Extracellular Matrix Patch Research Articles

Composite Biosynthetic Graft for Repair of Long-Segment Tracheal Stenosis: A Pilot In Vivo and In Vitro Feasibility Study.

Pediatric patients who undergo surgery for long-segment congenital tracheal stenosis (LSCTS) have suboptimal outcomes and postsurgical complications. To address this, we propose a biosynthetic graft comprising (1) a porcine small intestinal submucosa extracellular matrix (SIS-ECM) patch for tracheal repair, and (2) a resorbable polymeric exostent for biomechanical support. The SIS-ECM patch was evaluated in vivo in an ovine trachea model over an 8 month period. Concurrently, the biosynthetic graft was evaluated in a benchtop lamb trachea model for biomechanical stability. In vivo results show that SIS-ECM performs better than bovine pericardium (control) by preventing granulation tissue/restenosis, restoring tracheal architecture, blood vessels, matrix components, pseudostratified columnar and stratified epithelium, ciliary structures, mucin production, and goblet cells. In vitro tests show that the biosynthetic graft can provide the desired axial and flexural stability, and biomechanical function approaching that of native trachea. These results encourage future studies to evaluate safety and efficacy, including biomechanics and collapse risk, biodegradation, and in vivo response enabling a stable long-term tracheal repair option for pediatric patients with LSCTS and other tracheal defects.

Second-generation extracellular matrix patch for epicardial infarct repair

Current myocardial infarction treatments focus on improving hemodynamics rather than addressing the problem of lost myocardium impairing left ventricular function. Epicardial infarct repair with a bioactive patch placed on the ischemic area is an emerging approach to promote endogenous myocardial repair. We report the use of a second-generation CorMatrix-extracellular matrix (ECM) patch as an adjunct to surgical revascularization in treating a young patient with diffuse, multivessel coronary artery disease unamenable to PCI and a large anterior myocardial infarction. The progressive myocardial scar shrinkage and increase in left ventricular ejection fraction from 10 to 51% are generally not observed with surgical revascularization therapy alone, suggesting this new patch has adjunctive potential to current revascularization therapy.

Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts; however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.

Erectile Dysfunction Treatment Using Stem Cell Delivery Patch in a Cavernous Nerve Injury Rat Model.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering for post-prostatectomy ED has been attempted in which controlled interactions between cells, growth factors, and the extracellular matrix (ECM) are important for the structural integrity if nerve regeneration. In this study, we evaluated the effects of a biomechanical ECM patch on the morphology and behavior of human bone marrow-derived mesenchymal stem cells (hBMSCs) in a bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratios, higher ratios of smooth muscle to collagen, increased nNOS content, higher levels of eNOS protein expression, and higher cGMP levels compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Tissue-Adhesive Decellularized Extracellular Matrix Patches Reinforced by a Supramolecular Gelator to Repair Abdominal Wall Defects.

Implantation of surgical meshes composed of synthetic and biological materials has been applied for abdominal wall defect repair. Despite many efforts, there are no reliable meshes that fully satisfy clinical requirements because of their lack of biodegradability, mechanical strength, and tissue-adhesive properties. Here, we report biodegradable, decellularized extracellular matrix (dECM)-based biological patches to treat abdominal wall defects. By incorporating a water-insoluble supramolecular gelator that forms physical cross-linking networks through intermolecular hydrogen bonding, dECM patches were reinforced to improve mechanical strength. Reinforced dECM patches possessed higher tissue adhesion strength and underwater stability compared with the original dECM because of enhanced interfacial adhesion strength. In vivo experiments using an abdominal wall defect rat model showed that reinforced dECM patches induced collagen deposition and the formation of blood vessels during material degradation, and the accumulation of CD68-positive macrophages was suppressed compared to nonbiodegradable synthetic meshes. Tissue-adhesive and biodegradable dECM patches with improved mechanical strength by a supramolecular gelator have enormous potential for use in the repair of abdominal wall defects.

Epicardial transplantation of autologous atrial appendage micrografts: evaluation of safety and feasibility in pigs after coronary artery occlusion

Objectives. Several approaches devised for clinical utilization of cell-based therapies for heart failure often suffer from complex and lengthy preparation stages. Epicardial delivery of autologous atrial appendage micrografts (AAMs) with a clinically used extracellular matrix (ECM) patch provides a straightforward therapy alternative. We evaluated the operative feasibility and the effect of micrografts on the patch-induced epicardial foreign body inflammatory response in a porcine model of myocardial infarction. Design. Right atrial appendages were harvested and mechanically processed into AAMs. The left anterior descending coronary artery was ligated to generate acute infarction. Patches of ECM matrix with or without AAMs were transplanted epicardially onto the infarcted area. Four pigs received the ECM and four received the AAMs patch. Cardiac function was studied by echocardiography both preoperatively and at 3-week follow-up. The primary outcome measures were safety and feasibility of the therapy administration, and the secondary outcome was the inflammatory response to ECM. Results. Neither AAMs nor ECM patch-related complications were detected during the follow-up time. AAMs patch preparation was feasible according to time and safety. Inflammation was greatly reduced in AAMs when compared with ECM patches as measured by the amount of infiltrated inflammatory cells and area of inflammation. Immunohistochemistry demonstrated an increased CD3+ cell density in the AAMs patch infiltrate. Conclusions. Epicardial AAMs transplantation demonstrated safety and clinical feasibility. The use of micrografts significantly inhibited ECM-induced foreign body inflammatory reactivity. Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can suppress acute inflammatory reactivity.

Is Porcine Small Intestinal Submucosal Extracellular Matrix (ECM) a Suitable Material for Right Ventricular Outflow Tract Reconstruction in Association With Pulmonary Valve Replacement?

Pulmonary valve replacement (PVR) with right ventricular outflow tract (RVOT) reconstruction is a common congenital cardiac operation. Porcine submucosal intestinal-derived extracellular matrix (ECM) patches have been used for RVOT reconstruction. We present 2 adult patients with Tetralogy of Fallot who underwent PVR with RVOT reconstruction utilizing ECM. Both cases required reoperation due to patch dehiscence causing a large paravalvular leak. One patient also had a pseudoaneurysm associated with ECM dehiscence. There may be a propensity for ECM dehiscence in this application and, based on these cases, we recommend avoidance of ECM in RVOT reconstruction with PVR. PVR patients repaired with ECM should be monitored for this complication.

More Than 400 Uses of an Intestinal Submucosal Extracellular Matrix Patch in a Congenital Heart Program

BackgroundRepair of complex congenital heart disease frequently requires use of a patch as an anatomic substitute. The study’s aim is to evaluate the use, effectiveness, and safety of using small intestine submucosal extracellular matrix (SIS-ECM) patches in a congenital cardiac surgery program. MethodsThis is a single-center, retrospective, cohort study of surgeries using SIS-ECM between 2012 and 2019. The SIS-ECM data were categorized by use and type (four-ply and two-ply). All reinterventions and complications were reviewed by an independent surgeon, a practicing congenital heart surgeon, and a pediatric cardiologist. ResultsIn all, 408 SIS-ECM patches were used in 309 patients (188 male, 121 female; median age 8.5 months). Use of the patches consisted of 314 arterioplasties (77%), 22 venoplasties (5.4%), 63 intracardiac repairs (15.4%), and 9 valve repairs (2.2%). The most common use was for pulmonary artery repair (n = 181; 44.4%). Median follow-up time was 3.9 years (range, 3 days to 7.4 years). Ten patches (2.5%) required surgical reintervention (2 in the first 30 days and 5 in the first year) and 27 (6.6%) required percutaneous reinterventions (2 in the first 30 days and 22 in the first year). Between four-ply (n = 376) and two-ply (n = 32) SIS-ECM, the rate of surgical (2.1% [n = 8] vs 6.3% [n = 2], P = .18) or percutaneous reinterventions (6.4% [n = 24] vs 9.4% [n = 3], P = .46) was not different. There were no deaths related to the SIS-ECM patch or reports of calcification. ConclusionsThe SIS-ECM is a viable patch option that can be used in various cardiac and vascular reconstructive surgeries with low risk of failure and calcification. Long-term, positive outcomes may be maximized by using consistent techniques and understanding the appropriate applications of the patch.

Extracellular Matrix Patches for Endarterectomy Repair.

Patch repair is the preferred method for arteriotomy closure following femoral or carotid endarterectomy. Choosing among available patch options remains a clinical challenge, as current evidence suggests roughly comparable outcomes between autologous grafts and synthetic and biologic materials. Biologic patches have potential advantages over other materials, including reduced risk for infection, mitigation of an excessive foreign body response, and the potential to remodel into healthy, vascularized tissue. Here we review the use of decellularized extracellular matrix (ECM) for cardiovascular applications, particularly endarterectomy repair, and the capacity of these materials to remodel into native, site-appropriate tissues. Also presented are data from two post-market observational studies of patients undergoing iliofemoral and carotid endarterectomy patch repair as well as one histologic case report in a challenging iliofemoral endarterectomy repair, all with the use of small intestine submucosa (SIS)-ECM. In alignment with previously reported studies, high patency was maintained, and adverse event rates were comparable to previously reported rates of patch angioplasty. Histologic analysis from one case identified constructive remodeling of the SIS-ECM, consistent with the histologic characteristics of the endarterectomized vessel. These clinical and histologic results align with the biologic potential described in the academic ECM literature. To our knowledge, this is the first histologic demonstration of SIS-ECM remodeling into site-appropriate vascular tissues following endarterectomy. Together, these findings support the safety and efficacy of SIS-ECM for patch repair of femoral and carotid arteriotomy.

Long-term Results With CorMatrix Extracellular Matrix Patches After Carotid Endarterectomy

BackgroundPrevious reports of extracellular matrix (ECM) patch use after carotid endarterectomy (CEA) have noted an approximately 10% rate of pseudoaneurysm (PSA) formation. PSA-related rupture of ECM patches has also been described after femoral artery repair. In these studies, different thicknesses (4-ply versus 6-ply) and no standard length of soaking the patch in saline before implantation were used. Herein, we describe our experience with ECM CorMatrix patches in 291 CEAs with 6-ply patches. MethodsThe records of 275 consecutive patients undergoing 291 CEAs with CorMatrix 6-ply patches beginning in November of 2011 and extending until 2015 were reviewed. Only 6-ply patches and a 1 min hydration time in saline were used in all patients. No shunts were used. ResultsThere were three deaths within the first 30 d secondary to subsequent cardiac surgical procedures. Nine patients experienced a perioperative stroke (3.1%), only one of which occurred secondary to an occluded internal carotid artery. One patient had a transient ischemic attack with a patent endarterectomy site.In follow-up, 11 patients (4.5%) developed severe recurrent stenoses requiring reintervention. Only one patient (0.34%) developed a PSA at 2 years possibly secondary to chronic infection. The median follow-up was 72 mo. ConclusionsOur experience with 6-ply CorMatrix ECM patches and a brief period of soaking demonstrated that these patches performed well in patients requiring a CEA. Only one PSA was noted.

Clinical outcomes and structural integrity rate of arthroscopic augmented rotator cuff repairs using extracellular porcine matrix patch.

Structural failure rate in rotator cuff repairs is still high. The purpose of the study is to assess the structural integrity of a series of augmented rotator cuff repairs with porcine matrix patch and report the functional outcomes. Between 2014 and 2017, 44 consecutive patients underwent arthroscopic double-row repair of medium to massive rotator cuff tears with extracellular porcine dermal matrix augmentation. At one-year follow-up, magnetic resonance imaging scan was performed to assess the integrity of the repair. Oxford Shoulder Score (OSS), Constant Score (CS) and Visual Analogue Scale pain score, together with range of motion were used to assess patients. Patients mean age was 68 (53-82); mean follow-up was 17.2 (12-24) months. On magnetic resonance imaging scans, seven rotator cuff repair failures (15.9%) were observed: tear size was an independent predictor of re-rupture at one-year follow-up. Clinical scores showed a statistically significant improvement at three months and until final follow-up (p< 0.001). No complications occurred. Observed structural failure rate of 15.9% is lower than those reported in the literature for standard rotator cuff repair of medium to massive tears in similar cohorts to ours. Extracellular matrix augmentation for rotator cuff repair was shown to be a safe and reliable support to the repairs and patients recovered good shoulder function.Level of Evidence: Level IV.

Annular Dynamics and Leaflet Geometry in Patch Reconstruction of the Posterior Mitral Leaflet After Adding a Flexible Annuloplasty Ring.

Patch reconstruction of the posterior mitral leaflet using small intestinal submucosa extracellular matrix has been successfully performed in a porcine study. The patch reconstruction, however, resulted in non-physiological systolic widening of the mitral annulus, suggesting the need for an annuloplasty ring. The objective was to characterize the impact on annular dynamics and leaflet geometry of adding a flexible annuloplasty ring to the posterior mitral leaflet patch reconstruction. Measurements were performed in an acute 80-kg porcine model, with seven pigs acting as their own controls. The posterior mitral leaflet was reconstructed with a 2-ply small intestinal submucosa extracellular matrix patch (CorMatrix®). Additionally, a Simulus® Flexible Annuloplasty Ring (Medtronic Inc., Minneapolis, MN, USA) was inserted. Mitral annular dynamics were evaluated using sonomicrometry, and leaflet geometry was described using echocardiography. The annuloplasty ring reduced mitral annular dimensions and restricted cyclic changes in mitral annular area (126 ± 19 vs. 30 ± 13mm2, p < 0.001), septal-lateral and commisure-commisure distances. Ring annuloplasty prevented systolic widening in the mitral annulus after posterior mitral leaflet reconstruction. The annular saddle shape and leaflet coaptation length (8.7 ± 2.3 vs. 9.7 ± 1.3mm, p = 0.221) were comparable before and after ring insertion. The flexible annuloplasty ring resulted in a downsized annulus with restriction of cyclic annular changes in the reconstructed mitral valve. Ring insertion preserved the annular saddle shape and coaptation length. The ring annuloplasty counteracted the non-physiological annular dynamics, and this may improve durability of the posterior mitral leaflet patch reconstruction.

Rotator cuff repair with biological graft augmentation causes adverse tissue outcomes

Background and purpose — Biological patches can be used to augment rotator cuff tendon repair in an attempt to improve healing and reduce rates of re-rupture. However, little is known about the in vivo tissue response to these patches. We assessed native rotator cuff tissue response after surgical repair and augmentation with 2 commercially available extracellular matrix (ECM) patches. Patients and methods — Patients underwent a rotator cuff repair augmented with either GraftJacket (Wright Medical), Permacol (Zimmer Biomet), or no patch (Control), applied using an onlay technique. A sample of supraspinatus tendon was collected intraoperatively and 4 weeks post-surgery, using ultrasound-guided biopsy. Histology and immunohistochemistry were performed on all samples. Results — The Permacol group (n = 3) and GraftJacket group (n = 4) demonstrated some changes in native tendon ECM compared with the control group (n = 3). Significant disruption of the extracellular matrix of the repaired native supraspinatus, underlying both patches, was observed. The patches did not generally increase cellularity, foreign body giant cell count, or vascularity compared to the control group. 1 patient in the Permacol group had an adverse tissue immune response characterized by extensive infiltration of IRF5+, CD68+, and CD206+ cells, suggesting involvement of macrophages with a pro-inflammatory phenotype. No significant differences in protein expression of CD4, CD45, CD68, CD206, BMP7, IRF5, TGFß, and PDPN were observed among the groups. Interpretation — Histological and immunohistochemical analysis of native tendon tissue after patch augmentation in rotator cuff repair raises some concerns about a lack of benefit and potential for harm from these materials.

Mitral Valve Posterior Leaflet Reconstruction Using Extracellular Matrix: In Vitro Evaluation.

To investigate the anatomical and functional effects of complete surgical reconstruction of the posterior mitral leaflet and associated chordae tendineae with a patch made of 2-ply small intestinal submucosal extracellular matrix in vitro. Seven explanted mitral valves with intact subvalvular apparatus from 80-kg pigs were evaluated in a left heart simulator and served as their own controls. After testing the native valve, the mitral posterior leaflet and associated chordae tendineae were excised and reconstructed by using the 2-ply small intestinal submucosa extracellular matrix patch. The characterization of the reconstruction was based on geometric data from digital images, papillary muscle force, annular tethering force and leaflet pressure force. The reconstructed valves were fully functional without regurgitation, tearing or rupture during incrementally increased pressure from 0 to 120 mmHg. The leaflet areas were preserved after reconstruction, with a normal configuration of the coaptation line. However, the coaptation midpoint moved posteriorly after reconstruction (A2: 15.8 ± 1.4 vs. 18.9 ± 1.5 mm, p = 0.002, diff = 3.1 mm, 95% CI 1.3 to 4.8 mm). The anterior papillary muscle force increased significantly (3.9 vs. 4.6 N, p = 0.029, diff = 0.7 N, 95% CI 0.1 to 1.4 N at 120mmHg) after reconstruction. The posterior papillary muscle force, leaflet pressure force and annular pressure force did not change significantly. In this in vitro model, mitral valve anatomy and function were comparable between the native mitral valve and our new surgical technique for complete reconstruction of the posterior mitral leaflet and associated chordae tendineae. These promising results warrant further in vivo evaluation.

Novel ECM Patch Combines Poly(vinyl alcohol), Human Fibroblast-Derived Matrix, and Mesenchymal Stem Cells for Advanced Wound Healing.

Decellularized extracellular matrix (ECM)-based scaffold has been a very useful resource for effective tissue regeneration. In this study, we report a novel ECM patch that physically combines human fibroblast-derived matrix (hFDM) and poly(vinyl alcohol) (PVA) hydrogel. hFDM was obtained after decellularization of in vitro cultured human fibroblasts. We investigated the basic characteristics of hFDM alone using immunofluorescence (fibronectin, collagen type I) and angiogenesis-related factor analysis. Successful incorporation of hFDM with PVA produced an hFDM/PVA patch, which showed excellent cytocompatibility with human mesenchymal stem cells (hMSCs), as assessed via cell adhesion, viability, and proliferation. Moreover, in vitro scratch assay using human dermal fibroblasts showed a significant improvement of cell migration when treated with the paracrine factors originated from the hMSC-incorporated hFDM. To evaluate the therapeutic effect on wound healing, hMSCs were seeded on the hFDM/PVA patch and they were then transplanted into a mouse full-thickness wound model. Among four experimental groups (control, PVA, hFDM/PVA, hMSC/hFDM/PVA), we found that hMSC/hFDM/PVA patch accelerated the wound closure with time. More notably, histology and immunofluorescence demonstrated that compared to the other interventions tested, hMSC/hFDM/PVA patch could lead to significantly advanced tissue regeneration, as confirmed via nearly normal epidermis thickness, skin adnexa regeneration (hair follicle), mature collagen deposition, and neovascularization. Additionally, cell tracking of prelabeled hMSCs suggests the in vivo retention of transplanted cells in the wound region after the transplantation of hMSC/hFDM/PVA patch. Taken together, our engineered ECM patch supports a strong regenerative potential toward advanced wound healing.

Epicardial transplantation of atrial appendage micrograft patch salvages myocardium after infarction

Ischemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting, adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without delivering significant clinical benefits. We evaluated the effect of epicardially delivered minute pieces of atrial appendage tissue material, defined as atrial appendage micrografts (AAMs), in a mouse myocardial infarction model. An extracellular matrix patch was used to cover and fix the AAMs onto the surface of the infarcted heart. The matrix-covered AAMs salvaged the heart from the infarction-induced loss of functional myocardium and attenuated scarring. Site-selective proteomics of injured ischemic and uninjured distal myocardium from AAMs-treated and -untreated tissue sections revealed increased expression of several cardiac regeneration-associated proteins (i.e., periostin, transglutaminases, and glutathione peroxidases) and activation of pathways responsible for angiogenesis and cardiogenesis in relation to AAMs therapy. Epicardial delivery of AAMs encased in an extracellular matrix patch scaffold salvages functional cardiac tissue from ischemic injury and restricts fibrosis after myocardial infarction. Our results support the use of AAMs as tissue-based therapy adjuvants for salvaging the ischemic myocardium.

A Novel Ecm Patch Combines Human Fibroblast-Derived Matrix and Mesenchymal Stem Cells for Advanced Deep Wound Healing

Decellularized extracellular matrix (ECM)-based scaffold has been a very useful resource for effective tissue regeneration. In this study, we report a novel ECM patch that physically combines human fibroblast-derived matrix (hFDM) and polyvinyl alcohol (PVA) hydrogel. hFDM was obtained after decellularization of in vitro cultured human fibroblasts. We investigated the basic characteristics of hFDM itself using immunofluorescence (fibronectin, collagen type Ⅰ) and angiogenesis related factors analysis. Successful incorporation of hFDM with PVA produced an hFDM/PVA patch, which showed an excellent cytocompatibility with human mesenchymal stem cells (hMSCs), as assessed via cell adhesion, viability, and proliferation. Moreover, in vitro scratch assay using human dermal fibroblasts showed a significant improvement of cell migration when treated with the paracrine factors orignated from the hMSCs-incorporated hFDM. To evaluate therapeutic effect on wound healing, hMSCs were seeded on the hFDM/PVA patch and they were then transplanted into mouse full-thickness wound model. Among four experimental groups (control, PVA, hFDM/PVA, hMSC/hFDM/PVA), we found that hMSC/hFDM/PVA patch accelerated the wound closure with time. More notably, histology and immunofluorescence demonstrated that compared to normal skin tissue, hMSC/hFDM/PVA patch could lead to significantly advanced tissue regeneration, as confirmed via nearly normal epidermis thickness, skin adnexa regeneration (hair follicle), mature collagen deposition, and neovascularization. Additionally, cell tracking of pre-labelled hMSCs suggegsts the in vivo retention of transplanted cells in the wound region after transplantation of hMSC/hFDM/PVA patch. Taken together, our engineered ECM patch demonstrates a strong regeneration potential toward advanced wound healing.

Tissue-engineered human embryonic stem cell-containing cardiac patches: evaluating recellularization of decellularized matrix

Decellularized cardiac extracellular matrix scaffolds with preserved composition and architecture can be used in tissue engineering to reproduce the complex cardiac extracellular matrix. However, evaluating the extent of cardiomyocyte repopulation of decellularized cardiac extracellular matrix scaffolds after recellularization attempts is challenging. Here, we describe a unique combination of biochemical, biomechanical, histological, and physiological parameters for quantifying recellularization efficiency of tissue-engineered cardiac patches compared with native cardiac tissue. Human embryonic stem cell-derived cardiomyocytes were seeded into rat heart atrial and ventricular decellularized cardiac extracellular matrix patches. Confocal and atomic force microscopy showed cell integration within the extracellular matrix basement membrane that was accompanied by restoration of native cardiac tissue passive mechanical properties. Multi-electrode array and immunostaining (connexin 43) were used to determine synchronous field potentials with electrical coupling. Myoglobin content (~60%) and sarcomere length measurement (>45% vs 2D culture) were used to evaluate cardiomyocyte maturation of integrated cells. The combination of these techniques allowed us to demonstrate that as cellularization efficiency improves, cardiomyocytes mature and synchronize electrical activity, and tissue mechanical/biochemical properties improve toward those of native tissue.

Clinical and Radiological Outcomes of Large and Massive Rotator Cuff Tears Treated With Arthroscopic Augmented Rotator Cuff Repairs Using Extracellular Matrix Patch: Minimum 1-Year Follow Up

Clinical and Radiological Outcomes of Large and Massive Rotator Cuff Tears Treated With Arthroscopic Augmented Rotator Cuff Repairs Using Extracellular Matrix Patch: Minimum 1-Year Follow Up

Manufacturing considerations for producing and assessing decellularized extracellular matrix hydrogels.

Although several decellularized extracellular matrix (ECM) sheets or patches have been commercialized for use in the clinic, only one injectable decellularized ECM hydrogel, a decellularized myocardial matrix, has reached clinical trials. Consequently, very little information is available for established manufacturing standards or assessments of these materials. Here we present detailed methodology for investigating three parameters related to manufacturing optimization for a porcine derived skeletal muscle ECM hydrogel - animal-to-animal variability, bioburden reduction, and harvesting conditions. Results from characterization assays, including residual dsDNA content and sulfated glycosaminoglycan content, did not yield noteworthy differences amongst individual animals or following the addition of a bioburden reducing agent. However, the tissue collected under different harvesting conditions contained varying amounts of fat, and the protein compositions of the decellularized products differed, which could ultimately impact subsequent efficacy in vitro or in vivo. As decellularized ECM hydrogels continue to be evaluated for various applications, the differences between laboratory-scale and manufacturing-scale material batches should be thoroughly considered to avoid costly and timely optimization during scale-up.