Introduction

The purpose of this study was to examine trends in patient characteristics and clinical outcomes that occur with age as a statistical variable when performing autologous osteochondral transplantation (AOT) for the treatment of osteochondral lesions of the talus (OLT).

Autologous osteochondral transplantation (AOT) is an effective treatment for large Osteochondral Lesions of the Talus (OLT), however little is reported on an athletic population, who are likely to place higher demands on the reconstruction. The aim is to report the outcomes of large OLT (>150mm²) within an athletic population. The study population was limited to professional or amateur athletes (Tegner score >6) with an OLT of size 150mm² or greater. The surgical intervention was AOT with a donor site from the lateral femoral condyle. Clinical outcomes at a minimum of 24 months included Return to Sport, VAS and FAOS Scores. In addition, graft incorporation was evaluated by MRI using MOCART scores at 12 months post-surgery. 38 athletes including 11 professional athletes were assessed. Mean follow-up was 46 months. Mean lesion size was 249mm². 33 patients returned to sport at their previous level and one did not return to sport (mean return to play 8.2 months). Visual analogue scores improved from 4.53 pre-operatively to 0.63 post-operatively (p=0.002). FAOS Scores improved significantly in all domains (p< 0.001). Two patients developed knee donor site pain, and both had three osteochondral plugs harvested. Univariant analysis demonstrated no association between pre-operative patient or lesion characteristics and ability to return to sport. However, there was a strong correlation between MOCART scores and ability to return to sport (AUC=0.89). Our study suggests that AOT is a viable option in the management of large osteochondral talar defects in an athletic population, with favourable return to sport levels, patient satisfaction, and FAOS/VAS scores. The ability to return to sport is predicated upon good graft incorporation and further research is required to optimise this technique. Our data also suggests that patients should be aware of the increased risk of developing knee donor site pain when three osteochondral plugs are harvested.

Introduction

Osteochondral lesions (OCLs) of the talus are a challenging and increasingly recognized problem in chronic ankle pain. Many novel techniques exist to attempt to treat this challenging entity. Difficulties associated with treating OCLs include lesion location, size, chronicity, and problems associated with potential graft harvest sites. Matrix associated stem cell transplantation (MAST) is one such treatment described for larger lesions >15mm2 or failed alternative therapies. This cohort study describes a medium-term review of the outcomes of talar lesions treated with MAST.

Abstract

Abstract

The extracellular matrix (ECM)-based biomaterials provide a platform to mimic the disc microenvironment in facilitating stem cell transplantation for tissue regeneration. However, little is known about in vitro preconditioning human umbilical cord Wharton Jelly-derived mesenchymal stem cells (MSCs) on 3D hyaluronic acid (HA)/type II collagen (COLII) hydrogel for nucleus pulposus (NP) phenotype and pain modulation.

We developed a tuneable 3D HA/COLII by fabricating HA/COLII hydrogel at 2 mg/ml COLII and various weight ratios of HA:COLII, 1:9 and 4.5:9. The hydrogel was characterized for degradability, stability, and swelling capacity. The viability of hWJ-MSC encapsulated on hydrogel supplemented with TGF-β3 was assessed. The implantation of HA/COLII hydrogel was done in surgically induced disc injury model of pain in the rat tail. The general health status in rats was monitored. The nociceptive behaviour in rats was performed for mechanical allodynia using von Frey test.

The HA/COLII 4.5:9 hydrogel showed higher swelling capacity than weight ratio 1:9, suggesting that a higher amount of HA can absorb a large amount of water. Both HA/COLII 4.5:9 and 1:9 hydrogel formulations had a similar degradation profile, stable to the hydrolytic process. The hWJ-MSC-encapsulated on hydrogel marked higher cell viability with round morphology shape of cells in vitro. The surgically induced disc injury in the rat tail evoked mechanical allodynia, without affecting general health status in rats. The implantation of HA/COLII 1:9 hydrogel was observed to slightly alleviate injury-induced mechanical allodynia.

Fine-tuning HA/COLII-based hydrogel provides the optimal swelling capacity, stability, degradability, and non-cytotoxic, mimicking the 3D NP niche in guiding hWJ-MSCs towards NP phenotype. The HA/COLII hydrogel could be employed as an advanced cell delivery system in facilitating stem cell transplantation for intervertebral disc regeneration targeting pain.

Aims

Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds.

In this study, we aimed to investigate tibiofemoral and allograft loading parameters after OCA transplantation using tibial plateau shell grafts to characterize the clinically relevant biomechanics that may influence joint kinematics and OCA osseointegration after transplantation. The study was designed to test the hypothesis that there are significant changes in joint loading after tibial plateau OCA transplantation that may require unique post-operative rehabilitation regimens in patients to restore balance in the knee joint.

Fresh-frozen cadaveric knees (n=6) were thawed and mounted onto a 6 DOF KUKA robot. Specimens were size matched to +2 mm for the medial-to-lateral width of the medial tibial hemiplateaus. Three specimens served as allograft recipient knees and three served as donor knees. Recipient knees were first tested in their native state and then tested with size-matched medial tibial hemiplateau shell grafts (n=3) prepared from the donor knees using custom-cut tab-in-slot and subchondral drilling techniques. Tekscan sensors were placed in the joint spaces to evaluate the loading conditions under 90N biaxial loading at full extension of the knee before and after graft placement. The I-Scan system used in conjunction analyzed the total force, pressure distribution, peak pressure, and center of force within the joint space.

Data demonstrated significant difference (p<0.05) in joint space loading after graft implantation compared to controls in both lateral and medial tibial plateaus. The I-Scan pressure mapping system displayed changes in femoral condylar contact points as well.

The results demonstrated that joint space loading was significantly different (p<0.05) between all preoperative and postoperative cadaveric specimens. Despite the best efforts to size match grafts, slight differences in the host's joint geometry resulted in shifts of contact areas between the tibial plateau and femoral condyle therefore causing either an increase or decrease in pressure measured by the sensor. This concludes that accuracy in graft size matching is extremely important to restoring close to normal loading across the joint and this can be further ensured through postoperative care customized to the patient after OCA surgery.

Many factors have been reported to affect the functional survival of OCA transplants, including chondrocyte viability at time of transplantation, rate and extent of allograft bone integration, transplantation techniques, and postoperative rehabilitation protocols and adherence. The objective of this study was to determine the optimal subchondral bone drilling technique by evaluating the effects of hole diameter on the material properties of OCAs while also considering total surface area for potential biologic benefits for cell and vascular ingrowth.

Using allograft tissues that would be otherwise discarded in combination with deidentified diagnostic imaging (MRI and CT), a model of a large shell osteochondral allograft was recreated using LS-PrePost and FEBio based on clinically relevant elastic material properties for cortical bone, trabecular bone, cartilage, and hole ingrowth tissue. The 0.8 mesh size model consisted of 4 mm trabecular bone, 4 mm cortical bone, and 3 mm cartilage sections that summed to a cross-sectional area of 1600 mm2 (40 mm x 40 mm). Holes were modeled to be 4mm deep in relation to clinical practice where holes are drilled from the deep margin of subchondral trabecular bone to the cortical subchondral bone plate. To test the biomechanic variations between drill hole sizes, models with hole sizes pertinent to standard-of-care commercially available orthopaedic drill sizes of 1.1mm, 2.4 mm, or 4.0 mm holes were loaded across the top surface over a one second duration and evaluated for effective stress, effective strain, 1st principal strain, and 3rd principal strain in compressive conditions.

Results measured effective stress and strain and 1st and 3rd principal strain increased with hole depth.

The results of the present FEA modeling study indicate that the larger 4.0 mm diameter holes were associated with greater stresses and strains within OCA shell graft, which may render the allograft at higher risk for mechanical failure. Based on these initial results, the smaller diameter 2.4 mm and 1.1 mm holes will be further investigated to determine optimal number, configuration, and depth of subchondral drilling for OCA preparation for transplantation

Aims

The aim of this retrospective study was to determine if there are differences in short-term clinical outcomes among four different types of matrix-associated autologous chondrocyte transplantation (MACT).

Abstract

Abstract

Background

The meniscal deficient knee often exists in the setting of associated pathology including instability, malalignment and chondral injury. Meniscal allograft transplantation (MAT) is established to be a reliable option in restoring function and treating symptoms. The aim of this study was to establish the role of MAT as part of a staged approach to treatment of the previously menisectomised knee.

Cutting rodent's bone ends and irrigation of the medullary canal is the common method used for cells collection in allogenic transplantation, however it does not yield sufficient cells for autologous transplantation. The aim of this experiment was to establish and validate a method for bone marrow collection for autologous MSCs transplantation. Two collection methods were examined: 1) Transection of the bone ends and irrigation of the medullary canal, 2) Trephining of the bone with a hypodermic needle without aspiration. Then cell harvesting was compared in the idealised laboratory situation and under simulated surgery.

First, two lower limbs were harvested from the same rat cadaver for comparison, bone marrow in one limb was collected by cutting the femoral head and the distal tibia and irrigation of the canal through drilled holes at the distal end of the femur and proximal end of the tibia. Other limb, hypodermic needle was used as a trephining tool into the medullary canal multiple times without applying negative pressure and rinsed from inside and outside. Second, bone marrow was harvested from another rat's cadaver in the surgery room to simulate the conditions needed for autologous transplantation.

The number of cells from irrigation method was 1.28*106 cells, whereas that from trephining method reached 17*106. The number cells from the bone marrow harvested in the surgery room was found 29.6*106. We report a novel technique for harvesting cells for autologous cell therapy from only one limb. A significantly larger number of cells from bone marrow could be collected using the needle trephining method. There is no negative effect on the viability of cells after bone marrow harvesting in the surgery room.

Aims

The aim of this study was to report the outcome of femoral condylar fresh osteochondral allografts (FOCA) with concomitant realignment osteotomy with a focus on graft survivorship, complications, reoperation, and function.

Osteochondral lesions (OCLs) of the talus are a challenging and increasingly recognized problem in chronic ankle pain. Many novel techniques exist to attempt to treat this challenging entity. Difficulties associated with treating OCLs include lesion location, size, chronicity and problems associated with potential graft harvest sites. Matrix associated stem cell transplantation (MAST) is one such treatment described for larger lesions >15mm² or failed alternative therapies. This cohort study describes a 5 year review of the outcomes of talar lesions treated with MAST. A review of all patients treated with MAST by a single surgeon was conducted. Pre-operative radiographs, MRIs and FAOS outcome questionnaire scores were conducted. Intraoperative classification was conducted to correlate with imaging. Post-operative outcomes included FAOS scores, return to sport, revision surgery/failure of treatment and progression to arthritis/fusion surgery. 32 patients were identified in this cohort. There were 10 females, 22 males, with an average age of 35. 01. 73% had returned and continued playing active sport. 23 patients underwent MAST in the setting of a failed previous operative attempt, with just 9 having MAST as a first option. 9 patients out of 32 had a further procedure. Two patients had a further treatment directed at their OCL. Two patients had a fusion, 2 had a cheilectomy at > 4 years for impingement, one had a debridement of their anterolateral gutter, one had debridement for arthrofibrosis, one patient had a re alignment calcaneal osteotomy with debridement of their posterior tibial tendon. MAST has demonstrated positive results in lesions which prove challenging to treat, even in a “failed microfracture” cohort.

Objectives

The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing.

Articular cartilage repair remains a challenge in orthopedic surgery, as none of the current clinical therapies can regenerate the functional hyaline cartilage tissue. In this study, we proposed a one-step surgery strategy that uses autologous bone marrow mesenchymal stem cells (MSCs) embedded in type II collagen (Col-II) gels to repair the full thickness chondral defects in minipig models. Briefly, 8 mm full thickness chondral defects were created in both knees separately, one knee received Col-II + MSCs transplantation, while the untreated knee served as control. At 1, 3 and 6 months postoperatively, the animals were sacrificed, regenerated tissue was evaluated by magnetic resonance imaging, macro- and microscopic observation, and histological analysis. Results showed that regenerated tissue in Col-II + MSCs transplantation group exhibited significantly better structure compared with that in control group, in terms of cell distribution, smoothness of surface, adjacent tissue integration, Col-II content, structure of calcified layer and subchondral bone. With the regeneration of hyaline-like cartilage tissue, this one step strategy has the potential to be translated into clinical application.

It has been reported that the total steroid dose and acute rejection episodes after organ transplantation is one of the risk factors for the development of osteonecrosis of the femoral head (ONFH), and ONFH in steroid-iduced subgroup may progress more aggressively to femoral head collapse requiring total hip arthroplasty. Despite inherent medical co-morbidities of solid organ transplantation patients, most authors recently have reported successful outcomes of THAs in those patients. But there are few comparative studies on the outcome of THAs for ONFH after different organ transplantations. The purpose of this study was to evaluate and compare a single tertiary referral institution's experience of performing primary THAs in kidney transplantation (KT) and liver transplantation (LT) patients with specific focus on the total steroid dose, clinical outcomes, and relationship between ONFH and absence or presence of acute rejection (AR).

Between 1999 and 2010, 4,713 patients underwent organ transplantations (1,957 KT and 2,756 LT) and AR was occurred in 969 patients (20.6%) after transplantation. Among these patients, 131 patients (191 hips) underwent THA for ONFH, and they were retrospectively reviewed. In KT groups, there were 57 men and 36 women with a mean age of 43.7 years. In LT groups, there were 26 men and 13 women with a mean age of 50.4 years. We investigated the dose of steroid administration on both groups, the time period from transplantation to THA, Harris hips score (HHS), visual analogue scale (VAS) and complications. The mean follow up period was 8.1 years (range, 5 to 14 years).

One-hundred and thirty-one (2.8%) patients [93 KT and 38 LT] underwent THA after transplantation. The total steroid dose after transplantations was significantly higher in KT group (10,420 mg) than that in LT group (4,567 mg), but the total steroid dose in the first 2 weeks after transplantation was significantly higher in LT group (3,478 mg) than that in KT group (2,564 mg). Twenty-three (2.4%) patients (19 KT and 4 LT) who underwent THA had an episode of AR. In LT group, the total steroid dose in AR groups was significantly higher than that in non-AR groups, whereas in KT group, there was no significant difference of the total steroid dose between AR group and non-AR group. The rate of THAs for ONFH was similar in both groups (2.4% in AR group, 2.9% in non-AR group). The mean time period from transplantation to THA was 986 days for KT and 1,649 days for LT patients. Both groups showed satisfactory HHS and VAS at final follow up, revealed no differences between the groups.

The rate of THAs for ONFH was three times higher in KT patients than that in LT patients, but it was similar in both AR group and non-AR group. The total steroid dose was also higher in KT patients compared to LT patients. The clinical outcomes of THA were satisfactory with few complications in both KT and LT patients. Therefore, THAs seems to be a good option for the patients with symptomatic steroid-induced ONFH after KT and LT.

Autologous bone grafting is a standard procedure for the clinical repair of skeletal defects, and good results have been obtained. Autologous vascularized bone grafting is currently the procedure of choice because of high osteogenic potential and resistance against reabsorption. Disadvantages of this procedure include limited availability of donor sites, clinical difficulty in handling, and a failure rate exceeding 10%. Allografts are often used for massive bone loss, but since only the marginal portion is newly vascularized after the implantation non healing fractures are often reported, along with a graft reabsorption. To overcome these problems, some studies in literature tried to conjugate bone graft and vascular supply, with encouraging results. On the other side, several studies in literature reported the ability of bone marrow derived cells to promote neo-vascularization. In fact, bone marrow contains not only hematopoietic stem cells (HSCs) and MSCs as a source for regenerating tissues but also accessory cells that support angiogenesis and vasculogenesis by producing several growth factors. In this scenario a new procedure was developed, consisting in an allogenic bone graft transplantation in a critical size defect in rabbit radius, plus a deviation at its inside of the median artery and vein with a supplement of autologous bone marrow concentrate on a collagen scaffold.

Twenty-four New Zealand male white rabbits (2500–3000 g) were divided into 2 groups, each consisting of 12 animals. Surgeries were performed as follow:

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Group 1 (#12): allogenic bone graft (left radius) / allogenic bone graft + vascular pedicle + autologous bone marrow concentrate (right radius)

For each group, 3 experimental time: 8, 4 and 2 weeks (4 animals for each time).

The bone used as graft was previously collected from an uncorrelated study. An in vitro evaluation of bone marrow concentrate was performed in all cases, and at the time of sacrifice histological and histomorphometrical assessment were performed with immunohistochemical assays for VEGF, CD31 e CD146 to highlight the presence of vessels and endothelial cells. Micro-CT Analysis with quantitative bone evaluation was performed in all cases.

The bone marrow concentrate showed a marked capability to differentiate into osteogenic, chondrogenic and agipogenic lineages. No complications such as infection or intolerance to the procedure were reported. The bone grafts showed only a partial integration, mainly at the extremities in the group with vascular and bone marrow concentrate supplement, with a good and healthy residual bone. immunohistochemistry showed an interesting higher VEGF expression in the same group. Micro CT analysis showed a higher remodeling activities in the groups treated with vascular supplement, with an area of integration at the extremities increasing with the extension of the sacrifice time.

The present study suggests that the vascular and marrow cells supplement may positively influence the neoangiogenesis and the neovascularization of the homologous bone graft. A longer time of follow up and improvement of the surgical technique are required to validate the procedure.