95 to 3.79, respectively. Using an extended immunophenotype analysis, we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both a decrease in total cell viability and a significantly reduced absolute number of natural killer cells (CD3−CD56+) in the cryopreserved apheresis samples. In this single-institution study, we found delayed engraftment and a trend toward clinical inferiority of cryopreserved allografts compared with fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.

Mega-OATS of the knee without specialised instrumentation: a low-cost option for large cartilage defects in a resource-restrained environment

BACKGROUND: A 26-year-old patient presented to a specialised knee clinic in a public hospital with ongoing pain after having sustained a soccer injury six years prior. A large osteochondral defect of the distal medial femoral condyle was diagnosed. Due to resource limitations, fresh allograft or a large osteochondral autograft transplantation system (Mega-OATS) workbench was unavailable. CASE REPORT: A Mega-OATS cartilage transplantation was done, using the patient's posteromedial femoral condyle as donor tissue, and transplanted to the defect in the distal femoral condyle, a technique that has been well documented and followed up. At six weeks postoperatively, an MRI showed early incorporation of the graft tissue. Clinical outcomes were excellent at one year follow-up with the EQ-5D 5L score 11111, the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS) 100%, and the Lysholm score also 100%. Radiographs at one year confirmed an unchanged graft position and showed no signs of osteoarthritis. DISCUSSION: Large osteochondral lesions in the knee (&gt; 4 cm2) are challenging to treat, and the most commonly used modalities are fresh osteochondral allograft (OCA) or autologous chondrocyte implantation (ACI). Mega-OATS of the knee has previously been described but is not commonly used due to the requirement of a specialised and expensive workbench, and fear of morbidity at the donor site. CONCLUSION: Mega-OATS of the knee is possible without a specialised workbench or tools and had good clinical outcomes at two-year follow-up of the patient. Level of evidence: Level 5

Intra-Articular Synovial Fluid With Hematoma After Ankle Fracture Promotes Cartilage Damage In Vitro Partially Attenuated by Anti-Inflammatory Agents.

Intra-articular ankle fracture (IAF) causes posttraumatic osteoarthritis (PTOA), but the exact mechanism is unknown. Proinflammatory mediators have been shown to be present in the synovial fluid fracture hematoma (SFFH) but have not been linked to cartilage damage. The purpose of this study was to determine if the SFFH causes cartilage damage and whether this damage can be attenuated by commercially available therapeutic agents. Synovial fluid was obtained from 54 IAFs and cultured with cartilage discs from the dome of fresh allograft human tali and randomly assigned to one of the following groups: (A) control-media only, (B) SFFH from days 0 to 2 after fracture, (C) SFFH from days 3 to 9, (D) SFFH from days 10 to 14, (E) group B + interleukin 1 receptor antagonist (IL-1Ra), and (F) group B + doxycycline. The cartilage discs underwent histological evaluation for cell survival and cartilage matrix components. The spent media were analyzed for inflammatory mediators. Cartilage discs cultured with SFFH in groups B, C, and D demonstrated significantly increased production of cytokines, metalloproteinases (MMPs), and extracellular matrix breakdown products. Safranin O staining was significantly decreased in group B. The negative effects on cartilage were partially attenuated with the addition of either IL-1RA or doxycycline. There was no difference in chondrocyte survival among the groups. Exposure of uninjured cartilage to IAF SFFH caused activation of cartilage damage pathways evident through cartilage disc secretion of inflammatory cytokines, MMPs, and cartilage matrix fragments. The addition of IL-1Ra or doxycycline to SFFH culture partially attenuated this response. IAFs create an adverse intra-articular environment consisting of significantly increased levels of inflammatory cytokines and MMPs able to damage cartilage throughout the joint. These data suggest that the acute addition of specific inflammatory inhibitors may decrease the levels of these proinflammatory mediators.

Histological and Inflammatory Cytokine Analysis of Osteochondral Lesions of the Talus After Failed Microfracture: Comparison With Fresh Allograft Controls.

Background:The most common first-line treatment of osteochondral lesions of the talus (OLTs) is microfracture. Although many patients do well with this procedure, a number fail and require reoperation. The mechanism of failure of microfracture is unknown, and to our knowledge there has been no research characterizing failed microfracture regarding histological and inflammatory makeup of these lesions that may contribute to failure.Purpose:To characterize the structural and biochemical makeup of failed microfracture lesions.Study Design:Case series; Level of evidence, 4.Methods:Specimens from 8 consecutive patients with symptomatic OLTs after microfracture who later underwent fresh osteochondral allograft transplantation were analyzed. For each patient, the failed microfracture specimen and a portion of the fresh allograft replacement tissue were collected. The allograft served as a control. Histology of the failed microfracture and the allograft replacement was scored using the Osteoarthritis Research Society International (OARSI) system. Surface roughness was also compared. In addition, tissue culture supernatants were analyzed for 16 secreted cytokines and matrix metalloproteinases (MMPs) responsible for inflammation, pain, cartilage damage, and chondrocyte death.Results:The OARSI grade, stage, and total score as well as surface smoothness were significantly worse in the failed microfracture sample, indicating better cartilage and bone morphology for the allografts compared with the failed microfracture lesions. Analyzed cytokines and MMPs were significantly elevated in the microfracture tissue culture supernatants when compared with fresh osteochondral tissue supernatants.Conclusion:These data demonstrate a significantly rougher cartilage surface, cartilage and subchondral bone histology that more closely resembles osteoarthritis, and elevated inflammatory cytokines and MMPs responsible for pain, inflammation, cartilage damage, and chondrocyte death when compared with fresh osteochondral allografts used as controls.

Combined Cortico-cancellous and cancellous fresh paternal allograft in defect post resection of benign bone tumors of long bones in children, review of literatures with two cases study

We study the use of paternal fresh allograft in pediatric massive bony loss (post benign bone tumor resection) with a graft type of combined Cortico-cancellous and cancellous bone, with a good result of rapid and complete union with no recurrence with in 2years of follow up, with no any sign of local or systemic rejection. Study of 2 patients, one of an osteoblastoma in female of 9 years old in shaft femur and the second case was an aneurysmal bone cyst (ABC) in male of 11 years old in distal third of fibula where in both do enbloc resection for a big bony lesions in such young age group, the defect was 8cm in the female and 9 cm in male case. We reconstruct these defects by the fresh non-frozen paternal allograft which still not widely used method and we add the use of Combined Cortico-cancellous and cancellous bone graft of iliac crest area which was not used or mentioned before in literatures and we do internal fixation in both and we wash the graft 2 times pre and post application in the gap with a normal saline for each case, follow up by monthly x-ray films till healing. Was conclusive and more than expected regarding healing rate and union which was 6month in female case and 5 month in male and no complication in such big bony graft mass. In Followed up of 2 years no recurrance was seen and both donors and recipients without any disability nor morbidity.

The Effect of Donor Graft Cryopreservation on Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center for International Blood and Marrow Transplant Research Analysis. Implications during the COVID-19 Pandemic

The COVID-19 pandemic has resulted in the increased use of cryopreserved grafts for allogeneic hematopoietic cell transplantation (HCT). However, information about the effect of cryopreservation on outcomes for patients receiving allogeneic donor grafts is limited. We evaluated outcomes of HCT recipients who received either fresh or cryopreserved allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) grafts reported to the Center for International Blood and Marrow Transplant Research. A total of 7397 patients were included in the analysis. Recipients of cryopreserved graft were divided into 3 cohorts based on graft source: HLA-matched related PBSC donors (n=1051), matched unrelated PBSC donors (n=678), and matched related or unrelated BM donors (n=154). These patients were propensity score matched with 5514 patients who received fresh allografts. The primary endpoint was engraftment. Multivariate analyses showed no significant increased risk of delayed engraftment, relapse, nonrelapse mortality (NRM), or survival with cryopreservation of BM grafts. In contrast, cryopreservation of related donor PBSC grafts was associated with decreased platelet recovery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68 to 0.78; P < .001) and an increased risk of grade II-IV (HR, 1.27; 95% CI, 1.09 to 1.48; P=.002) and grade III-IV (HR, 1.48; 95% CI, 1.19 to 1.84; P < .001) acute graft-versus-host disease. Cryopreservation of unrelated PBSC grafts was associated with delayed engraftment of neutrophils (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001) and platelets (HR, 0.61; 95% CI, 0.56 to 0.66; P < .001) as well as an increased risk of NRM (HR, 1.4; 95% CI, 1.18 to 1.66; P < .001) and relapse (HR, 1.32; 95% CI, 1.11 to 1.58; P=.002) and decreased progression-free survival (HR, 1.36; 95% CI, 1.20 to 1.55; P < .001) and overall survival (OS) (HR, 1.38; 95% CI, 1.22 to 1.58; P < .001). Reasons for cryopreservation were not routinely collected; however, in a subset of unrelated donor HCT recipients, the reason was typically a change in patient condition. Products cryopreserved for patient reasons were significantly associated with inferior OS in multivariate analysis (HR, 0.65; 95% CI, 0.44 to 0.96; P=.029). We conclude that cryopreservation is associated with slower engraftment of PBSC grafts, which may be associated with inferior transplantation outcomes in some patient populations. However, the small numbers in the cryopreserved BM cohort and the lack of information on the reason for cryopreservation in all patients suggests that these data should be interpreted with caution, particularly in the context of the risks associated with unexpected loss of a graft during the pandemic. Future analyses addressing outcomes when cryopreservation is universally applied are urgently required.

Use of fresh osteochondral allograft in repair of distal femur after trauma

Preserving the ability to maintain an active lifestyle is a major concern in the reconstruction of the knee in young patients. For the healthy individual who desires to maintain a relatively active lifestyle, fresh osteochondral allografts may serve as an alternative to total joint reconstruction. The use of fresh allografts is primarily indicated in the patient suffering from a traumatic loss of articular segments, who is too young or active for arthroplasty. In addition, fresh osteochondral allografts have a number of advantages over arthroplasty such as providing surgeons with a source of large grafts that can be fitted to replace osteochondral defects and cover the majority or entirety of articular surfaces without any donor site morbidity. In this case, a young, active patient lost a 7 x 8 cm portion of their distal femur, including a large portion of the articulating surface. Using a fresh osteochondral allograft, harvested within 24 hours of donor death, a segment was fitted to match bony apposition, articular congruity, and congruity with the femoral notch and affixed with four partially threaded cancellous screws. Joint function was restored with the allograft in place, allowing the patient to delay the need for a total joint replacement.

Outcomes of talar osteochondral and transchondral lesions using an evidence-based algorithmic approach based on size, location and subchondral plate integrity: a 10-year study on 204 lesions

Objectives:Treatments outcomes for articular lesions of the talus are variable based on size. MRI has been used to assess size and location, and base treatment. We prospectively analyzed talar lesions and the outcomes of surgical procedures based on lesion size, which are typically measured two-dimensionally, intact cartilage/subchondral plate and activity level. We propose following a treatment algorithm will yield favorable results and outcomes.Methods:Over a ten-year period, transchondral and osteochondral lesions of the talus were measured tri-dimensionally on pre-operative MRI, location noted based on a nine-region grid pattern of the talar dome, and patients’ activity level documented. Procedures were performed based on lesion size, integrity of cartilage and lesion location. They were assessed with pre- and post-operative AOFAS scores, post-operative Roles Maudsley score and time to return to activity. Lesions below 125 mm³ were treated with microfracture or retrograde drilling, lesions less than 1500 mm³ were treated with autogenous bone graft, and larger lesions were treated with fresh allograft.Results:204 talar lesions were analyzed. The following surgeries were performed: arthroscopy with microfracture or retrograde drilling (with or without bone graft) N =159, arthrotomy (with or without osteotomy) with autogenous bone graft N = 60, and fresh allograft with osteotomy N =7. The average follow-up post-index surgery was 82.53± 34.62 (range 24-132) months for the entire cohort. The average time to return to activity was 7.93 ± 5.00 (range 2-36) months. The average pre-AOFAS score was 76.44 ± 10.98 (range 52-86) and average post-AOFAS score was 96.12 ± 3.46 (range 81-100), P=.0001. Post-surgery RM score was 1.28 ± 0.49 (range 1-3). There were no differences in outcomes based on lesion size.Conclusion:Similar outcomes were able to be achieved regardless of talar lesion size using the treatment algorithm.Clinicians should consider using three-dimensional measurements when determining the best treatment approach to talar lesions.Microfracture, while successful for certain talar lesions, may not have a role for larger lesions. Other techniques such as retrograde drilling, autogenous bone grafting and allograft can yield good results, along with microfracture when used appropriately based on lesion size.

Intraarticular Inflammation and Catabolic Markers in Femoroacetabular Impingement during Progression of Disease -comparison between early and late stage disease-

Objectives:Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of osteoarthritis hips (OA). Inflammation is thought to be one of the main initiators of hip OA, yet little is known about the location and progression of intraarticular inflammation in FAI hips. The aim of this study is to characterize inflammation and catabolic markers in the early and late stage of FAI hips in patients with symptomatic Cam FAI.Methods:Head-neck cartilage, acetabular cartilage, and synovial samples were obtained from 30 patients undergoing hip surgery. Fifteen patients had a diagnosis of symptomatic Cam FAI (early FAI-symptomatic FAI) and 15 presented with advanced OA secondary to Cam FAI (late FAI/secondary OA). Control cartilage samples were procured from the head-neck junction of 7 osteochondral fresh allografts from healthy young-adult donors (control). Radiographically, the α-angle was utilized to confirm hip impingement and Tönnis grade was used to define pre-OA (Tönnis grade 0-1) and advanced OA (Tönnis grade >2). Safranin O stained sections were used to assess cartilage degeneration using the Mankin score. Immunostaining of IL-1β, MMP-13, ADAMTS-4, type II collagen (COL2), and the NITEGE aggrecan neoepitote was performed to evaluate inflammation and catabolic markers. Quantification of immunopositive cells was performed and one-way analysis of variance with Tukey’s post hoc test was applied to analyze differences between groups.Results:Characteristics of the study participants are presented in Table 1. Cartilage from the impingement zone (head-neck and acetabulum) of hips with early and late FAI showed microscopic osteoarthritic degenerative changes. Compared to control, head-neck cartilage from early and late stage FAI hips highly expressed inflammatory and catabolic markers IL-1β (69.7±18.1, 72.5±13.2 vs 20.2±4.9), MMP-13 (79.6±12.6, 71.4±18.8 vs 25.3±9.5), ADAMTS-4 (83.9±12.2, 82.6±12.5 vs 24.3±11.1), NITEGE (89.7±7.7, 95.7±4.7 vs 39.8±20.5) (p<0.05). Expression for COL2 was similar among groups (93.6±3.9, 92.5±5.8 vs 95.4±6.4, p=0.4892). Finally, percent of immunopositive cells for IL-1β, MMP-13, ADAMTS-4, and ACAN were positively correlated with Mankin score (r=0.52-0.75; p<0.001). The percentage of immunopositive cells present in acetabular cartilage was similar in both early and late FAI (IL-1β: 83.3 ± 24.8, 80.7 ± 15.6, 80.9 ± 26.3, p = 0.9571; MMP-13: 94.3 ± 9.7, 85.2 ± 12.3, 93.3 ± 10.3, p = 0.0653; ADAMTS-4: 98.5 ± 2.3, 98.4 ± 3.4, 99.2 ± 3.0, p = 0.6997, COL2: 99.8 ± 0.7, 99.7 ± 1.1, 98.6 ± 3.6, p = 0.3830). Additionally, inflammatory and catabolic markers were secreted to the ECM (extracellular matrix) in late FAI but not in early FAI. (Figure 1) Synovitis was minimal in early FAI but severe in late FAI. The average synovitis score was lower in early FAI than late FAI (2.5 ± 1.7, 4.4 ± 1.6; p=0.0086). Lower IL-1β expression levels were noted in synovium from early FAI compared to late FAI (p=0.001).Conclusion:Osteoarthritic degenerative changes, inflammation and catabolic markers are evident in the cartilage from the head-neck and acetabulum (impingement zone) in patients with hip FAI morphology during early and late stage disease. In late disease, increase expression of these markers are also observed in the ECM. Severe synovitis, however, was only evident in late stage disease. This study defines joint specific location and timing of inflammation relative to the disease process, suggesting the impingement area is a potential mediator of inflammation and joint degeneration during disease progression.