Comorbidities are not associated with pain symptom or recurrence in patients with pilonidal disease.

BACKGROUND: Comorbidities can potentially impact the presentation or outcome of patients with pilonidal disease (PD) due to poor wound healing or increased inflammatory response. We hypothesized that certain comorbidities could lead to worse pain or higher recurrence rate. METHODS: A retrospective study was performed on all PD patients treated with standardized minimally invasive protocol at our clinic 2019-2022. Patients' demographics, comorbidities, initial/follow-up pain score, pain duration, and recurrence were recorded. Data were analyzed by t test and Chi-square test. RESULTS: Of 207 total PD patients (108 male, 99 female), 61 had comorbidities. Mean age was 18.2 years. The recurrence rate was 7%, and patients with recurrence were significantly younger. Associated comorbidities included mood/psychiatric disorders (31%), asthma/respiratory illness (30%), obesity-related illness (15%), gastrointestinal disorders (13%), diabetes (10%), thyroid disease (8%), cardiac disease (8%), musculoskeletal/connective tissue disorders (7%), immunologic disease (7%), inflammatory bowel disease (5%), and chest wall disorders (3%). The presence of comorbidities was not associated with PD recurrence. By dividing patients into adolescents (< 18 years) and adults (≥ 18 years), we found no association between comorbidity and recurrence in either group. 55% of patients had pain as an initial symptom. The initial pain score, pain duration, and pain score at follow-up were not associated with comorbidities. The comorbidities and recurrence were not associated with patient age or sex. CONCLUSIONS: Having comorbidities was not associated with pain symptoms or recurrence in PD patients. Even though patients with recurrence were younger, there was no association between comorbidity and recurrence in either adolescents or adults.

A standardized treatment protocol for pilonidal disease can influence the health mindset of adolescents.

PURPOSE: Pilonidal disease (PD) significantly impacts patients' quality of life and requires regular maintenance behaviors to achieve cure. Health mindset is a psychological construct which can influence health behaviors and outcomes, with a growth mindset being associated with better outcomes than a fixed. We propose that participation in a standardized treatment protocol can affect the health mindset for adolescents with pilonidal disease. METHODS: PD patients' demographics, recurrence, and comorbidities were prospectively collected from 2019 to 2022. We assessed patients' mindset score at initial presentation using the validated Three-Item Mindset Scale (1-6) then reassessed during follow-up. t-test was used to compare baseline and follow-up mindset scores and stratified by recurrence or comorbidities. p ≤ 0.05 was considered significant. RESULTS: A total of 207 PD patients (108 males, 99 females) with mean age 18.2 ± 3.7 years were followed for 351 ± 327 days. Mean baseline mindset score (4.76 ± 1.27) was significantly lower than mean follow-up mindset score (5.03 ± 1.18, p = 0.049). Baseline mindset score was significantly lower among patients with PD recurrence (4.00 ± 0.66) compared to those without recurrence (4.8 ± 1.29, p = 0.05). Among patients with PD recurrence, mean baseline mindset score (4.00 ± 0.66) was significantly lower than mean follow-up mindset score (5.27 ± 0.93, p = 0.0038). Patient comorbidity did not affect the baseline or follow-up mindset score. CONCLUSIONS: Participation in a standardized treatment protocol is associated with the development of a stronger growth mindset over time for patients with PD. Furthermore, a growth mindset was linked to lower recurrence rate than a fixed mindset. Further investigations into how treatment approaches can work in concert with health mindset are proposed.

Lessons Learned From the First-In-Human Compassionate Use of Connect-EA™ in Ten Patients With Esophageal Atresia.

INTRODUCTION: Delayed primary repair of esophageal atresia in patients with high-risk physiologic and anatomic comorbidities remains a daunting challenge with an increased risk for peri-operative morbidity and mortality via conventional repair. The Connect-EA device facilitates the endoscopic creation of a secure esophageal anastomosis. This follow-up study reports our long-term outcomes with the novel esophageal magnetic compression anastomosis (EMCA) Connect-EA device for EA repair, as well as lessons learned from the ten first-in-human cases. We propose an algorithm to maximize the advantages of the device for EA repair. METHODS: Under compassionate use approval, from June 2019 to December 2022, ten patients with prohibitive surgical or medical risk factors underwent attempted EMCA with this device. All patients underwent prior gastrostomy, tracheoesophageal fistula ligation (if necessary), and demonstrated pouch apposition prior to EMCA. RESULTS: Successful device deployment and EMCA formation were achieved in nine patients (90%). Mean time to anastomosis formation was 8 days (range 5-14) and the device was retrieved endoscopically in five (56%) cases. At median follow-up of 22 months (range 4-45), seven patients (78%) are tolerating oral nutrition. Balloon dilations (median 4, range 1-11) were performed either prophylactically for radiographic asymptomatic anastomotic narrowing (n = 7, 78%) or to treat clinically-significant anastomotic narrowing (n = 2, 22%) with no ongoing dilations at 3-month follow up post-repair. CONCLUSION: EMCA with the Connect-EA device is a safe and feasible minimally-invasive alterative for EA repair in high-risk surgical patients. Promising post-operative outcomes warrant further Phase I investigation. LEVEL OF EVIDENCE: IV, Case series of novel operative technique without comparison group.

Regular epilation alone is an acceptable treatment for symptom-free pilonidal patients.

INTRODUCTION: Patients with mild pilonidal disease often experience symptom resolution without excision. We hypothesized that treating symptom-free/asymptomatic pilonidal patients with regular epilation alone had similar recurrence rate as patients who were also treated surgically. METHOD: Patient data were prospectively collected 2/2019-11/2022 at our Pilonidal Clinic. All patients received regular epilation; all patients presented before 12/2020 also underwent pit excision using trephines. Starting 1/2021, only symptomatic patients underwent pit excision; symptom-free patients at presentation received only regular epilation. Recurrence rates were statistically analyzed. RESULTS: 255 patients (male:54.4%, female:45.6%), median age 17.3years (IQR:15.8-19.1) were followed for median 612.5days (IQR:367.5-847). 44.1% identified as Hispanic, 36.5% Caucasian, 17.1% Asian, 2.4% Black. Median symptom duration at presentation was 180.5days (IQR:44.5-542.5). 160 patients were initially treated with surgical excision and regular epilation, while 95 patients with regular epilation only. The failure rate between patients who received surgical excision initially and recurred (9.4%) and patients who received epilation only and recurred (12.6%) was similar, after controlling for sex, race, age, comorbidities, skin type, hair color, hair thickness (p > 0.05). Patients who recurred after only undergoing regular epilation all underwent surgical excision, median 100days (IQR:59.5-123.5) after initial presentation. CONCLUSION: Regular epilation alone is an acceptable treatment for symptom-free pilonidal patients.

Increasing Amount of Hair Reduction using Laser Correlates with Lower Probability of Recurrence in Patients with Pilonidal Disease.

BACKGROUND: Hair at the gluteal cleft plays a key role in the development and recurrence of pilonidal disease (PD). We hypothesized that more hair reduction achieved using laser could correlate with lower chance of PD recurrence. METHODS: PD patients who underwent laser epilation (LE) were categorized by Fitzpatrick skin type, hair color, and hair thickness. Photos taken at LE sessions were compared to determine hair reduction amount. LE sessions completed prior to the recurrences were recorded. Groups were compared using multivariate T-test. RESULTS: 198 PD patients had mean age 18.1 ± 3.6 years. 21, 156, and 21 patients had skin types 1/2, 3/4, and 5/6, respectively. 47 patients had light- and 151 had dark-colored hair. 29 patients had fine hair, 129 medium, and 40 thick. Median follow-up was 217 days. 95%, 70%, 40%, and 19% of patients reached 20%, 50%, 75%, and 90% hair reduction after mean LE sessions of 2.6, 4.3, 6.6, 7.8 sessions, respectively. To reach 75% hair reduction, patients require a mean of 4.8-6.8 LE sessions, depending on different skin/hair characteristics. PD recurrence rate was 6%. Probability of recurrence after 20%, 50%, 75% hair reduction was decreased by 50%, 78%, 100%, respectively. Dark hair and skin type 5/6 were associated with higher recurrence rates. CONCLUSION: Patients with dark-color and thick hair require more LE sessions to achieve certain degree of hair reduction. Patients with dark hair and skin type 5/6 were more likely to recur; more hair reduction correlated with lower chance of recurrence. LEVEL OF EVIDENCE: Level IV.

Adoption of a standardized treatment protocol for pilonidal disease leads to low recurrence.

BACKGROUND: Pilonidal disease may present as acute abscesses or chronic draining sinuses. There is no standardized treatment and recurrence rates can be as high as 30%. Within our five-hospital network we have established a standardized treatment protocol including minimally invasive surgical trephination and aggressive epilation. We hypothesize that such a treatment protocol can be established across different hospital settings and lead to low overall recurrence. METHODS: Patients with pilonidal disease were enrolled in the study on presentation to our hospital network. Those that underwent initial surgery outside our hospital system or were noncompliant with our treatment protocol were excluded. Patients were grouped based on surgeon and treating facility. Frequency of recurrence per surgeon and per hospital was calculated and compared. RESULTS: Out of 132 patients, 80 patients were included (45 female, 35 male) while 52 were excluded because of initial surgery at a non-network hospital or for protocol noncompliance. Median age was 17 (16-19) years and median length of follow-up was 352 (261-496) days. There were 6 patients who experienced at least one recurrence. There was an overall 8% recurrence rate with no significant difference noted between surgeons or hospitals (p = 0.15, p = 0.64, respectively). CONCLUSIONS: We have successfully implemented a standardized treatment protocol for pilonidal disease across different hospital settings and by different surgeons, with an overall low recurrence rate. Our findings suggest that adoption of a standardized protocol for treatment of pilonidal disease can lead to low recurrence. LEVEL OF EVIDENCE: Level IV.

Burden of pilonidal disease and improvement in quality of life after treatment in adolescents.

PURPOSE: Pilonidal Disease (PD) affects adolescents in different aspects. We hypothesized that patients with different gender, ethnicity, and age have different quality of life (QOL) measurements which could improve with minimally invasive treatment (MIT). METHODS: 131 PD patients underwent MIT (laser epilation ± trephination) from 2019 to 2021. Patients' demographics were recorded. Before and after MIT, patients received QOL questionnaire consisting of four categories: daily activities, sports participation, school/work attendance, and socializing. Data were analyzed using Student and multivariate t test. P < 0.05 was considered statistically significant. RESULTS: 101 (51 male, 50 female) patients were included. 30 patients with incomplete data were excluded. 54% of patients were < 18 years old. 47.5% were Hispanic. Median symptom duration prior to presentation was 5.4 (1.3-15) months. Prior to MIT, patients' ability to perform daily activities, participate in sports, attend school/work, and socialize was moderately or severely impacted in 66%, 57%, 45%, and 23% of respondents, respectively; after MIT, only 7%, 8%, 2%, and 4% were affected (p < 0.01). Recurrence rate was 6%. Pre-MIT, older patients and non-Hispanics reported worse impact on their QOL. Symptom duration or PD recurrence did not correlate with patient's pre- or post-MIT QOL. CONCLUSION: Patients' ethnicity and age impacted QOL in PD. All patients' QOL significantly improved with MIT. Considering the importance of socializing, playing sports, and school/work attendance in adolescents, our study highlights importance of early treatment of PD.

The novel application of an emerging device for salvage of primary repair in high-risk complex esophageal atresia.

INTRODUCTION: Preservation of native esophagus is a tenet of esophageal atresia (EA) repair. However, techniques for delayed primary anastomosis are severely limited for surgically and medically complex patients at high-risk for operative repair. We report our initial experience with the novel application of the Connect-EA, an esophageal magnetic compression anastomosis device, for salvage of primary repair in 2 high-risk complex EA patients. Compassionate use was approved by the FDA and treating institutions. OPERATIVE TECHNIQUE: Two approaches using the Connect-EA are described - a totally endoscopic approach and a novel hybrid operative approach. To our knowledge, this is the first successful use of a hybrid operative approach with an esophageal magnetic compression device. OUTCOMES: Salvage of delayed primary anastomosis was successful in both patients. The totally endoscopic approach significantly reduced operative time and avoided repeat high-risk operation. The hybrid operative approach salvaged delayed primary anastomosis and avoided cervical esophagostomy. CONCLUSION: The Connect-EA is a novel intervention to achieve delayed primary esophageal repair in complex EA patients with high-risk tissue characteristics and multi-system comorbidities that limit operative repair. We propose a clinical algorithm for use of the totally endoscopic approach and hybrid operative approach for use of the Connect-EA in high-risk complex EA patients.

Epidemiology of pediatric trauma during the COVID-19 pandemic shelter in place.

INTRODUCTION: The first COVID-19 cases occurred in the US in January of 2020, leading to the implementation of shelter in place. This study seeks to define the impact of shelter in place on the epidemiology of pediatric trauma. METHODS: We examined pediatric trauma admissions at 5 Level 1 and 1 Level 2 US pediatric trauma centers between January 1 and June 30, 2017-2020. Demographic and injury data were compared between pre- and post-shelter in place patient cohorts. RESULTS: A total of 8772 pediatric trauma activations were reviewed. There was a 13% decrease in trauma volume in 2020, with a nadir at 16 days following implementation of shelter in place. Injury severity scores were higher in the post-shelter in place cohort. The incidence of nonmotorized vehicle accidents and gunshot wounds increased in the post-shelter in place cohort. CONCLUSION: We found an overall decrease in pediatric trauma volume following shelter in place. However, injuries tended to be more severe. Our findings help inform targeted injury prevention campaigns during future pandemics.

Serial Reduction of an Extremely Large Gastroschisis using Vacuum-Assisted Closure.

We herein describe a case of serial reduction of an extremely large and complex gastroschisis using vacuum-assisted closure (VAC) therapy in a boy born at 35 5/7 weeks' gestation. A spring-loaded silicone silo was placed at birth. By day of life (DOL) 22, minimal visceral contents had been reduced, and the silo was difficult to maintain due to the size of the fascial defect and loss of abdominal domain. A bespoke VAC dressing was constructed, and biweekly dressing changes allowed gradual reduction of the gastroschisis until the viscera were consolidated. By DOL 50, the viscera were completely reduced, and VAC therapy was discontinued. Feeds were commenced on DOL 57 and increased to goal by DOL 86. The baby was discharged home on DOL 115. We conclude that VAC dressings can be used to aid gradual reduction of an extremely large gastroschisis, particularly in medical fragile infants.

A comparison of accidental and nonaccidental trauma: it is worse than you think.

BACKGROUND: Child abuse, or nonaccidental trauma (NAT), is a major cause of pediatric morbidity and mortality, and is often unrecognized. Our hypothesis was that injuries due to accidental trauma (AT) and NAT are significantly different in incidence, injury, severity, and outcome, and are often unrecognized. OBJECTIVE: Our aim was to carry out an examination of the differences between pediatric injuries due to AT and NAT regarding incidence, demographics, injury severity, and outcomes. METHODS: A 4-year retrospective review of the Trauma Registry at Children's Medical Center Dallas, a large Level I pediatric trauma center, comparing incidence, age, race, trauma activation, intensive care unit (ICU) need, Injury Severity Score (ISS), and mortality between AT and NAT patients was carried out. RESULTS: There were 5948 admissions, 92.5% were AT and 7.5% were NAT victims. The NAT patients were younger (1.8 ± 3.3 years vs. 6.8 ± 4.2 years for AT patients; p < 0.01), more often required an ICU stay (NAT 36.5% vs. 13.8% for AT patients; p < 0.0001), and had a higher ISS 14.0 ± 9.7 vs. 7.5 ± 7.2; p < 0.0001). The mortality rate in NAT was 8.9% vs. 1.4% for AT (p < 0.001). Of the 40 NAT patients who ultimately died, 17.5% were not initially diagnosed as NAT. CONCLUSIONS: NAT victims differ significantly from the AT patients, with a greater severity of injury and a 6-fold higher mortality rate. Delayed recognition of NAT occurred in almost 20% of the cases. It is generally accepted that NAT is underestimated. Its increased mortality rate and severity of injury are also not well recognized compared to the typical pediatric trauma child.

Use of an omega-3 fatty acid-based emulsion in the treatment of parenteral nutrition-induced cholestasis in patients with microvillous inclusion disease.

Microvillous inclusion disease is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. In this report, we discuss the use of a fish oil-based lipid emulsion in the treatment of 3 patients with microvillous inclusion disease who developed parenteral nutrition-associated liver disease.

Impact of surgical approach on outcome in 622 consecutive pyloromyotomies at a pediatric teaching institution.

PURPOSE: The aim of this study is to compare the outcome of 3 different approaches to pyloromyotomy in a large single institution series. METHODS: Records of consecutive patients undergoing pyloromyotomy for an 8-year period were reviewed. Patients' age, sex, weight, operating time, length of stay, number of emeses, and complications were recorded. Variables were compared between right upper quadrant (RUQ), umbilical (UMB), and laparoscopic (LAP) approaches. RESULTS: Six hundred twenty-two patients were included in the study. Operating time was significantly shorter for LAP and RUQ compared to UMB. Length of stay did not differ between the groups. There were fewer episodes of emesis in the LAP group. There was a trend toward a higher rate of complications in UMB group. CONCLUSION: Outcomes after pyloromyotomy are institution dependent and cannot be generalized. Patient safety is the first concern, followed by patient comfort and cosmesis. Laparoscopic pyloromyotomy can be as fast and efficient as open, without an increased rate of complications, with excellent cosmetic results, and less analgesic requirement. If skill and experience to replicate good outcomes of laparoscopy are not available, open pyloromyotomy is a safer technique. The UMB approach is an alternative method to achieve good cosmesis without laparoscopy in the hands of a surgeon proficient in this method.

Complete colonic duplication--a case report.

Duplications of the entire colon are very rare. An 18-month-old boy presented with symptoms of chronic constipation and was noted with a complete colonic duplication. The presentation and management are discussed.

A comparative analysis of cartilage engineered from different perinatal mesenchymal progenitor cells.

We sought to compare engineered cartilaginous constructs derived from different perinatal mesenchymal progenitor cell (MPC) sources. Ovine MPCs isolated from amniotic fluid (AF, n = 8), neonatal bone marrow (BM, n = 6), and preterm umbilical cord blood (CB, n = 12) were expanded and comparably seeded onto synthetic scaffolds. Constructs were maintained in chondrogenic media containing transforming growth factor-beta. After 12-15 weeks, specimens were compared with native fetal hyaline and elastic cartilage by gross inspection, histology, immunohistochemistry, and quantitative extracellular matrix (ECM) assays. MPCs from AF proliferated significantly faster ex vivo when compared to MPCs from the other sources. Chondrogenic differentiation was evident in all groups, as shown by toluidine blue staining and expression of aggrecan, cartilage proteoglycan link protein, and collagen type II. Quantitatively, all engineered specimens had significantly lower levels of glycosaminoglycans than native hyaline cartilage. Elastin levels in AF-based constructs (156.0 +/- 120.4 microg/mg) were comparable to that of native elastic cartilage (235.8 +/- 54.2 microg/mg), both of which were significantly higher than in BM- and CB-based specimens. We conclude that the ECM profile of cartilage engineered from perinatal MPCs is highly dependent on cell source. ECM peculiarities should be considered when designing the optimal cartilaginous bioprosthesis for use in perinatal surgical reconstruction.

Survey of pediatric surgeons on current practices of bowel preparation for elective colorectal surgery in children.

BACKGROUND: Guidelines regarding bowel preparation exist for the adult but not the pediatric population. Our aim was to evaluate the bowel preparation practices, including antibiotic usage for elective colorectal operations in children. METHODS: A survey was designed and administered to a nationwide group of pediatric surgeons to ascertain current practices of bowel preparation. RESULTS: Four hundred ninety-three surveys were administered, and 136 physicians responded (28%). Mechanical bowel preparation was used by 96% of the respondents. Preoperative intravenous antibiotics were used by 99% of respondents. The number of years in practice did not significantly affect the use of oral antibiotics (P = .62) or the duration of intravenous antibiotics (P = .78). CONCLUSIONS: There is a wide variation in bowel preparation practices in children. A prospective, randomized trial would be helpful to identify the role of oral antibiotics and optimal duration of intravenous antibiotics in this population.

Postnatal myocardial augmentation with skeletal myoblast-based fetal tissue engineering.

BACKGROUND: Cardiac anomalies constitute the most common birth defects, many of which involve variable myocardial deficiencies. Therapeutic options for structural myocardial repair remain limited in the neonatal population. This study was aimed at determining whether engineered fetal muscle constructs undergo milieu-dependent transdifferentiation after cardiac implantation, thus becoming a potential means to increase/support myocardial mass after birth. METHODS: Myoblasts were isolated from skeletal muscle specimens harvested from fetal lambs, labeled by transduction with a retrovirus-expressing green fluorescent protein, expanded in vitro, and then seeded onto collagen hydrogels. After birth, animals underwent autologous implantation of the engineered constructs (n = 8) onto the myocardium as an onlay patch. Between 4 and 30 weeks postoperatively, implants were harvested for multiple analyses. RESULTS: Fetal and postnatal survival rates were 89% and 100%, respectively. Labeled cells were identified within the implants at all time points by immunohistochemical staining for green fluorescent protein. At 24 and 30 weeks postimplantation, donor cells double-stained for green fluorescent protein and Troponin I, while losing skeletal (type II) myosin expression. CONCLUSIONS: Fetal skeletal myoblasts engraft in native myocardium up to 30 weeks after postnatal, autologous implantation as components of engineered onlay patches. These cells also display evidence of time-dependent transdifferentiation toward a cardiomyocyte-like lineage. Further analysis of fetal skeletal myoblast-based constructs for the repair of congenital myocardial defects is warranted.

Fetal hepatic haematopoiesis is modulated by arterial blood flow to the liver.

We describe an as yet unrecognised relationship between fetal hepatic haematopoiesis and arterial blood flow to the liver. To increase hepatic arterial flow, the common bile duct (CBD) was ligated in fetal lambs. Reduction of hepatic arterial flow was accomplished in age-matched animals by hepatic artery (HA) ligation. Multiple analyses performed before term showed a significant increase in haematopoietic cell density in CBD animals when compared with sham controls and HA animals. In contrast, HA animals demonstrated a decrease in liver haematopoietic activity. Fetal hepatic haematopoiesis is dependent upon arterial blood flow to the liver.

Diaphragmatic repair through fetal tissue engineering: a comparison between mesenchymal amniocyte- and myoblast-based constructs.

PURPOSE: We have previously shown that fetal tissue engineering is a preferred alternative to diaphragmatic repair in a large animal model. This study was aimed at comparing diaphragmatic constructs seeded with mesenchymal amniocytes and fetal myoblasts in this model. METHODS: Neonatal lambs (n = 14) underwent repair of an experimental diaphragmatic defect with identical scaffolds, either seeded with labeled autologous cells (mesenchymal amniocytes in group 1 and fetal myoblasts in group 2) or as an acellular graft (group 3). At 1 to 12 months postoperatively, implants were harvested for multiple analyses. RESULTS: Repair failure (reherniation or eventration) was significantly higher in group 3 than in groups 1 and 2, with no difference between groups 1 and 2. Seeded fetal myoblasts quickly lost their myogenic phenotype in vivo. All grafts contained cells with a fibroblastic-myofibroblastic profile. Elastin concentrations and both modular and ultimate tensile strengths were significantly higher in group 1 than in groups 2 and 3. There were no differences in glycosaminoglycans and type I collagen levels among the groups. CONCLUSIONS: Diaphragmatic repair with a mesenchymal amniocyte-based engineered tendon leads to improved structural outcomes when compared with equivalent fetal myoblast-based and acellular grafts. The amniotic fluid is a preferred cell source for tissue-engineered diaphragmatic reconstruction.

Hydrogel optimization for cultured elastic chondrocytes seeded onto a polyglycolic acid scaffold.

The purpose of this study was to compare the effect of different hydrogels on the production of tissue-engineered cartilage based on polyglycolic acid (PGA). Chondrocytes were isolated from adult sheep auricles. Alginate, Type I collagen, methylcellulose, and pluronic F127 hydrogels were evaluated, as were controls prepared without hydrogels. Proliferated chondrocytes were mixed with each hydrogel at 20 x 10(6) cells/mL and seeded onto PGA (1 x 1 x 0.2 cm, n = 60). The constructs were cultured with serum-free medium containing 5 ng/mL TGF-beta(2) and 5 ng/mL des(1-3)IGF-I in rotational bioreactors for up to 6 weeks. The cellular morphology, histology, and biochemistry were analyzed. Type I collagen, methylcellulose, and pluronic F127 displayed improved cartilage matrix deposition in terms of histology and biochemistry compared to alginate. It was not concluded that the combined seeding of chondrocytes and hydrogels on a PGA scaffold had significantly better effects than cell seeding without hydrogels. However, the histology and other useful findings in this ECM analyses suggested that Type I collagen and MC hydrogels were the best candidates for cartilage regeneration, because of their stimulation for chondrocyte proliferation in a three-dimensional culture as well as cartilage regeneration.