Critical Thinking

1.1. a complex of salmon calcitonin and oxidized

1.1. 
Hydrogels for tissue engineering applications

Designing of biologically active scaffolds with optimal
characteristics is one of the key factors for successful tissue engineering.
Recently, hydrogels have received a considerable interest as leading candidates
for engineered tissue scaffolds due to their unique compositional and
structural similarities to the natural extracellular matrix, in addition to
their desirable framework for cellular proliferation and survival. More
recently, the ability to control the shape, porosity, surface morphology, and
size of hydrogel scaffolds has created new opportunities to overcome various
challenges in tissue engineering such as vascularization, tissue architecture
and simultaneous seeding of multiple cells. This review provides an overview of
the different types of hydrogels, the approaches that can be used to fabricate
hydrogel matrices with specific features and the recent applications of
hydrogels in tissue engineering. Special attention was given to the various
design considerations for an efficient hydrogel scaffold in tissue engineering.
Also, the challenges associated with the use of hydrogel scaffolds were
described.

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Effective antiosteopenia therapy can be achieved by designing
long-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 for
long-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lactic
acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic
acid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol–gel transition at body
temperature. The sustained release of sCT from the in situ gelling system was
determined by both the degradation of the hydrogel and the decomposition of the
sCT-OCA complex. This system showed sustained effects in reducing serum calcium
and bone trabecula reconstruction in the treatment of glucocorticoid-induced
osteopenia in rats for approximately 30 days after a single subcutaneous
injection, which may shed light on antiosteopenia therapy in the future.

Biomimetic parathyroid regeneration with sustained release of
parathyroid hormone (PTH) into the blood stream is a considerable challenge in
hypoparathyroidism treatment. We recently reported that tonsil-derived
mesenchymal stem cells (TMSCs), if these cells were both differentiated in
vitro before implantation and incorporated into a scaffold Matrigel, are a good
cell source for parathyroid regeneration in a parathyroidectomized (PTX) animal
model. Here, we present a new strategy for improved clinical application that
enhances the sustained release of PTH by controlling mechanical stiffness using
in situ-forming gelatin-hydroxyphenyl propionic acid (GH) hydrogels (GHH).
Differentiated TMSCs (dTMSCs) embedded in a GHH with a strength of 4.4 kPa
exhibited the best sustained release of PTH and were the most effective in
hypoparathyroidism treatment, showing improved blood calcium homeostasis compared
with 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 parathyroid
regeneration that could ultimately evolve into an improved clinical
application.

Periodontitis is the most common cause of tooth loss and bone
destruction in adults worldwide. Human periodontal ligament stem cells
(hPDLSCs) may represent promising new therapeutic biomaterials for tissue
engineering applications. Stromal precursor antigen-1 (STRO-1) has been shown
to have roles in adherence, proliferation, and multipotency. Parathyroid
hormone (PTH) has been shown to enhance proliferation in osteoblasts.
Therefore, in this study, we aimed to compare the functions of STRO-1(+) and
STRO-1(?) hPDLSCs and to investigate the effects of PTH on the osteogenic
capacity of STRO-1(+) hPDLSCs in order to evaluate their potential applications
in the treatment of periodontitis. Our data showed that STRO-1(+) hPDLSCs
expressed higher levels of the PTH-1 receptor (PTH1R) than STRO-1(?) hPDLSCs.
In addition, intermittent PTH treatment enhanced the expression of PTH1R and
osteogenesis-related genes in STRO-1(+) hPDLSCs. PTH-treated cells also exhibited
increased alkaline phosphatase activity and mineralization ability. Therefore,
STRO-1(+) hPDLSCs represented a more promising cell resource for biomaterials
and tissue engineering applications. Intermittent PTH treatment improved the
capacity for STRO-1(+) hPDLSCs to repair damaged tissue and ameliorate the
symptoms of periodontitis.

Diabetes mellitus (DM) and aging are associated with bone fragility
and increased fracture risk. Both (1–37) N- and (107–111) C-terminal
parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We
here 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 rats
with or without DM, induced by streptozotocin injection at birth. Diabetic old
rats showed bone structural deterioration compared to their age-matched
controls. Histological and ?-computerized tomography studies showed incomplete
bone repair at 4 weeks after implantation of unloaded Ha–Gel foams in the
transcortical tibial defects, mainly in old rats with DM. However, enhanced
defect healing, as shown by an increase of bone volume/tissue volume and
trabecular and cortical thickness and decreased trabecular separation, occurred
in the presence of either PTHrP peptide in the implants in old rats with or
without DM. This was accompanied by newly formed bone tissue around the
osteointegrated HA-Gel implant and increased gene expression of osteocalcin and
vascular endothelial growth factor (bone formation and angiogenic markers,
respectively), and decreased expression of Sost gene, a negative regulator of
bone formation, in the healing bone area. Our findings suggest that local
delivery of PTHrP (1–37) or PTHrP (107–111) from a degradable implant is an
attractive strategy to improve bone regeneration in aged and diabetic subjects.

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