Multi-component hybrid hydrogels – understanding the extent of orthogonal assembly and its impact on controlled release

This paper reports self-assembled multi-component hybrid hydrogels including a range of nanoscale systems and characterizes the extent to which each component maintains its own unique functionality, demonstrating that multi-functionality can be achieved by simply mixing carefully-chosen constituents. Specifically, the individual components are: (i) pH-activated low-molecular-weight gelator (LMWG) 1,3;2,4-dibenzylidenesorbitol-4′,4′′-dicarboxylic acid (DBS–COOH), (ii) thermally-activated polymer gelator (PG) agarose, (iii) anionic biopolymer heparin, and (iv) cationic self-assembled multivalent (SAMul) micelles capable of binding heparin. The LMWG still self-assembles in the presence of PG agarose, is slightly modified on the nanoscale by heparin, but is totally disrupted by the micelles. However, if the SAMul micelles are bound to heparin, DBS–COOH self-assembly is largely unaffected. The LMWG endows hybrid materials with pH-responsive behavior, while the PG provides mechanical robustness. The rate of heparin release can be controlled through network density and composition, with the LMWG and PG behaving differently in this regard, while the presence of the heparin binder completely inhibits heparin release through complexation. This study demonstrates that a multi-component approach can yield exquisite control over self-assembled materials. We reason that controlling orthogonality in such systems will underpin further development of controlled release systems with biomedical applications

Living Bacterial Sacrificial Porogens to Engineer Decellularized Porous Scaffolds

Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D) hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types

Clinical application of scaffolds for cartilage tissue engineering

The purpose of this paper is to review the basic science and clinical literature on scaffolds clinically available for the treatment of articular cartilage injuries. The use of tissue-engineered grafts based on scaffolds seems to be as effective as conventional ACI clinically. However, there is limited evidence that scaffold techniques result in homogeneous distribution of cells. Similarly, few studies exist on the maintenance of the chondrocyte phenotype in scaffolds. Both of which would be potential advantages over the first generation ACI. The mean clinical score in all of the clinical literature on scaffold techniques significantly improved compared with preoperative values. More than 80% of patients had an excellent or good outcome. None of the short- or mid-term clinical and histological results of these tissue-engineering techniques with scaffolds were reported to be better than conventional ACI. However, some studies suggest that these methods may reduce surgical time, morbidity, and risks of periosteal hypertrophy and post-operative adhesions. Based on the available literature, we were not able to rank the scaffolds available for clinical use. Firm recommendations on which cartilage repair procedure is to be preferred is currently not known on the basis of these studies. Randomized clinical trials and longer follow-up periods are needed for more widespread information regarding the clinical effectiveness of scaffold-based, tissue-engineered cartilage repair

Cartilage immunoprivilege depends on donor source and lesion location

The ability to repair damaged cartilage is a major goal of musculoskeletal tissue engineering. Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce. Immune rejection of non-autologous hyaline articular cartilage has seldom been considered due to the popular notion of “cartilage immunoprivilege.” The objective of this study was to determine the suitability of allogeneic and xenogeneic engineered neocartilage tissue for cartilage repair. To address this, scaffold-free tissue engineered articular cartilage of syngeneic (same genetic background), allogeneic, and xenogeneic origin were implanted into two different locations of the rabbit knee (n=3 per group/location). Xenogeneic engineered cartilage and control xenogeneic chondral explants provoked profound innate inflammatory and adaptive cellular responses, regardless of transplant location. Cytological quantification of immune cells showed that, while allogeneic neocartilage elicited an immune response in the patella, negligible responses were observed when implanted into the trochlea; instead the responses were comparable to microfracture-treated empty defect controls. Allogeneic neocartilage survived within the trochlea implant site and demonstrated graft integration into the underlying bone. In conclusion, the knee joint cartilage does not represent an immune privileged site, strongly rejecting xenogeneic but not allogeneic chondrocytes in a location-dependent fashion. This difference in location-dependent survival of allogeneic tissue may be associated with proximity to the synovium

Experimentelle Untersuchungen zur Reparatur von Gelenkknorpeldefekten durch Transplantation von stimulierten allogenen Chondrozyten Abschlussbericht

Available from TIB Hannover: DtF QN1(55,48) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman