Single-Stage Arthroscopic Cartilage Repair With Chondrectomy and Implantation of a Templated Membrane Collagen Scaffold With Bone Marrow Aspirate Concentrate Augmentation (AMIC Plus).

Single-staged cartilage repair techniques have shown great clinical efficacy in the treatment of articular cartilage defects of the knee, particularly when using bilayered acellular scaffolds augmented with bone marrow aspirate concentrate. We describe an all-arthroscopic approach to the single-staged cartilage repair procedure using a porcine-derived collagen I/III bilayered scaffold that is templated arthroscopically and augmented with bone marrow aspirate concentrate, in the treatment of critically sized articular defects of the knee.

Small extracellular vesicles from mesenchymal stromal cells: the next therapeutic paradigm for musculoskeletal disorders.

Musculoskeletal disorders are one of the biggest contributors to morbidity and place an enormous burden on the health care system in an aging population. Owing to their immunomodulatory and regenerative properties, mesenchymal stromal/stem cells (MSCs) have demonstrated therapeutic efficacy for treatment of a wide variety of conditions, including musculoskeletal disorders. Although MSCs were originally thought to differentiate and replace injured/diseased tissues, it is now accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly extracellular vesicles (EVs). Endowed with a diverse cargo of bioactive lipids, proteins, nucleic acids and metabolites, MSC-EVs have been shown to elicit diverse cellular responses and interact with many cell types needed in tissue repair. The present review aims to summarize the latest advances in the use of native MSC-EVs for musculoskeletal regeneration, examine the cargo molecules and mechanisms underlying their therapeutic effects, and discuss the progress and challenges in their translation to the clinic.

Does the Choice of Acellular Scaffold and Augmentation With Bone Marrow Aspirate Concentrate Affect Short-term Outcomes in Cartilage Repair? A Systematic Review and Meta-analysis.

BACKGROUND: Matrix-induced chondrogenesis (MIC) is a promising treatment option for critical-size cartilage lesions of the knee; however, there exists substantial heterogeneity in the choice of acellular scaffold matrix for MIC cartilage repairs. HYPOTHESIS: The choice of acellular matrix will not affect patient outcomes after MIC cartilage repair procedures, and the addition of concentrated bone marrow aspirate (cBMA) will improve short-term patient outcomes regardless of matrix choice. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: Studies were stratified by matrix type: multilayered, single layered, and gel based. Continuous outcomes were analyzed with pairwise meta-analysis using the inverse variance model with random effects applied. Binary outcomes were analyzed as pooled proportions in a single-arm fashion; after which, reconstruction of relative risks (RRs) with confidence intervals was performed using the Katz logarithmic method. RESULTS: A total of 876 patients were included: 469 received multilayered bioscaffolds; 238, gel-based scaffolds; and 169, single-layered scaffolds. The mean age of patients was 36.2 years (95% CI, 33.9 to 38.4), while the mean lesion size was 3.91 cm2 (95% CI, 3.40 to 4.42). The weighted mean follow-up was 23.8 months (95% CI, 20.1 to 27.6). Multilayered bioscaffolds were most effective at improving visual analog scale scores (P = .03; weighted mean difference [WMD], -4.44 [95% CI, -4.83 to -4.06]; P < .001). There were significantly lower risks of incomplete defect filling for gel-based scaffolds when compared with multilayered scaffolds (RR, 0.78 [95% CI, 0.69 to 0.88]; P < .001) and single-layered scaffolds (RR, 0.58 [95% CI, 0.41 to 0.81]; P = .001). Augmentation with cBMA further improved clinical scores across all scaffolds, with significant improvements in Tegner score (P = .02), while decreasing incomplete defect filling rates as well. There was significantly greater improvement in visual analog scale scores (P = .01) for single-layered scaffolds with cBMA augmentation (WMD, -4.88 [95% CI, -5.38 to -4.37]; P < .001) as compared with single-layered scaffolds without cBMA augmentation (WMD, -4.08 [95% CI, -4.46 to -3.71]; P < .001). All significant improvements were below their respective minimum clinically important differences. CONCLUSION: While cartilage repair with acellular scaffolds provides significant improvements in pain and function for patients, there is insufficient clinical evidence to suggest which scaffold material is the most superior in influencing such improvements. The enhancement of cartilage repair procedures with cBMA may provide further functional improvements and improve defect filling; however, more long-term evidence is required to evaluate the effects.

Biomaterials for meniscus and cartilage in knee surgery: state of the art.

Meniscus and cartilage injuries of the knee joint lead to cartilage degeneration and osteoarthritis (OA). The research on biomaterials and artificial implants as substitutes in reconstruction and regeneration has become a main international focus in order to solve clinical problems such as irreparable meniscus injury, postmeniscectomy syndrome, osteochondral lesions and generalised chronic OA. In this review, we provide a summary of biomaterials currently used in clinical practice as well as state-of-the-art tissue engineering strategies and technologies that are developed for articular cartilage and meniscus repair and regeneration. The literature was reviewed over the last 5 years on clinically used meniscus and cartilage repair biomaterials, such as Collagen Meniscal Implant, Actifit, NUsurface, TruFit, Agili-C and MaioRegen. There are clinical advantages for these biomaterials and the application of these treatment options should be considered individually. Standardised evaluation protocols are needed for biological and mechanical assessment and comparison between different scaffolds, and long-term randomised independent clinical trials with large study numbers are needed to provide more insight into the use of these biomaterials. Surgeons should become familiar and stay up to date with evolving repair options to improve their armamentarium for meniscal and cartilage defects.

Mesenchymal Stem Cell Exosomes Promote Growth Plate Repair and Reduce Limb-Length Discrepancy in Young Rats.

BACKGROUND: The objective of this study was to examine the therapeutic effects of human mesenchymal stromal/stem cell (MSC) exosomes in a rat model of growth plate injury. METHODS: A growth plate defect was surgically created on the distal part of the right femur of 40 female Sprague-Dawley rats. A single intra-articular injection of 100 µg of MSC exosomes in 100 µL of phosphate-buffered saline solution (PBS), or an equivalent volume of PBS alone, was administered to the right knee immediately after surgery. At 4 and 8 weeks post-treatment, limb length was measured with micro-CT, and tissue repair was assessed with histological, immunohistochemical, and histomorphometric analyses. RESULTS: A single injection of MSC exosomes significantly increased limb length from 3.29 ± 0.07 cm at 4 weeks to 3.37 ± 0.11 cm at 8 weeks (p = 0.047). However, no improvement in limb length was observed in the PBS control group. The limb-length discrepancy between the involved limb and the contralateral limb in the exosome-treated group was significantly less than the discrepancy in the PBS-treated group at both 4 weeks (2.52% ± 1.30% versus 4.11% ± 0.93%; p = 0.006) and 8 weeks (5.27% ± 2.11% versus 8.06% ± 2.56%; p = 0.016). Consistent with the reduced limb-length discrepancy, the exosome-treated defects displayed significantly more chondrocytes (p < 0.05) and a higher area percentage with deposition of sulphated glycosaminoglycan (p < 0.05) and collagen II (p < 0.05) than PBS-treated defects at 8 weeks. However, bone bridge formation was not inhibited in either group. CONCLUSIONS: A single intra-articular injection of MSC exosomes significantly enhanced physeal repair and reduced limb-length discrepancy but did not inhibit bone-bridge formation. CLINICAL RELEVANCE: This proof-of-concept study demonstrates for the first time the potential use of MSC exosomes as a minimally invasive cell-free therapeutic to promote physeal repair and reduce limb-length discrepancy following growth plate injuries.

Mesenchymal Stem Cell Exosomes Promote Functional Osteochondral Repair in a Clinically Relevant Porcine Model.

BACKGROUND: Previous studies have reported the efficacy of human mesenchymal stem cell (MSC) exosomes for the repair of osteochondral defects in rats and rabbits. However, the safety and efficacy of MSC exosomes remain to be validated in a clinically relevant large animal model. PURPOSE: To validate the safety and efficacy of human MSC exosomes for osteochondral repair in a clinically relevant micropig model. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral osteochondral defects (6-mm diameter and 1-mm depth) were surgically created in the medial femoral condyles in knees of 12 micropigs. The pigs then received 2-mL intra-articular injections of MSC exosomes and hyaluronic acid (HA) (Exosome+HA) or HA alone after surgery and thereafter at 8 and 15 days. Osteochondral repair was assessed by magnetic resonance imaging (MRI) at 15 days and at 2 and 4 months after surgery as well as by macroscopic, histological, biomechanical, and micro-computed tomography (micro-CT) analyses at 4 months after surgery. RESULTS: Exosome+HA-treated defects demonstrated significantly better MRI scores than HA-treated defects at 15 days and at 2 and 4 months. Additionally, Exosome+HA-treated defects demonstrated functional cartilage and subchondral bone repair, with significantly better macroscopic and histological scores and biomechanical properties (Young modulus and stiffness) than HA-treated defects at 4 months. Micro-CT further showed significantly higher bone volume and trabecular thickness in the subchondral bone of Exosome+HA-treated defects than that of HA-treated defects. Importantly, no adverse response or major systemic alteration was observed in any of the animals. CONCLUSION: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 weekly intra-articular injections can promote functional cartilage and subchondral bone repair, with significantly improved morphological, histological, and biomechanical outcomes in a clinically relevant porcine model. CLINICAL RELEVANCE: Our findings provide a robust scientific rationale to support a phase 1/2 clinical trial to test MSC exosomes in patients with osteochondral lesions.

Securing Transplanted Meniscal Allografts Using Bone Plugs Results in Lower Risks of Graft Failure and Reoperations: A Meta-analysis.

BACKGROUND: Meniscal allograft transplant (MAT) is an important treatment option for young patients with deficient menisci; however, there is a lack of consensus on the optimal method of allograft fixation. HYPOTHESIS: The various methods of MAT fixation have measurable and significant differences in outcomes. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A single-arm meta-analysis of studies reporting graft failure, reoperations, and other clinical outcomes after MAT was performed. Studies were stratified by suture-only, bone plug, and bone bridge fixation methods. Proportionate rates of failure and reoperation for each fixation technique were pooled with a mixed-effects model, after which reconstruction of relative risks with confidence intervals was performed using the Katz logarithmic method. RESULTS: A total of 2604 patients underwent MAT. Weighted mean follow-up was 4.3 years (95% CI, 3.2-5.6 years). During this follow-up period, graft failure rates were 6.2% (95% CI, 3.2%-11.6%) for bone plug fixation, 6.9% (95% CI, 4.5%-10.3%) for suture-only fixation, and 9.3% (95% CI, 6.2%-13.9%) for bone bridge fixation. Transplanted menisci secured using bone plugs displayed a lower risk of failure compared with menisci secured via bone bridges (RR = 0.97; 95% CI, 0.94-0.99; P = .02). Risks of failure were not significantly different when comparing suture fixation to bone bridge (RR = 1.02; 95% CI, 0.99-1.06; P = .12) and bone plugs (RR = 0.99; 95% CI, 0.96-1.02; P = .64). Allografts secured using bone plugs were at a lower risk of requiring reoperations compared with those secured using sutures (RR = 0.91; 95% CI, 0.87-0.95; P < .001), whereas allografts secured using bone bridges had a higher risk of reoperation when compared with those secured using either sutures (RR = 1.28; 95% CI, 1.19-1.38; P < .001) or bone plugs (RR = 1.41; 95% CI, 1.32-1.51; P < .001). Improvements in Lysholm and International Knee Documentation Committee scores were comparable among the different groups. CONCLUSION: This meta-analysis demonstrates that bone plug fixation of transplanted meniscal allografts carries a lower risk of failure than the bone bridge method and has a lower risk of requiring subsequent operations than both suture-only and bone bridge methods of fixation. This suggests that the technique used in the fixation of a transplanted meniscal allograft is an important factor in the clinical outcomes of patients receiving MATs.

All-Cause Failure Rates Increase With Time Following Meniscal Repair Despite Favorable Outcomes: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this review is to perform a meta-analysis of studies reporting meniscus repair outcomes. Pooled analyses of such studies will provide an accurate estimate of the outcomes that can be expected following meniscal repair at various postoperative time points. METHODS: A meta-analysis of meniscal repair failure (defined as persistent symptoms, lack of healing on magnetic resonance imaging or revision surgery) and other clinical outcomes was performed following meniscal repair. Patients included had traumatic, nondegenerative meniscal tears, were skeletally mature, and had specific time-points after surgery. Repairs included were performed either in isolation, or with concomitant ACL reconstruction. Because of the inherent heterogeneity of single-arm meta-analyses, pooled analyses were performed using a random-effects model. RESULTS: Rates of all-cause meniscal repair failure was pooled to be 12% at 0-1 years (95% CI: .09-.16), 15% at 2-3 years (95% CI: .11-.20), and 19% at 4-6 years (95% CI: .13-.24). Sensitivity analysis for studies performing meniscal repair entirely on patients with concomitant ACL reconstruction (ACLR) showed comparable rates of failure at similar time intervals. Development of osteoarthritis, in patients with knees previously free from articular pathologies, was 4% at 2-3 years (95% CI: .02-.07), and 10% at 4-6 years (95% CI: .03-.25). CONCLUSION: Meniscus repair for traumatic injuries have an all-cause failure rate that increases from 12% to 19% through a time period ranging from 1-6 years following surgery. The failure rates were comparable for patients with meniscal repairs performed with concomitant ACLRs. LEVEL OF EVIDENCE: IV; Systematic Review of Level II-IV Studies.

Bisphosphonate therapy after liver transplant improves bone mineral density and reduces fracture rates: an updated systematic review and meta-analysis.

To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post-orthotopic liver transplant (OLT) patients. Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post-OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta-analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single-arm meta-analysis. Post-OLT fracture incidence was reported in nine studies (n = 591). Total fracture incidence was 6.6% (CI: 3.4-12.4%) in bisphosphonate group and 19.1% (CI: 14.3-25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n = 591; OR = 0.037; CI: 0.18-0.77; P = 0.008). Overall fractures were significantly lower in the oral group (n = 263; OR = 0.26; CI: 0.08-0.85; P = 0.02) but not in the IV group (n = 328; OR = 0.45; CI: 0.16-1.26; P = 0.129). Both oral and IV bisphosphonates are effective in reducing fracture incidence post-OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post-OLT.

A systematic review and meta-analysis on the incidence of osteoporosis and fractures after liver transplant.

Following liver transplant (LT), osteoporosis is a severe complication that causes morbidity. However, the incidence and risk factors of osteoporosis and fractures have not been well described. Single-arm meta-analysis of studies reporting osteopenia, osteoporosis, and fractures post-LT was performed with meta-regression for study period. Dichotomous variables, continuous variables and time-to-event variables were pooled in odds ratio, weighted mean difference and hazard ratio, respectively. For risk factors with limited data, a systematic review of literature was conducted. There was a significant increase in both osteoporosis and fractures compared to non-LT patients. Osteopenia, osteoporosis and incident fractures were newly diagnosed in 34.53% (CI: 0.17-0.56, n = 301), 11.68% (CI: 0.05-0.24, n = 1251) and 20.40% (CI: 0.13-0.30, n = 4322) of LT patients, respectively. Female gender (P = 0.017) increased risks of osteoporosis but not older age and BMI. Older age, lower pre-LT bone mineral density (BMD), presence of bone disease pre-LT were significant risk factors for fractures but not female gender, post-menopausal state, BMI, smoking and alcohol. There is a high incidence of skeletal complications post-LT. Older age, lower pre-LT BMD and presence of bone disease pre-LT are significant risk factors that are associated with incident fractures physicians should be cognisant of in liver transplant recipients.

Intra-articular Injections of Mesenchymal Stem Cells Without Adjuvant Therapies for Knee Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: While many reviews have been performed to attempt to provide conclusive evidence regarding the outcomes of mesenchymal stem cells (MSCs) in osteoarthritis treatment, the evidence for MSC treatment in osteoarthritis remains contentious, as these reviews have been limited by the heterogeneous evidence available. PURPOSE: To pool the results of treatment using intra-articular injections of MSCs without any adjuvant therapies for osteoarthritis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All clinical trials of level 1 or 2 evidence that reported clinical outcomes of patients with osteoarthritis of the knees treated using intra-articular injections of MSCs without any adjuvant therapies were included. RESULTS: A total of 19 studies with 440 knees were included. All studies reported an improvement in the outcomes after intervention. The standardized mean differences (SMDs) for the visual analog scale (VAS) for pain at rest and upon exertion were -1.48 (95% CI, -1.85 to -1.11) and -2.25 (95% CI, -2.64 to -1.85), respectively. The SMDs for the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and total Knee injury and Osteoarthritis Outcome Score were -1.19 (95% CI, -1.53 to -0.84) and 0.88 (95% CI, 0.66-1.10), respectively. Only the source of MSCs and whether the MSCs were cultured or uncultured were clinically important and statistically significant moderators of the treatment outcome. The use of bone marrow MSCs reduced the VAS for pain by 1.50 (95% CI, 0.04-2.96; P = .04) and reduced the total WOMAC by 23.2 (95% CI, 10.0-36.4; P < .01) as compared with adipose MSCs. The use of cultured MSCs reduced the VAS for pain by 2.19 (95% CI, 0.57-3.81; P < .01) and reduced the total WOMAC by 14.4 (95% CI, 1.21-27.5; P = .03) as compared with uncultured MSCs. CONCLUSION: Intra-articular injections of MSCs without any adjuvant therapies improves pain and function for osteoarthritis. Significantly better outcomes were obtained with the use of bone marrow MSCs as compared with adipose MSCs and with the use of cultured MSCs as opposed to uncultured MSCs.

Epidemiology of patients with anterior cruciate ligament injuries undergoing reconstruction surgery in a multi-ethnic Asian population.

We conducted an epidemiological study to identify the demographics and pre-operative characteristics of patients undergoing primary anterior cruciate ligament (ACL) reconstruction in a multi-ethnic Asian population. A retrospective study was performed on 696 patients who registered in our ACL reconstruction registry from January 2013 to August 2016. Important inter-ethnic differences were found. Indian patients were significantly older compared to Malay and Chinese patients. Malay and Indian patients were more likely to be male, overweight, and obese compared to Chinese patients. Soccer was the predominant sport involved, although ethnic predominance in specific sports exists. Novel findings from this study include increased prevalence of concomitant chondral injuries in the Chinese population compared to Malays and Indians, and significantly higher rates of concomitant intra-articular injuries in soccer and basketball compared to netball. Identification of these high-risk subgroups would serve useful in guiding the formulation of prevention strategies within our multi-ethnic community.

Mesenchymal Stem Cell Exosomes for Cartilage Regeneration: A Systematic Review of Preclinical In Vivo Studies.

Clinical and animal studies have demonstrated efficacy of mesenchymal stem/stromal cells (MSCs) in cartilage repair. Although MSCs were originally predicated to mediate tissue repair through cellular differentiation and cell replacement, it is now recognized that MSCs exert most of their paracrine effects on tissue repair through the release of extracellular vesicles (EVs). In particular, 50-200 nm small EVs that also include exosomes carry a rich cargo of lipids, nucleic acids, and proteins, and have been reported to be therapeutically efficacious in various disease indications, including osteochondral injuries and osteoarthritis (OA). This systematic review aimed to assess the preclinical studies that used MSC exosomes for cartilage repair. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, PubMed and Cochrane Library databases were searched for relevant controlled preclinical animal studies. A total of 13 studies were identified, with the total sample size being 434. This included 378 (87.1%) mice or rats and 56 (12.9%) rabbits. According to Systematic Review Centre for Laboratory Animal Experimentation risk of bias assessment, all the studies presented with unclear-to-low risk in bias. In general, MSC exosomes were found to be efficacious in promoting repair and regeneration of osteochondral defects and alleviating OA degeneration. In most studies, exosome-treated animals displayed increased cellular proliferation, enhanced matrix deposition, and improved histological scores. Having assessed the relevant preclinical animal studies reported to date, this systematic review shows the therapeutic benefit of MSC exosome therapy in cartilage repair. Standardization of animal models and outcome measurements would be needed to facilitate more robust analysis and improve the validity of the results in future studies.

Radiographic Outcomes Following the Suture Fixation of Mid-pole Patellar Fractures.

Background Mid-pole patellar fractures are typically fixed with metal implants in the conventional "11-8" tension band construct. However, this technique is fraught with numerous implant-related complications. The aim of this study is to evaluate the union rate following "all-suture" fixation of mid-pole patellar fractures. Methods We retrospectively evaluated a consecutive case series of patients with displaced mid-pole patella fractures treated with "all-suture" fixation in our institution. Fifteen cases were available for this study. The average age was 61.5 years. Clinical and radiological outcomes were evaluated. Union time, complications, and revision rate were recorded. The minimum follow-up was one year. Results There were eight males and seven females, with a mean age of 61.5 ± 13.3 years. Fourteen out of 15 cases (93.3%) achieved radiographic union at 12 weeks postoperatively. The average time to radiographic union was 8.0 ± 2.7 weeks. Five cases (33.3%) had an increase in the fracture gap (>2 mm) at around four to six weeks postoperatively. Four of these cases had an eventual union, whereas one patient had fibrous non-union. There was one case of superficial surgical site infection and one case of infected hematoma. None of the patients required revision surgery. Conclusion "All-suture" fixation of mid-pole transverse patellar fractures is a safe and viable alternative to the conventional "11-8" tension band constructs with metal implants, with good union time, rates, and added benefits of not requiring additional surgery for implant removal.

Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model.

PURPOSE: To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model. METHODS: Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated. RESULTS: Compared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks. CONCLUSIONS: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone. CLINICAL RELEVANCE: Human MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.

Negative Pressure Wound Therapy With Instillation and Dwell Time Used to Treat a Deep Foot Abscess With a Small Plantar Surface Incision.

INTRODUCTION: Deep soft tissue wounds have a significant volume of dead space that often delays healing. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) used as an irrigation channel to manage deep cavity wounds with a tunneled opening has yet to be described to the authors' knowledge. CASE REPORT: The patient presented with pain and swelling of the left foot along with fever, elevated inflammatory markers, and signs of infection. Antibiotics were initially provided. Surgical debridement with a minimally invasive incision revealed a deep midfoot plantar abscess and resulted in a 2.2 cm wound with a cavity extending 5 cm from the second to fourth metatarsophalangeal joints, initially managed with topical dressings. At postoperative day 5, NPWTi-d (-125 mm Hg) with instillation of betadine-polyhexanide solution and dwell time of 10 minutes was initiated and provided twice weekly for 2 weeks. Clinicians created a foam dressing irrigation channel that enabled cleansing of the entire wound and reduced the volume of dead space within the cavity. A hydrocolloid dressing was used to protect wound edges. The type of NPWT system was changed as healing progressed. No repeat surgical debridement was required, and inflammatory markers down trended over the course of the 3-week hospital admission. The deep cavity wound demonstrated good progress with healing, and eventually healed completely by 2 months from initial surgical debridement. CONCLUSIONS: In a deep cavity wound with a small tunneled opening, NPWTi-d used as an irrigation channel is effective in reducing dead space and removing debris, in addition to avoiding the need for multiple surgical debridements and minimizing dressing change frequency.

Negative Pressure Wound Therapy With Instillation and Dwell Time Modifications for Lower Limb Wounds With the Waterfall Technique: A Case Series.

BACKGROUND: Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is an integrated system that combines conventional NPWT with an irrigation feature. Wound size and location of diabetic foot wounds may make NPWTi-d utilization difficult, commonly resulting in leakages and blockages. OBJECTIVE: This study evaluates the effectiveness of a novel waterfall technique, a modification of the usual bridging used during NPWTi-d application, to facilitate the channeling of instillation fluid into diabetic foot wounds with small entry points. MATERIALS AND METHODS: A literature review of NPWTi-d use in the treatment of infected diabetic foot wounds and a case series of 9 patients with infected diabetic foot wounds who were admitted to a tertiary health care institution from September 2019 to May 2020 were carried out. RESULTS: Six patients were male and 3 were female, with a median age of 56 years (range, 45-67 years). All patients underwent a surgical procedure of the infected foot wounds (7 minor ray amputations, 2 wound debridements). All resultant wounds were ray amputation wounds over the metatarsals, except for one wound over the plantar midfoot. Wound sizes ranged from 2 cm x 4 cm x 4 cm to 11 cm x 4 cm x 8 cm. Median duration from surgery to initialization of NPWTi-d was 2 days (range, 1-22 days). Only 1 case reported a leak in NPWTi-d, which was resolved with minor adjustments and without changing the dressing in its entirety; no incidents of blockage were encountered. None of the patients required repeat surgical debridement during index hospitalization, and full epithelialization was achieved in 88.9% of patients. CONCLUSIONS: The waterfall technique ensures placement of the NPWTi-d tubing pad in a dependent position to improve flow of instillation fluid with minimal risk of leakage or blockage.