An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering

Abstract

The need for bone repair has increased as the population ages. Stem cell-scaffold approaches hold immense promise for bone tissue engineering. However, currently, preformed scaffolds for cell delivery have drawbacks including the difficulty to seed cells deep into the scaffold, and inability for injection in minimally invasive surgeries. Current injectable polymeric carriers and hydrogels are too weak for load-bearing orthopedic application. The objective of this study was to develop an injectable and mechanically-strong stem cell construct for bone tissue engineering. Calcium phosphate cement (CPC) paste was combined with hydrogel microbeads encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs). The hUCMSC-encapsulating composite paste was fully injectable under small injection forces. Cell viability after injection matched that in hydrogel without CPC and without injection. Mechanical properties of the construct matched the reported values of cancellous bone, and were much higher than previous injectable polymeric and hydrogel carriers. hUCMSCs in the injectable constructs osteodifferentiated, yielding high alkaline phosphatase, osteocalcin, collagen type I, and osterix gene expressions at 7 d, which were 50–70 fold higher than those at 1 d. Mineralization by the hUCMSCs at 14 d was 100-fold that at 1 d. In conclusion, a fully-injectable, mechanically-strong, stem cell-CPC scaffold construct was developed. The encapsulated hUCMSCs remained viable, osteodifferentiated, and synthesized bone minerals. The new injectable stem cell construct with load-bearing capability may enhance bone regeneration in minimally-invasive and other orthopedic surgeries.

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

“…To test the ability of the solubilized dNPs to be injected and still form a gel, the samples were ejected through a 30 gauge needle using a maximum force of <200 N, which is the maximum applied force for injection by hand [55]. After injection, the ability to thermally gel was tested by incubating for 45 minutes at 37°C.…”

Fast-Degradable Microbeads Encapsulating Human Umbilical Cord Stem Cells in Alginate for Muscle Tissue Engineering

“…49 A recent study fabricated alginate microbeads of approximately 200 mm for cell encapsulation; no microbead degradation or cell release was reported. 10 Therefore, compared to these previous studies, the uniqueness of the present study was that hUCMSCs were encapsulated in alginate-fibrin microbeads with several hundred mm in size suitable for injection, and the microbeads were then packed into a hydrogel matrix for muscle tissue engineering. This system significantly enhanced cell viability and myogenic differentiation, compared to the usual method of direct cell seeding into a hydrogel.…”

“…8,9 Several investigations have used human umbilical cord MSCs (hUCMSCs) for tissue engineering of bone and cartilage. [10][11][12][13] Only a few studies investigated hUCMSCs for muscle engineering by culturing on dishes, or injecting into animals. [14][15][16] To date, there has been no report on using a three-dimensional scaffold to seed hUCMSCs for myogenic differentiation.…”

“…The percentage of live cells = Number of live cells/(live cells + dead cells). 10 In addition, the spreading of the live cells was quantified. The maximal diameters of the live cells in the images were measured using ImageJ software (version 1.44p; NIH).…”

Refilling drug delivery depots through the blood

“…Alginate is biocompatible and nonimmunogenic and can be gelled under gentle conditions, allowing encapsulation of drugs or biological factors with minimal trauma. Additionally, alginate is readily chemically modified for cell adhesion or as a drug carrier (12)(13)(14) and has tunable degradation rates (15), and chemically modified forms of alginate are currently used clinically as a drug delivery vehicle for proteins that promote regeneration of mineralized tissue (16) and have been used as a carrier for transplanted cells (14,(17)(18)(19). Drug-eluting injectable alginate hydrogels were chosen due to their ability to be introduced into the body in a minimally invasive manner (14).…”