Tissue-engineered Grafts Research Articles

Development of a regenerative porous PLCL nerve guidance conduit with swellable hydrogel-based microgrooved surface pattern via 3D printing

Peripheral nerve injury causes severe loss of motor and sensory functions, consequently increasing morbidity in affected patients. An autogenous nerve graft is considered the current gold standard for reconstructing nerve defects and recovering lost neurological functions; however, there are certain limitations to this method, such as limited donor nerve supply. With advances in regenerative medicine, recent research has focused on the fabrication of tissue-engineered nerve grafts as promising alternatives to the autogenous nerve grafts. In this study, we designed a nerve guidance conduit using an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane with a visible light-crosslinked gelatin hydrogel. The PLCL nanoporous membrane with permeability served as a flexible and non-collapsible epineurium for the nerve conduit; the inner-aligned gelatin hydrogel paths were fabricated via 3D printing and a photocrosslinking system. The resultant gelatin hydrogel with microgrooved surface pattern was established as a conducting guidance path for the effective regeneration of axons and served as a reservoir that can incorporate and release bioactive molecules. From in vivo performance tests using a rat sciatic nerve defect model, our PLCL/gelatin conduit demonstrated successful axonal regeneration, remyelination capacities and facilitated functional recovery. Hence, the PLCL/gelatin conduit developed in this study is a promising substitute for autogenous nerve grafts. Statement of significanceNerve guidance conduits (NGCs) are developed as promising recovery techniques for bridging peripheral nerve defects. However, there are still technological limitations including differences in the structures and components between natural peripheral nerve and NGCs. In this study, we designed a NGC composed of an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane and 3D printed inner gelatin hydrogel to serve as a flexible and non-collapsible epineurium and a conducting guidance path, respectively, to mimic the fascicular structure of the peripheral nerve. In particular, in vitro cell tests clearly showed that gelatin hydrogel could guide the cells and function as a reservoir that incorporate and release nerve growth factor. From in vivo performance tests, our regenerative conduit successfully led to axonal regeneration with effective functional recovery.

Pulmonary artery augmentation and aortic valve repair using novel tissue-engineered grafts.

ObjectivesThe objectives of this study were to evaluate the results when tissue-engineered vascular grafts (TEVGs) are used as alternatives to autologous pericardium for surgically augmenting the pulmonary artery (PA) or aortic valve.MethodsTEVG molds were embedded into subcutaneous spaces for more than 4 weeks preoperatively. Since 2014, 6 patients have undergone PA reconstruction, whereas 1 has undergone aortic valve plasty (AVP) with TEVGs. The time from mold implantation to the operation was 8.9 (range, 6.0-26.4) months. The age and body weight at the time of operation were 2.7 (range, 1.8-9.2) and 11.6 (range, 7.9-24.4) kg, respectively. Concomitant procedures comprised the Rastelli, palliative Rastelli, and Fontan operations in 2, 2, and 1 patient, respectively.ResultsThe median follow-up period was 14.4 (range, 3-39.6) months. There were no early or late mortalities. Moreover, there were no TEVG-related complications, including aneurysmal changes, degeneration, and infection. In 5 patients who underwent PA augmentation, the postoperative PA configuration was satisfactorily dilated. The reconstructed aortic valve function was good in the patient who underwent AVP. Decreased leaflet flexibility due to leaflet thickening was not observed. One patient had postoperative PA re-stenosis; therefore, re-PA augmentation with TEVGs was performed. On histological examination, TEVGs consisted of collagen fibers and few fibroblasts, and elastic fiber formation and/or smooth muscle cells were not observed.ConclusionsThe midterm results of PA reconstruction and AVP with TEVGs were satisfactory. TEVGs might be a useful alternative to autologous pericardium in pediatric cardiovascular surgeries that often require multistage operations.

Tissue-engineered composite tracheal grafts create mechanically stable and biocompatible airway replacements

We tested composite tracheal grafts (CTG) composed of a partially decellularized tracheal graft (PDTG) combined with a 3-dimensional (3D)-printed airway splint for use in long-segment airway reconstruction. CTG is designed to recapitulate the 3D extracellular matrix of the trachea with stable mechanical properties imparted from the extraluminal airway splint. We performed segmental orthotopic tracheal replacement in a mouse microsurgical model. MicroCT was used to measure graft patency. Tracheal neotissue formation was quantified histologically. Airflow dynamic properties were analyzed using computational fluid dynamics. We found that CTG are easily implanted and did not result in vascular erosion, tracheal injury, or inflammation. Graft epithelialization and endothelialization were comparable with CTG to control. Tracheal collapse was absent with CTG. Composite tracheal scaffolds combine biocompatible synthetic support with PDTG, supporting the regeneration of host epithelium while maintaining graft structure.

Engineering of Tracheal Grafts Based on Recellularization of Laser-Engraved Human Airway Cartilage Substrates.

ObjectiveImplantation of tissue-engineered tracheal grafts represents a visionary strategy for the reconstruction of tracheal wall defects after resections and may develop into a last chance for a number of patients with severe cicatricial stenosis. The use of a decellularized tracheal substrate would offer an ideally stiff graft, but the matrix density would challenge efficient remodeling into a living cartilage. In this study, we hypothesized that the pores of decellularized laser-perforated tracheal cartilage (LPTC) tissues can be colonized by adult nasal chondrocytes (NCs) to produce new cartilage tissue suitable for the repair of tracheal defects.DesignHuman, native tracheal specimens, isolated from cadaveric donors, were exposed to decellularized and laser engraving–controlled superficial perforation (300 μm depth). Human or rabbit NCs were cultured on the LPTCs for 1 week. The resulting revitalized tissues were implanted ectopically in nude mice or orthotopically in tracheal wall defects in rabbits. Tissues were assayed histologically and by microtomography analyses before and after implantation.ResultsNCs were able to efficiently colonize the pores of the LPTCs. The extent of colonization (i.e., percentage of viable cells spanning >300 μm of tissue depth), cell morphology, and cartilage matrix deposition improved once the revitalized constructs were implanted ectopically in nude mice. LPTCs could be successfully grafted onto the tracheal wall of rabbits without any evidence of dislocation or tracheal stenosis, 8 weeks after implantation. Rabbit NCs, within the LPTCs, actively produced new cartilage matrix.ConclusionImplantation of NC-revitalized LPTCs represents a feasible strategy for the repair of tracheal wall defects.

The application of tissue-engineered fish swim bladder vascular graft

Small diameter (< 6 mm) prosthetic vascular grafts continue to show very low long-term patency, but bioengineered vascular grafts show promising results in preclinical experiments. To assess a new scaffold source, we tested the use of decellularized fish swim bladder as a vascular patch and tube in rats. Fresh goldfish (Carassius auratus) swim bladder was decellularized, coated with rapamycin and then formed into patches or tubes for implantation in vivo. The rapamycin-coated patches showed decreased neointimal thickness in both the aorta and inferior vena cava patch angioplasty models. Rapamycin-coated decellularized swim bladder tubes implanted into the aorta showed decreased neointimal thickness compared to uncoated tubes, as well as fewer macrophages. These data show that the fish swim bladder can be used as a scaffold source for tissue-engineering vascular patches or vessels.

Fabrication of a Completely Biological and Anisotropic Human Mesenchymal Stem Cell-Based Vascular Graft.

Tissue-engineered small-diameter vascular grafts are required to match mechanical properties as well as cellular and extracellular architecture of native blood vessels. Although various engineering technologies have been developed, the most reliable strategy highlights the needs for incorporating completely biological components and anisotropic cellular and biomolecular organization into the tissue-engineered vascular graft (TEVG). Based on the antithrombogenic, immunoregulatory, and regenerative properties of human mesenchymal stem cells (hMSCs), this chapter provides a step-by-step protocol for generating a completely biological and anisotropic TEVG that comprises of hMSCs and highly aligned extracellular matrix (ECM) nanofibers. The hMSCs were grown on an aligned nanofibrous ECM scaffold derived from an oriented human dermal fibroblast (hDF) sheet and then wrapped around a temporary mandrel to form a tubular assembly, followed by a maturation process in a rotating wall vessel (RWV) bioreactor. The resulting TEVG demonstrates anisotropic structural and mechanical properties similar to that of native blood vessels. A completely biological, anisotropic, and mechanically strong TEVG that incorporates immunoregulatory hMSCs is promising to meet the urgent needs of a surgical intervention for bypass grafting.

Using fibrincollagen composite hydrogel and silk for bio-inspired design of tympanic membrane grafts: A vibro-acoustic analysis

Tympanic membrane (TM) is vulnerable to a variety of middle ear diseases. In some cases, reconstruction or repair of the TM is essential for recovering the hearing. Although there are many kinds of materials and therapeutics for TM reconstruction, tissue engineering of the TM is still in its initial steps of advancement. Treatment of damaged TM is usually carried out by otology-related techniques such as myringoplasty and tympanoplasty. Most of the novel tympanoplasty methods employ artificial grafts made of biomaterials and polymers for scaffolds. One biomaterial candidate for design and fabrication of synthetic grafts is spider silk, which has excellent mechanical and acoustic characteristics. On the other hand, the structural function of the spider web is also one of the potential inspirations for designing tissue-engineered grafts on micro-scale explorations. In this study, a bio-inspired design and analysis of silky TM grafts are carried out employing finite element modeling and vibro-acoustic investigation. A comparative and statistical analysis is also performed with experimentally validated data to check the suitability of the materials and design. The numerical study shows that the proposed bio-inspired models are appropriate for TM graft design and fabrication. The effects of inspired architecture and materials on obtaining an optimum design for TM grafts are put into evidence via a parametric study, and pertinent conclusions are outlined.

Chitin scaffold combined with autologous small nerve repairs sciatic nerve defects.

Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects, it has many clinical limitations. As an alternative, various tissue-engineered nerve grafts have been developed to substitute for autologous nerves. In this study, a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats. The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath, reduced atrophy of the target muscle, and effectively restored neurological function. When the epineurium of the small autogenous nerve was removed, the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation. These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds. The study was approved by the Research Ethics Committee of Peking University People's Hospital (approval No. 2019PHE27) on October 18, 2019.

Clinical, volumetric and densitometric evaluation of tissue engineered constructs for secondary alveolar cleft reconstruction: A randomized clinical trial

The objective of this study was to assess the efficacy of tissue engineered (TE) constructs compared to the standard autogenous anterior iliac crest (AIC) bone graft in secondary maxillary alveolar cleft reconstruction.This clinical trial was registered on (clinical trials.gov); the trial registry number is: NCT03563495. Patients with unilateral alveolar clefts were allocated on the basis of simple randomization. Selected patients were randomly divided into two equal groups: the AIC group (control) received autogenous particulate bone graft from anterior iliac crest, whereas the TE group received tissue engineered construct. Assessment included the newly formed bone volume and density at the grafted cleft sites, which were measured immediately, 6 and 12 months postoperatively on axial computed tomograms.The study population included 10 patients; each group comprised 5 patients. There was no statistically significant difference between the 2 groups regarding the mean volume of the newly formed bone (p = 0.91 at 6 months, p = 0.994 at 1 year) and the mean density of the newly formed bone (p = 0.364 at 6 months, p = 0.073 at 1 year). However, there was a significant increase of TE graft density from 6 months to 1 year (p = 0.048).Within the limitations of the study it seems that the tissue engineered construct (collagen/osteogenically differentiated bone marrow−derived mesenchymal stem cells) might be an alternative to autogenous bone for unilateral secondary alveolar cleftgrafting.

The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration.

Tissue-engineered nerve grafts (TENGs) are the most promising way for repairing long-distance peripheral nerve defects. Chitosan and poly (lactic-co-glycolic acid) (PLGA) scaffolds are considered as the promising materials in the pharmaceutical and biomedical fields especially in the field of tissue engineering. To further clarify the effects of a chitosan conduit inserted with various quantity of poly (lactic-co-glycolic acid) (PLGA) scaffolds, and their degrades on the peripheral nerve regeneration, the chitosan nerve conduit inserted with different amounts of PLGA scaffolds were used to repair rat sciatic nerve defects. The peripheral nerve regeneration at the different time points was dynamically and comprehensively evaluated. Moreover, the influence of different amounts of PLGA scaffolds on the regeneration microenvironment including inflammatory response and cell state were also revealed. The modest abundance of PLGA is more instrumental to the success of nerve regeneration, which is demonstrated in terms of the structure of the regenerated nerve, reinnervation of the target muscle, nerve impulse conduction, and overall function. The PLGA scaffolds aid the migration and maturation of Schwann cells. Furthermore, the PLGA and chitosan degradation products in a correct ratio neutralize, reducing the inflammatory response and enhancing the regeneration microenvironment. The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration. The findings represent a further step towards programming TENGs construction, applying polyester materials in regenerative medicine, and understanding the neural regeneration microenvironment.

First-in-Human Segmental Esophageal Reconstruction Using a Bioengineered Mesenchymal Stromal Cell–Seeded Implant

IntroductionResection and reconstruction of the esophagus remains fraught with morbidity and mortality. Recently, data from a porcine reconstruction model revealed that segmental esophageal reconstruction using an autologous mesenchymal stromal cell-seeded polyurethane graft (Cellspan esophageal implant [CEI]) can facilitate esophageal regrowth and regeneration. To this end, a patient requiring a full circumferential esophageal segmental reconstruction after a complex multiorgan tumor resection was approved for an investigational treatment under the Food and Drug Administration Expanded Access Use (Investigational New Drug 17402). MethodsAutologous adipose-derived mesenchymal stromal cells (Ad-MSCs) were isolated from the Emergency Investigational New Drug patient approximately 4 weeks before surgery from an adipose tissue biopsy specimen. The Ad-MSCs were grown and expanded under current Good Manufacturing Practice manufacturing conditions. The cells were then seeded onto a polyurethane fiber mesh scaffold (Cellspan scaffold) and cultured in a custom bioreactor to manufacture the final CEI graft. The cell-seeded scaffold was then shipped to the surgical site for surgical implantation. After removal of a tumor mass and a full circumferential 4 cm segment of the esophagus that was invaded by the tumor, the CEI was implanted by suturing the tubular CEI graft to both ends of the remaining native esophagus using end-to-end anastomosis. ResultsIn this case report, we found that a clinical-grade, tissue-engineered esophageal graft can be used for segmental esophageal reconstruction in a human patient. This report reveals that the graft supports regeneration of the esophageal conduit. Histologic analysis of the tissue postmortem, 7.5 months after the implantation procedure, revealed complete luminal epithelialization and partial esophageal tissue regeneration. ConclusionsAutologous Ad-MSC seeded onto a tubular CEI tissue-engineered graft stimulates tissue regeneration following implantation after a full circumferential esophageal resection.

Design and Fabrication of Sodium Alginate/Carboxymethyl Cellulose Sodium Blend Hydrogel for Artificial Skin.

Tissue-engineered skin grafts have long been considered to be the most effective treatment for large skin defects. Especially with the advent of 3D printing technology, the manufacture of artificial skin scaffold with complex shape and structure is becoming more convenient. However, the matrix material used as the bio-ink for 3D printing artificial skin is still a challenge. To address this issue, sodium alginate (SA)/carboxymethyl cellulose (CMC-Na) blend hydrogel was proposed to be the bio-ink for artificial skin fabrication, and SA/CMC-Na (SC) composite hydrogels at different compositions were investigated in terms of morphology, thermal properties, mechanical properties, and biological properties, so as to screen out the optimal composition ratio of SC for 3D printing artificial skin. Moreover, the designed SC composite hydrogel skin membranes were used for rabbit wound defeat repairing to evaluate the repair effect. Results show that SC4:1 blend hydrogel possesses the best mechanical properties, good moisturizing ability, proper degradation rate, and good biocompatibility, which is most suitable for 3D printing artificial skin. This research provides a process guidance for the design and fabrication of SA/CMC-Na composite artificial skin.

Tissue-Engineered Carotid Artery Interposition Grafts Demonstrate High Primary Patency and Promote Vascular Tissue Regeneration in the Ovine Model.

Tissue-engineered vascular graft for the reconstruction of small arteries is still an unmet clinical need, despite the fact that a number of promising prototypes have entered preclinical development. Here we test Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)Poly(ε-caprolactone) 4-mm-diameter vascular grafts equipped with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and stromal cell-derived factor 1α (SDF-1α) and surface coated with heparin and iloprost (PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo, n = 8) in a sheep carotid artery interposition model, using biostable vascular prostheses of expanded poly(tetrafluoroethylene) (ePTFE, n = 5) as a control. Primary patency of PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts was 62.5% (5/8) at 24 h postimplantation and 50% (4/8) at 18 months postimplantation, while all (5/5) ePTFE conduits were occluded within the 24 h after the surgery. At 18 months postimplantation, PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts were completely resorbed and replaced by the vascular tissue. Regenerated arteries displayed a hierarchical three-layer structure similar to the native blood vessels, being fully endothelialised, highly vascularised and populated by vascular smooth muscle cells and macrophages. The most (4/5, 80%) of the regenerated arteries were free of calcifications but suffered from the aneurysmatic dilation. Therefore, biodegradable PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts showed better short- and long-term results than bio-stable ePTFE analogues, although these scaffolds must be reinforced for the efficient prevention of aneurysms.

Fresh Osteochondral and Chondral Allograft Preservation and Storage Media: A Systematic Review of the Literature

Background: Storage procedures and parameters have a significant influence on the health of fresh osteochondral allograft (OCA) cartilage. To date, there is a lack of agreement on the optimal storage conditions for OCAs. Purpose: To systematically review the literature on (1) experimental designs and reporting of key variables of ex vivo (laboratory) studies, (2) the effects of various storage solutions and conditions on cartilage health ex vivo, and (3) in vivo animal studies and human clinical studies evaluating the effect of fresh OCA storage on osteochondral repair and outcomes. Study Design: Systematic review; Level of evidence, 5. Methods: A systematic review was performed using the PubMed, Embase, and Cochrane databases. The inclusion criteria were laboratory studies (ex vivo) reporting cartilage health outcomes after prolonged storage (>3 days) of fresh osteochondral or chondral tissue explants and animal studies (in vivo) reporting outcomes of fresh OCA. The inclusion criteria for clinical studies were studies (>5 patients) that analyzed the relationship of storage time or chondrocyte viability at time of implantation to patient outcomes. Frozen, cryopreserved, decellularized, synthetic, or tissue-engineered grafts were excluded. Results: A total of 55 peer-reviewed articles met the inclusion criteria. Ex vivo studies reported a spectrum of tissue sources and storage solutions and conditions, although the majority of studies lacked complete reporting of key variables, including storage solution formula and environmental conditions. The effect of various conditions (eg, temperature) and storage solutions on cartilage health were inconsistent. Although 60% of animal models suggest that storage time may influence outcomes and 80% indicate inferior outcomes with frozen OCA as compared with fresh OCA, 75% of clinical studies report no correlation between storage time and outcomes. Conclusion: Given the variability in experimental designs and lack of reporting across studies, it is still not possible to determine optimal storage conditions, although animal studies suggest that storage time and chondrocyte viability influence osteochondral repair outcomes. A list of recommendations was developed to encourage reporting of key variables, such as media formulation, environmental factors, and methodologies used. High-quality clinical data are needed to investigate the effects of storage and graft health on outcomes.

Epicardially Placed Bioengineered Cardiomyocyte Xenograft in Immune-Competent Rat Model of Heart Failure.

Background Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. In a previous study, tissue-engineered cardiac grafts were found to improve hosts' cardiac electrical and mechanical functions. However, the durability of effect, immune response, and in vitro properties of the tissue graft remained uncharacterized. This present study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing evaluation of the in vitro properties of the tissue graft. Methods hiPSC-CMs and human dermal fibroblasts were cultured into a synthetic bioabsorbable scaffold. The engineered grafts underwent epicardial implantation in infarcted immune-competent male Sprague-Dawley rats. Plasma samples were collected throughout the study to quantify antibody titers. At the study endpoint, all cohorts underwent echocardiographic, hemodynamic, electrophysiologic, and histopathologic assessments. Results The epicardially placed tissue graft therapy improved (p < 0.05) in vivo and ex vivo cardiac function compared to the untreated CHF cohort. Total IgM and IgG increased for both the untreated and graft-treated CHF cohorts. An immune response to the grafts was detected after seven days in graft-treated CHF rats only. In vitro, engineered grafts exhibited responsiveness to beta-adrenergic receptor agonism/antagonism and SERCA inhibition and elicited complex molecular profiles. Conclusions This hiPSC-CM-derived cardiac graft improved systolic and diastolic cardiac function in immune-competent CHF rats. The improvements were detectable at seven weeks post-graft implantation despite an antibody response beginning at week one and peaking at week three. This suggests that non-integrating cell-based therapy delivered by a bioengineered tissue graft for ischemic cardiomyopathy is a viable treatment option.

Three-Dimensional Tissue-Engineered Grafts for Hair Follicle Regeneration.

*New York University School of Medicine, New York, New York †Department of Dermatology, Weill Cornell Medicine, New York, New York The authors have indicated no significant interest with commercial supporters.

Material advancement in tissue-engineered nerve conduit

Abstract Peripheral nerve injuries resulting from various traumatic events can cause mobility problems and sensory impairment, jeopardizing patients’ life quality and bringing serious economic burdens. Due to the shortcomings of autologous nerve grafts, such as limited tissue sources, unmatched size, and loss of innervation at the donor site, tissue-engineered nerve grafts using both natural and synthetic materials have been employed in the treatment of peripheral nerve defect and to promote nerve regeneration. Apart from traditional advantages such as good biocompatibility and controllable degradation, the development of fabrication technology and the advancement in material science have endowed tissue-engineered nerve conduits with upgraded properties such as biomimetic surface topography, extracellular matrix components, neurotrophic factors, and cell seeding, or a conduit with micropores on the surface for substance exchange and/or with fillers inside for microenvironment simulation. This article reviews recent progress in the biomaterials employed in fabricating tissue-engineered nerve conduits, in vitro characterization, and their applications in nerve repair in animal studies as well as in clinical trials.

Tracheal Macrophages During Regeneration and Repair of Long-Segment Airway Defects.

Tissue-engineered tracheal grafts (TETGs) offer a potential solution for repair of long-segment airway defects. However, preclinical and clinical TETGs have been associated with chronic inflammation and macrophage infiltration. Macrophages express great phenotypic heterogeneity (generally characterized as classically activated [M1] vs. alternatively activated [M2]) and can influence tracheal repair and regeneration. We quantified and characterized infiltrating host macrophages using mouse microsurgical tracheal replacement models. Translational research, animal model. We assessed macrophage infiltration and phenotype in animals implanted with syngeneic tracheal grafts, synthetic TETGs, or partially decellularized tracheal scaffolds (DTSs). Macrophage infiltration was observed following tracheal replacement with syngeneic trachea. Both M1 and M2 macrophages were present in native trachea and increased during early tracheal repair (P= .014), with an M1/M2 ratio of 0.48 ± 0.15. In contrast, orthotopic implantation of synthetic TETGs resulted in a shift to M1 predominant macrophage phenotype with an increased M1/M2 ratio of 1.35 ± 0.41 by 6 weeks following implant (P= .035). Modulation of the synthetic scaffold with the addition of polyglycolic acid (PGA) resulted in a reduction of M1/M2 ratio due to an increase in M2 macrophages (P= .006). Using systemic macrophage depletion, the M1/M2 ratio reverted to native values in synthetic TETG recipients and was associated with an increase in graft epithelialization. Macrophage ratios seen in DTSs were similar to native values. M1 and M2 macrophages are present during tracheal repair. Poor epithelialization with synthetic TETG is associated with an elevation of the M1/M2 ratio. Macrophage phenotype can be altered with scaffold composition and host-directed systemic therapies. DTSs exhibit M1/M2 ratios similar to those seen in native trachea and syngeneic tracheal replacement. NA Laryngoscope, 132:737-746, 2022.

Reproducing the Biomechanical Environment of the Chondrocyte for Cartilage Tissue Engineering.

It is well known that the biomechanical and tribological performance of articular cartilage is inextricably linked to its extracellular matrix (ECM) structure and zonal heterogeneity. Furthermore, it is understood that the presence of native ECM components, such as collagen II and aggrecan, promote healthy homeostasis in the resident chondrocytes. What is less frequently discussed is how chondrocyte metabolism is related to the extracellular mechanical environment, at both the macro and microscale. The chondrocyte is in immediate contact with the pericellular matrix of the chondron, which acts as a mechanocoupler, transmitting external applied loads from the ECM to the chondrocyte. Therefore, components of the pericellular matrix also play essential roles in chondrocyte mechanotransduction and metabolism. Recreating the biomechanical environment through tuning material properties of a scaffold and/or the use of external cyclic loading can induce biosynthetic responses in chondrocytes. Decellularized scaffolds, which retain the native tissue macro- and microstructure also represent an effective means of recapitulating such an environment. The use of such techniques in tissue engineering applications can ensure the regeneration of skeletally mature articular cartilage with appropriate biomechanical and tribological properties to restore joint function. Despite the pivotal role in graft maturation and performance, biomechanical and tribological properties of such interventions is often underrepresented. This review outlines the role of biomechanics in relation to native cartilage performance and chondrocyte metabolism, and how application of this theory can enhance the future development and successful translation of biomechanically relevant tissue engineering interventions. Impact statement Physiological cartilage function is a key criterion in the success of a cartilage tissue engineering solution. The in situ performance is dependent on the initial scaffold design as well as extracellular matrix deposition by endogenous or exogenous cells. Both biological and biomechanical stimuli serve as key regulators of cartilage homeostasis and maturation of the resulting tissue-engineered graft. An improved understanding of the influence of biomechanics on cellular function and consideration of the final biomechanical and tribological performance will help in the successful development and translation of tissue-engineered grafts to restore natural joint function postcartilage trauma or osteoarthritic degeneration, delaying the requirement for prosthetic intervention.

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

The creation of small-diameter tissue-engineered vascular grafts using biodegradable materials has the potential to change the quality of cardiovascular surgery in the future. The implantation of these tissue-engineered arterial grafts has yet to reach clinical application. One of the reasons for this is thrombus occlusion of the graft in the acute phase. In this paper, we first describe the causes of accelerated thrombus formation and discuss the drugs that are thought to inhibit thrombus formation. We then review the latest research on methods to locally bind the anticoagulant heparin to biodegradable materials and methods to extend the duration of sustained heparin release. We also discuss the results of studies using large animal models and the challenges that need to be overcome for future clinical applications.