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1.
Biomed Mater ; 17(6)2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36044886

RESUMO

Hyaluronic acid (HA) hydrogels have been used for a multitude of applications, perhaps most notably for tissue engineering and regenerative medicine, owing to the versatility of the polymer and its tunable nature. Various groups have investigated the impact of hydrogel parameters (e.g. molecular weight, concentration, stiffness, etc)in vitroandin vivoto achieve desired material performance characteristics. A limitation in the literature to date has been that altering one hydrogel parameter (a 'manipulated variable') to achieve a given hydrogel characteristic (a 'controlled variable') changes two variables at a time (e.g. altering molecular weight and/or concentration to investigate cell response to stiffness). Therefore, if cell responses differ, it may be possible that more than one variable caused the changes in observed responses. In the current study, we leveraged thiol-ene click chemistry with a crosslinker to develop a method that minimizes material performance changes and permitted multiple material properties to be independently held constant to evaluate a single variable at a time. Independent control was accomplished by tuning the concentration of crosslinker to achieve an effectively constant stiffness for different HA hydrogel molecular weights and polymer concentrations. Specific formulations were thereby identified that enabled the molecular weight (76-1550 kDa), concentration (2%-10%), or stiffness (∼1-350 kPa) to be varied while the other two were held constant, a key technical achievement. The response of rat mesenchymal stem cells to varying molecular weight, concentration, and stiffness demonstrated consistent upregulation of osteocalcin gene expression. The methodology presented to achieve independent control of hydrogel parameters may potentially be adopted by others for alternative hydrogel polymers, cell types, or cell culture medium compositions to minimize confounding variables in experimental hydrogel designs.


Assuntos
Ácido Hialurônico , Hidrogéis , Animais , Condrogênese , Ácido Hialurônico/química , Hidrogéis/química , Peso Molecular , Polímeros , Ratos
2.
Acta Biomater ; 104: 66-75, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31904561

RESUMO

Bone regeneration of large cranial defects, potentially including traumatic brain injury (TBI) treatment, presents a major problem with non-crosslinking, clinically available products due to material migration outside the defect. Commercial products such as bone cements are permanent and thus not conducive to bone regeneration, and typical commercial bioactive materials for bone regeneration do not crosslink. Our previous work demonstrated that non-crosslinking materials may be prone to material migration following surgical placement, and the current study attempted to address these problems by introducing a new hydrogel system where tissue particles are themselves the crosslinker. Specifically, a pentenoate-modified hyaluronic acid (PHA) polymer was covalently linked to thiolated tissue particles of demineralized bone matrix (TDBM) or devitalized tendon (TDVT), thereby forming an interconnected hydrogel matrix for calvarial bone regeneration. All hydrogel precursor solutions exhibited sufficient yield stress for surgical placement and an adequate compressive modulus post-crosslinking. Critical-size calvarial defects were filled with a 4% PHA hydrogel containing 10 or 20% TDBM or TDVT, with the clinical product DBXⓇ being employed as the standard of care control for the in vivo study. At 12 weeks, micro-computed tomography analysis demonstrated similar bone regeneration among the experimental groups, TDBM and TDVT, and the standard of care control DBXⓇ. The group with 10% TDBM was therefore identified as an attractive material for potential calvarial defect repair, as it additionally exhibited a sufficient initial recovery after shearing (i.e., > 80% recovery). Future studies will focus on applying a hydrogel in a rat model for treatment of TBI. STATEMENT OF SIGNIFICANCE: Non-crosslinking materials may be prone to material migration from a calvarial bone defect following surgical placement, which is problematic for materials intended for bone regeneration. Unfortunately, typical crosslinking materials such as bone cements are permanent and thus not conducive to bone regeneration, and typical bioactive materials for bone regeneration such as tissue matrix are not crosslinked in commercial products. The current study addressed these problems by introducing a new biomaterial where tissue particles are themselves the crosslinker in a hydrogel system. The current study successfully demonstrated a new material based on pentenoate-modified hyaluronic acid with thiolated demineralized bone matrix that is capable of rapid crosslinking, with desirable paste-like rheology of the precursor material for surgical placement, and with bone regeneration comparable to a commercially available standard-of-care product. Such a material may hold promise for a single-surgery treatment of severe traumatic brain injury (TBI) following hemicraniectomy.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/fisiologia , Ácido Hialurônico/farmacologia , Hidrogéis/farmacologia , Crânio/fisiologia , Compostos de Sulfidrila/farmacologia , Tendões/fisiologia , Idoso , Animais , Osso e Ossos/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Reologia , Tendões/efeitos dos fármacos
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