Total meniscectomy for treating massive meniscal tears may lead to joint instability, cartilage degeneration, and even progressive osteoarthritis. The meniscal substitution strategies for advancing reconstruction of the meniscus deserve further investigation.
A decellularized meniscal scaffold (DMS) modified with collagen affinity stromal cell-derived factor (C-SDF1α) may facilitate meniscal regeneration and protect cartilage from abrasion.
Controlled laboratory study.
The authors first modified DMS with C-SDF1α to fabricate a new meniscal graft (DMS-CBD [collagen-binding domain]). Second, they performed in vitro studies to evaluate the release dynamics, biocompatibility, and differentiation inducibility (osteogenic, chondrogenic, and tenogenic differentiation) on human bone marrow mesenchymal stem cells. Using in vivo studies, they subjected rabbits that received medial meniscectomy to a transplantation procedure to implement their meniscal graft. At postoperative weeks 6 and 12, the meniscal regeneration outcomes and chondroprotective efficacy of the new meniscal graft were evaluated by macroscopic observation, histology, micromechanics, and immunohistochemistry tests.
In in vitro studies, the optimized DMS-CBD graft showed notable biocompatibility, releasing efficiency, and chondrogenic inducibility. In in vivo studies, the implanted DMS-CBD graft after total meniscectomy promoted the migration of cells and extracellular matrix deposition in transplantation and further facilitated meniscal regeneration and protected articular cartilage from degeneration.
The new meniscal graft (DMS-CBD) accelerated extracellular matrix deposition and meniscal regeneration and protected articular cartilage from degeneration.
The results demonstrate that the DMS-CBD graft can serve as a potential meniscal substitution after meniscectomy.

Decellularized extracellular matrix (dECM) is a promising material for tissue engineering applications. Tissue-specific dECM is often seen as a favorable material that recapitulates a native-like microenvironment for cellular remodeling. However, the minute quantity of dECM derivable from small organs like the vocal fold (VF) hampers manufacturing scalability. Small intestinal submucosa (SIS), a commercial product with proven regenerative capacity, may be a viable option for VF applications. This study aims to compare dECM hydrogels derived from SIS or VF tissue with respect to protein content and functionality using mass spectrometry-based proteomics and in vitro studies. Proteomic analysis reveals that VF and SIS dECM share 75% of core matrisome proteins. Although VF dECM proteins have greater overlap with native VF, SIS dECM shows less cross-sample variability. Following decellularization, significant reductions of soluble collagen (61%), elastin (81%), and hyaluronan (44%) are noted in VF dECM. SIS dECM contains comparable elastin and hyaluronan but 67% greater soluble collagen than VF dECM. Cells deposit more neo-collagen on SIS than VF-dECM hydrogels, whereas neo-elastin (~50 μg/scaffold) and neo-hyaluronan (~ 6 μg/scaffold) are comparable between the two hydrogels. Overall, SIS dECM possesses reasonably similar proteomic profile and regenerative capacity to VF dECM. SIS dECM is considered a promising alternative for dECM-derived biomaterials for VF regeneration.

Pericardial patches are currently used as reconstructive material in cardiac surgery for surgical treatment of cardiac septal defects. Autologous pericardial patches, either treated with glutaraldehyde or not, can be used as an alternative to synthetic materials or xenograft in congenital septal defects repair. The availability of an allogenic decellularized pericardium could reduce complication during and after surgery and could be a valid alternative. Decellularization of allogenic tissues aims at reducing the immunogenic reaction that might trigger inflammation and tissue calcification over time. The ideal graft for congenital heart disease repair should be biocompatible, mechanically resistant, non-immunogenic, and should have the ability to growth with the patients. The aim of the present study is the evaluation of the efficacy of a new decellularization protocol of homologous pericardium, even after cryopreservation. The technique has proven to be suitable as a tissue bank procedure and highly successful in the removal of cells and nucleic acids content, but also in the preservation of collagen and biomechanical properties of the human pericardium.

The rise of tissue-engineered biomaterials has introduced more clinically translatable models of disease, including three-dimensional (3D) decellularized extracellular matrix (dECM) hydrogels. Specifically, decellularized nerve hydrogels have been utilized to model peripheral nerve injuries and disorders in vitro; however, there lacks standardization in decellularization methods. Here, rat sciatic nerves of varying preparations were decellularized using previously established methods: sodium deoxycholate (SD)-based, 3-((3-cholamidopropyl)dimethylammonio)-1-propanesulfonate (CHAPS)-based, and apoptosis-mediated. These nerves were characterized for cellular debris removal, ECM retention, and low cytotoxicity with cultured Schwann cells. The best preparations of each decellularization method were digested into dECM hydrogels, and rheological characterization, gelation kinetics, and confocal reflectance imaging of collagen fibril assembly were performed. It was determined that the SD-based method with nerve epineurial removal best maintained the overall ECM composition and mechanical properties of physiological peripheral nerves while efficiently stripping the scaffolds of tissue-specific cells and debris. This method was then utilized as a culture platform for quiescent Schwann cells and cancer-nerve crosstalk. Hydrogel-embedded Schwann cells were found to have high viability and act in a more physiologically relevant manner than those cultured in monolayers, and the hydrogel platform allowed for the activation of Schwann cells following treatment with cancer secreted factors. These findings establish a standard for peripheral nerve decellularization for usage as a dECM hydrogel testbed for in vitro peripheral nerve disease modeling and may facilitate the development of treatments for peripheral nerve disease and injury.

In veterinary practice, numerous urological disorders that cause bladder dysfunction necessitate augmentation cystoplasty (AC). The purpose of this study is to evaluate the dog tunica vaginalis allograft (DTVA), sheep tunica vaginalis xenograft (STVX) and sheep tunica vaginalis decellularized extracellular matrix (STVDEM) as graft materials for urinary bladder (UB) reconstruction following a 45±5% cystectomy model in dogs. In this study, 18 adult apparently healthy mongrel dogs of both sexes were divided into three groups (6 dogs each): the DTVA group, the STVX group, and the STVDEM group. The evaluation of the AC in different groups was carried out using clinical, hematological, serum biochemical, urine, ultrasonographic, retrograde positive cystogram, and histopathological analysis all over the study period of 12 weeks. The dogs in all groups survived the procedures, except three dogs died from both STVX and DTVA groups. The mean bladder capacity indicated that the DTVA and STVX groups had regained 82.22% and 68.62%, respectively, of their preoperative baseline capacity. Interestingly, the STVDEM group\'s bladder capacity increased to 113.70%. Although histological analysis revealed that the three grafts successfully rebuilt the bladder wall, the STVDEM demonstrated well-organized and well-differentiated epithelial and muscular tissues that resembled, but were not identical to, native UB tissues. As a result, STVDEM is proposed as an ideal and potential acellular graft for UB reconstruction in dogs, whereas DTVA and STVX could be employed in emergencies requiring UB reconstruction.

BACKGROUND: Conflicting results from previous studies have led to dissent over whether surgical mesh is safe and effective in ventral hernia repair. A newer class of mesh known as a reinforced tissue matrix, combining a biologic scaffold and minimal polymer reinforcement, offers promise in reducing inflammatory response and increasing abdominal wall support. This study sought to assess the clinical utility of a reinforced tissue matrix (OviTex) in ventral hernia repair 12 months after implantation.
METHODS: This is a prospective, single-arm, multi-center study to evaluate the clinical performance of OviTex® 1S Permanent (OviTex) in the repair of primary or recurrent ventral hernias (VH) in consecutive patients (ClinicalTrials.gov/NCT03074474). The rate of surgical site occurrences (SSOs) was evaluated 90 days post-surgery as the primary endpoint. Hernia recurrence and the incidence of postoperative events were evaluated between three and 12 months as secondary endpoints. The incidence of other complications and patient-reported outcomes were also recorded.
RESULTS: Ninety-two (92) patients were enrolled in the study, of whom seventy-six (76) reached the 12-month follow-up. All patients were at least 18 years of age with a BMI of <40 kg/m2. Hernia defects were <20 × 20 cm, classified as class I-III according to the CDC wound classification system. Of the 76 patients who reached 12-month follow-up, twenty-six (34%) had previous VH repairs and thirteen (17%) had previous surgical infection. Sixty (79%) had factors known to increase the risk of recurrence. Twenty patients (26%) experienced SSOs, with ten (13%) requiring procedural intervention. Two of the 75 patients (2.7%) experienced a recurrence.
CONCLUSIONS: The low rate of hernia recurrence and SSOs requiring intervention illustrates the potential that reinforced tissue matrices, and OviTex 1S, in particular, have to improve outcomes in VH repairs. Follow-up to 24 months is ongoing.

Cartilage regeneration is a complex physiological process. Synovial macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury. Due to the contrasting differences and heterogeneity of macrophage, the phenotype of macrophages are the key determinants of the healing response after cartilage injury. Biomaterials derived from extracellular matrix have been used for the repair and reconstruction of a variety of tissues by modulating the host macrophage response. However, the immunomodulatory effect of decellularized cartilage extracellular matrix (ECM) on macrophages has not been elucidated. It is necessary to clarify the immunomodulatory properties of decellularized cartilage matrix (DCM) to guide the design of cartilage regeneration materials. Here, we prepared porcine articular cartilage derived DCM and determined the response of mouse bone marrow-derived macrophages (BMDMs) to the pepsin-solubilized DCM (PDCM) in vitro. Macrophages activated by the PDCM could promote bone marrow-derived mesenchymal stem cells (BMSCs) invasion, migration, proliferation, and chondrogenic differentiation. Then, we verified that early optimization of the immunomodulatory effects of the cell-free DCM scaffold using IL-4 in vivo could achieve good cartilage regeneration in a rat knee osteochondral defect model. Therefore, this decellularized cartilage ECM scaffold combined with accurate and active immunomodulatory strategies provides a new approach for the development of cartilage regeneration materials. STATEMENT OF SIGNIFICANCE: This work reports a decellularized cartilage extracellular matrix (DCM) scaffold combined with an accurate and active immunomodulatory strategy to improve cartilage regeneration. Our findings demonstrated that the pepsin-solubilized DCM (PDCM) activated bone marrow-derived macrophages to polarize to a constructive macrophage phenotype. These polarized macrophages promoted bone marrow-derived mesenchymal stem cell invasion, migration, proliferation, and chondrogenic differentiation. DCM scaffolds combined with early-stage intra-articular injection of IL-4 created a wound-healing microenvironment and improved cartilage regeneration in a rat knee osteochondral defect model.

There are limitations in current medications of articular cartilage injuries. Although injectable bioactive hydrogels are promising options, they have decreased biomechanical performance. Researchers should consider many factors when providing solutions to overcome these challenges. In this study, we created an injectable composite hydrogel from chitosan and human acellular cartilage extracellular matrix (ECM) particles. In order to enhance its mechanical properties, we reinforced this hydrogel with microporous microspheres composed of the same materials as the structural building blocks of the scaffold. Articular cartilage from human donors was decellularized by a combination of physical, chemical, and enzymatic methods. The decellularization efficiency was assessed by histological analysis and assessment of DNA content. We characterized the composite constructs in terms of storage modulus, gelation time, biocompatibility, and differentiation potential. The results showed that mechanical behavior increased with an increase in microsphere content. The sample that contained 10% microsphere had an enhanced storage modulus of up to 90 kPa. Biocompatibility and preliminary differentiation investigations revealed that this composite hydrogel might have potential benefits for cartilage tissue engineering.

Cell therapy with a variety of stem populations is increasingly being investigated as a promising regenerative strategy for cardiovascular (CV) diseases. Their combination with adequate scaffolds represents an improved therapeutic approach. Recently, several biomaterials were investigated as scaffolds for CV tissue repair, with decellularized extracellular matrices (dECMs) arousing increasing interest for cardiac tissue engineering applications. The aim of this study was to analyze whether dECMs support the cardiac differentiation of CardiopoieticAF stem cells. These perinatal stem cells, which can be easily isolated without ethical or safety limitations, display a high cardiac differentiative potential. Differentiation was previously achieved by culturing them on Matrigel, but this 3D scaffold is not transplantable. The identification of a new transplantable scaffold able to support CardiopoieticAF stem cell cardiac differentiation is pivotal prior to encouraging translation of in vitro studies in animal model preclinical investigations. Our data demonstrated that decellularized extracellular matrices already used in cardiac surgery (the porcine CorTMPATCH and the equine MatrixPatchTM) can efficiently support the proliferation and cardiac differentiation of CardiopoieticAF stem cells and represent a useful cellular scaffold to be transplanted with stem cells in animal hosts.

Two innovative reinforced biologic materials were studied in a non-human primate hernia repair model. The test articles, which combine layers of ovine decellularized extracellular matrix with minimal amounts of synthetic polymer, were evaluated for their biologic performance as measured by inflammatory response, healing kinetics, integration, and remodeling into functional host tissue. For comparison, seven clinically used biologic and synthetic meshes were also studied.
Animals were implanted with test articles in surgically created full-thickness midline abdominal wall defects, and evaluated macroscopically and histologically at 4, 12, and 24 weeks.
Macroscopically, biologics resorbed and remodeled into naturally appearing tissue; the reinforced biologics appeared similar, but remodeled earlier and were less prone to stretch. Synthetics developed a layer of reactive tissue above and separate from the contracted mesh structure. At early time points, the collagen networks of biologics and reinforced biologics were infiltrated by host cells primarily as a peripheral layer on the biologics. As early as 12 weeks, the collagen networks associated with the reinforced biologics remodeled into organized host collagen. By 24 weeks, both reinforced biologics and biologics had low levels of inflammation. In contrast, a foreign body response persisted at 24 weeks with the synthetics, which had developed less organized collagen, separate in space from the actual mesh.
The current study shows a favorable response to reinforced biologics, which were associated with an initial inflammatory response, resolving by later time points, followed by active remodeling, and the formation of new morphologically functional collagen.