Facile Stem Cell Delivery to Bone Grafts Enabled by Smart Shape Recovery and Stiffening of Degradable Synthetic Periosteal Membranes

Abstract

Delivering stem/progenitor cells via a degradable synthetic membrane to devitalized allogenic tissue graft surfaces presents a promising allograft-mediated tissue regeneration strategy. However, balancing degradability and bioactivity of the synthetic membrane with physical characteristics demanded for successful clinical translation is challenging. Here we design well-integrated composites of hydroxyapatite (HA) and amphiphilic poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PELGA) with tunable degradation rates that stiffen upon hydration and exhibit excellent shape recovery ability at body temperature for efficiently delivering skeletal progenitor cells around bone grafts. Unlike conventional degradable polymers that weaken upon wetting, these amphiphilic composites stiffened upon hydration as a result of enhanced PEG crystallization. HA-PELGA composite membranes support the attachment, proliferation and osteogenesis of rat periosteum derived cells (PDCs) in vitro, as well as the facile transfer of confluent cell sheets of green fluorescent protein labelled bone marrow stromal cells (GFP-BMSCs). With efficient shape memory behaviors around physiological temperature, the composite membranes could be programmed with a permanent tubular configuration, deformed into a flat temporary shape desired for cell seeding/cell sheet transfer, and triggered to wrap around a femoral bone allograft upon 37 °C saline rinse and subsequently stiffen. These properties combined make electrospun HA-PELGA promising smart synthetic periosteal membranes for augmenting allograft healing.

Electrospun Fibrous Architectures for Drug Delivery, Tissue Engineering and Cancer Therapy

“…Firstly, 3D structural scaffolds are implanted to maintain the geometrical integrity of the target tissue and provide the necessary support for cells to attach, proliferate and differentiate in the meanwhile . Another method is preparing and utilizing occlusive membranes for providing space maintenance, covering the diseased area, promoting the recruitment and growth of osteogenic cells and blocking the migration of competing soft tissue cells from overlying mucosa …”

“…Biomaterial‐associated bone tissue engineering refers to the construction of an artificial implant which can accelerate bone vascularization and mineralization, therefore resulting the reconstruction of injured or diseased bones . Kang et al proposed a novel therapeutic design which embedded and delivered two growth actors simultaneously in core–shell fibers in combination of mesoporous bioactive glass nanospheres (MBNs), which acted as drug carriers and meanwhile enhanced the apatite‐forming ability and mechanical properties of the scaffolds.…”

Biodegradable Shape Memory Polymers in Medicine

“…A potential advantage to these systems is the ability to conform to irregular sized defects in bone ( Figure ). BSMPs have also been utilized as support materials for bone grafts, including multifunctional materials that also deliver stem cells to augment healing . Importantly, the utility of several BSMP formulations was shown to be enhanced with additives or reactive moieties, without negatively influencing their shape memory behavior.…”

Synthesis and properties of shape memory polymers of LLA, TMC, and ε‐CL terpolymers

“…However, the recovery ratio is relatively low, and the recovery temperature is too high for the use in human body . Copolymerization of LLA with other lactones and cyclic carbonates, such as ε‐CL or TMC, is a strategy to decrease the glass transition temperature of PLLA and, as a consequence, to lower the recovery temperature of the material in shape memory applications . Additionally, incorporation of these monomers results in the composition, and properties of the shape memory polymers vary in a wide range.…”