1.1. Hydrogels for tissue engineering applicationsDesigning of biologically active scaffolds with optimalcharacteristics is one of the key factors for successful tissue engineering.Recently, hydrogels have received a considerable interest as leading candidatesfor engineered tissue scaffolds due to their unique compositional andstructural similarities to the natural extracellular matrix, in addition totheir desirable framework for cellular proliferation and survival. Morerecently, the ability to control the shape, porosity, surface morphology, andsize of hydrogel scaffolds has created new opportunities to overcome variouschallenges in tissue engineering such as vascularization, tissue architectureand simultaneous seeding of multiple cells.
This review provides an overview ofthe different types of hydrogels, the approaches that can be used to fabricatehydrogel matrices with specific features and the recent applications ofhydrogels in tissue engineering. Special attention was given to the variousdesign considerations for an efficient hydrogel scaffold in tissue engineering.Also, the challenges associated with the use of hydrogel scaffolds weredescribed.Effective antiosteopenia therapy can be achieved by designinglong-term protein/peptide drug delivery systems for bone trabecula restoration.Here we show that a complex of salmon calcitonin and oxidized calcium alginate(sCT-OCA) was prepared and loaded into a thermosensitive copolymer hydrogel forlong-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lacticacid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lacticacid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol–gel transition at bodytemperature. The sustained release of sCT from the in situ gelling system wasdetermined by both the degradation of the hydrogel and the decomposition of thesCT-OCA complex.
This system showed sustained effects in reducing serum calciumand bone trabecula reconstruction in the treatment of glucocorticoid-inducedosteopenia in rats for approximately 30 days after a single subcutaneousinjection, which may shed light on antiosteopenia therapy in the future.Biomimetic parathyroid regeneration with sustained release ofparathyroid hormone (PTH) into the blood stream is a considerable challenge inhypoparathyroidism treatment. We recently reported that tonsil-derivedmesenchymal stem cells (TMSCs), if these cells were both differentiated invitro before implantation and incorporated into a scaffold Matrigel, are a goodcell source for parathyroid regeneration in a parathyroidectomized (PTX) animalmodel. Here, we present a new strategy for improved clinical application thatenhances the sustained release of PTH by controlling mechanical stiffness usingin situ-forming gelatin-hydroxyphenyl propionic acid (GH) hydrogels (GHH).
Differentiated TMSCs (dTMSCs) embedded in a GHH with a strength of 4.4 kPaexhibited the best sustained release of PTH and were the most effective inhypoparathyroidism treatment, showing improved blood calcium homeostasis comparedwith Matrigel-embedded dTMSCs. Interestingly, undifferentiated control TMSCs(cTMSCs) also released PTH in a sustained manner if incorporated into GHH.Collectively, these findings may establish a new paradigm for parathyroidregeneration that could ultimately evolve into an improved clinicalapplication.Periodontitis is the most common cause of tooth loss and bonedestruction in adults worldwide. Human periodontal ligament stem cells(hPDLSCs) may represent promising new therapeutic biomaterials for tissueengineering applications.
Stromal precursor antigen-1 (STRO-1) has been shownto have roles in adherence, proliferation, and multipotency. Parathyroidhormone (PTH) has been shown to enhance proliferation in osteoblasts.Therefore, in this study, we aimed to compare the functions of STRO-1(+) andSTRO-1(?) hPDLSCs and to investigate the effects of PTH on the osteogeniccapacity of STRO-1(+) hPDLSCs in order to evaluate their potential applicationsin the treatment of periodontitis. Our data showed that STRO-1(+) hPDLSCsexpressed higher levels of the PTH-1 receptor (PTH1R) than STRO-1(?) hPDLSCs.In addition, intermittent PTH treatment enhanced the expression of PTH1R andosteogenesis-related genes in STRO-1(+) hPDLSCs.
PTH-treated cells also exhibitedincreased alkaline phosphatase activity and mineralization ability. Therefore,STRO-1(+) hPDLSCs represented a more promising cell resource for biomaterialsand tissue engineering applications. Intermittent PTH treatment improved thecapacity for STRO-1(+) hPDLSCs to repair damaged tissue and ameliorate thesymptoms of periodontitis.Diabetes mellitus (DM) and aging are associated with bone fragilityand increased fracture risk. Both (1–37) N- and (107–111) C-terminalparathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. Wehere aimed to evaluate and compare the efficacy of either PTHrP (1–37) or PTHrP(107–111) loaded into gelatin–glutaraldehyde-coated hydroxyapatite (HA–Gel)foams to improve bone repair of a transcortical tibial defect in aging ratswith or without DM, induced by streptozotocin injection at birth.
Diabetic oldrats showed bone structural deterioration compared to their age-matchedcontrols. Histological and ?-computerized tomography studies showed incompletebone repair at 4 weeks after implantation of unloaded Ha–Gel foams in thetranscortical tibial defects, mainly in old rats with DM. However, enhanceddefect healing, as shown by an increase of bone volume/tissue volume andtrabecular and cortical thickness and decreased trabecular separation, occurredin the presence of either PTHrP peptide in the implants in old rats with orwithout DM. This was accompanied by newly formed bone tissue around theosteointegrated HA-Gel implant and increased gene expression of osteocalcin andvascular endothelial growth factor (bone formation and angiogenic markers,respectively), and decreased expression of Sost gene, a negative regulator ofbone formation, in the healing bone area. Our findings suggest that localdelivery of PTHrP (1–37) or PTHrP (107–111) from a degradable implant is anattractive strategy to improve bone regeneration in aged and diabetic subjects.