New insight into functional limb regeneration: A to Z approaches

Limb/digit amputation is a common event in humans caused by trauma, medical illness, or surgery. Although the loss of a digit is not lethal, it affects quality of life and imposes high costs on amputees. In recent years, the increasing interest in limb regeneration has led to enhanced scientific knowledge. However, the limited ability to develop functional limb regeneration in the clinical setting suggests that a challenging issue remains in limb regeneration. Recently, the emergence of regenerative engineering is a promising field to address this challenge and close the gap between science and clinical applications. Cell signalling and molecular mechanisms involved in the limb regeneration process have been extensively studied; however, there is still insufficient data on cell therapy and tissue engineering for limb regeneration. In this review, we intend to focus on therapeutic approaches for limb regeneration that are closely related to gene, immune, and stem cell therapies, as well as tissue engineering approaches that take into consideration the peculiar developmental properties of the limbs. In addition, we attempt to identify the challenges of these strategies for limb regeneration studies in terms of clinical settings and as a road map to accomplish the goal of functional human limb regeneration.     

Esophagus adenocarcinoma in a young patient with celiac disease; Is celiac disease a predisposing factor for esophagus adenocarcinoma as well as squamous cell carcinoma?

We report a 36-year-old female with longstanding oily diarrhea and new-onset dysphagia that was diagnosed as celiac disease and esophagus adenocarcinoma. Celiac is a multisystemic autoimmune disease associated with a longstanding inflammatory process, especially in the gastrointestinal tract. This chronic inflammation may lead to a modest increase in neoplasia risk. There is a modest increased risk of malignancy in celiac disease, particularly adenocarcinoma and T-cell lymphoma of the small intestine and squamous cell carcinoma (SCC) of the esophagus, mouth, and pharynx. Although there is an association between SCC of the esophagus and celiac disease, there are no reports in the English literature about a relationship between celiac disease and esophageal adenocarcinoma. This case shows that as well as SCC, adenocarcinoma of the esophagus may also occur in patients with longstanding celiac disease.     

Controlled release from a mechanically-stimulated thermosensitive self-heating composite hydrogel

Temperature has been extensively explored as a trigger to control the delivery of a payload from environment-sensitive polymers. The need for an external heat source only allows limited spatiotemporal control over the delivery process. We propose a new approach by using the dissipative properties of a hydrogel matrix as an internal heat source when the material is mechanically loaded. The system is comprised of a highly dissipative hydrogel matrix and thermo-sensitive nanoparticles that shrink upon an increase in temperature. Exposing the hydrogel to a cyclic mechanical loading for a period of 5 min leads to an increase of temperature of the nanoparticles. The concomitant decrease in the volume of the nanoparticles increases the permeability of the hydrogel network facilitating the release of its payload. As a proof-of-concept, we showed that the payload of the hydrogel is released after 5–8 min following the initiation of the mechanical loading. This delivery method would be particularly suited for the release of growth factor as it has been shown that cell receptor to growth factor is activated 5–20 min following a mechanical loading.     

Effects of lathyritic drugs and lathyritic demineralized bone matrix on induced and sustained osteogenesis

Demineralized bone matrix was implanted in normal and lathyritic rats. At 2 weeks, the bone that formed in the lathyritic animals had an elevated alkaline phosphatase activity and a reduced calcium content compared with the controls. Four weeks after implantation, these biochemical parameters were reversed, with a decrease in alkaline phosphatase activity and an increase in calcium content to control levels. the histology of the recovered implants revealed new bone formation. Lathyritic demineralized bone matrix was prepared from bones of rats fed β-aminopropionitrile for 2 weeks (2-week BAPN-DBM) or 4 weeks (4-week BAPN-DBN), and was implanted in normal rats. Two weeks after implantation, both preparations of lathyritic demineralized bone matrix demonstrated early bone formation, although alkaline phosphatase activity and calcium content were reduced. By 4 weeks after implantation, no biochemical or histological evidence of bone formation remained at the site of the 4-week BAPN-DBM implants; continued but reduced bone formation was observed at the site of the 2-week BAPN-DBM implants. Reconstitution of inactivated normal demineralized bone matrix with the guanidine-soluble extracts restored the osteoinductive capacity. However, reconsistution of inactivated lathyritic demineralized bone matrix (4-week BAPN-DBM) failed to restore the osteoinductive capacity. These results indicate that the degree of crosslinking of the collagen matrix that acts as a carrier for osteoinductive proteins plays a key role in inducing and sustaining osteogenesis.     

Bone differentiation of marrow-derived mesenchymal stem cells using beta-tricalcium phosphate-alginate-gelatin hybrid scaffolds

The aim of the present study was to establish a 3D culture system for bone differentiation of mesenchymal stem cells (MSCs), using a new hybrid sponge. To manufacture the scaffold, a composite of beta-tricalcium phosphate-alginate-gelatin was prepared and cast as pellets of 1 cm diameter. The sponge was then fabricated by drying in freeze-dryer for 12 h. The porosity, mean pore size, compressive modulus and strength of the composite sponge fabricated in this study were 89.7%, 325.3 microm, 1.82 and 0.196 MPa, respectively. To establish a 3D culture system, the rat bone marrow-derived MSCs were suspended in 500 microl diluted collagen gel, loaded into the porous sponge and provided with medium with or without osteogenic supplements for 3 weeks. The day after loading, the cells appeared in the scaffold's internal spaces, where later some of them from either culture survived by anchoring on the surfaces. At the end of cultivation period, individually adhered cells from both cultures were observed to be replaced by cell aggregates, in which mineralized matrix was detected by alizarin red staining. Furthermore, RT-PCR analysis indicated that the bone-specific gene osteocalcin was expressed in cultures in both the presence and absence of the osteogenic supplements. Taken together, it seems that the studied scaffolds are cell-compatible and, more importantly, possess some osteo-inductive properties.     

Bremsstrahlung parameters of praseodymium-142 in different human tissues: a dosimetric perspective for 142Pr radionuclide therapy

Objective

Praseodymium-142 [T _1/2?=?19.12?h, $ E_{\beta^{-}}$ ?=?2.162?MeV (96.3%), E???=?1575?keV (3.7%)] is one of the ¹⁴¹Pr radioisotopes. Many studies have been attempted to assess the significance of usage ¹⁴²Pr in radionuclide therapy. In many studies, the dosimetric parameters of ¹⁴²Pr sources were calculated by modeling ¹⁴²Pr sources in the water phantom and scoring the energy deposited around it. However, the medical dosimetry calculations in water phantom consider Bremsstrahlung production, raising the question: ??How important is to simulate human tissues instead of using water phantom??? This study answers these questions by estimation of ¹⁴²Pr Bremsstrahlung parameters.

Methods

The Bremsstrahlung parameters of ¹⁴²Pr as therapeutic beta nuclides in different human tissues (adipose, blood, brain, breast, cell nucleus, eye lens, gastrointestinal tract, heart, kidney, liver, lung deflated, lymph, muscle, ovary, pancreas, cartilage, red marrow, spongiosa, yellow marrow, skin, spleen, testis, thyroid and different skeleton bones) were calculated by extending the national council for radiation protection model. The specific Bremsstrahlung constant (?? _Br), probability of energy loss by beta during Bremsstrahlung emission (P _Br) and Bremsstrahlung activity (A _release)_Br were estimated. It should be mentioned that Monte Carlo simulation was used for estimation of ¹⁴²Pr Bremsstrahlung activity based on the element compositions of different human tissues and the calculated exposures from the anthropomorphic phantoms.

Results

?? _Br for yellow marrow was smallest amount (1.1962?×?10^?3 C/kg-cm²/MBq-h) compared to the other tissues and highest for cortical bone (2.4764?×?10^?3 C/kg-cm²/MBq-h), and, overall, ?? _Br for skeletal tissues were greater than other tissues. In addition, ?? _Br breast was 1.8261?×?10^?3 C/kg-cm²/MBq-h which was greater than sacrum and spongiosa bones. Moreover, according to (A _release)_Br of ¹⁴²Pr, the patients receiving ¹⁴²Pr do not have to be hospitalized for radiation precautions and the Bremsstrahlung production does not prevent the therapy for outpatients.

Conclusion

However, modeling ¹⁴²Pr source in water phantom for simulation of ¹⁴²Pr source in soft tissues could be acceptable due to similarity of ?? _Br in water and soft tissues; this approximation is a gross computation in the mediums encompassing high atomic numbers. These data may be practical in the investigation of Bremsstrahlung absorbed dose where ¹⁴²Pr is involved in radionuclide therapy.