Bone transplantation is used to treat bone defects arising from trauma, disease, congenital deformity, or tumor resection. Bone is the second most transplanted tissue after blood; however, current bone transplantation methods involve certain disadvantages. For example, bone autografts (i.e., bone harvested from a patient to be treated) are of limited availability and incur donor site morbidity. Bone allografts (i.e., bone harvested from a person who is not the patient to be treated) carry a risk of disease transmission. With seven million bone fractures per year in the U.S., and musculoskeletal conditions costing $215 billion [1,2], new biomaterial treatments are needed.
Calcium phosphate cements (CPCs) can be molded and set in situ to form hydroxyapatite, they are highly osteoconductive, and they can be resorbed and replaced by new bone. Recent studies have developed CPC into a carrier for stem cell delivery to enhance bone regeneration. Stem cell-based tissue engineering has immense potential to regenerate damaged and diseased tissues [3-7].
Human bone marrow mesenchymal stem cells (hBMSCs) can differentiate into osteoblasts, adipocytes, chondrocytes, myoblasts, neurons, and fibroblasts [8-10]. hBMSCs can be harvested from a patient, expanded in culture, induced to differentiate, and combined with a scaffold to repair bone defects. However, harvesting of autogenous hBMSCs requires an invasive procedure. Moreover, autogenous hBMSCs display lower self-renewal potential with aging of the individual from whom the cells are obtained.
Human umbilical cord mesenchymal stem cells (hUCMSCs) have been used in tissue engineering [11-16]. Umbilical cords can provide an inexpensive and inexhaustible stem cell source, without the invasive procedure of hBMSCs, and without the controversies of embryonic stem cells (hESCs). hUCMSCs are primitive MSCs that exhibit a high plasticity and developmental flexibility and appear to cause no immunorejection in vivo [12]. hUCMSCs have been cultured on tissue culture plastic [13], polymer scaffolds [16], and calcium phosphate scaffolds for tissue engineering [17-19].
Calcium phosphate (CaP) scaffolds are important for bone repair because they are bioactive, mimic the bone minerals, and can bond to neighboring bone, in contrast to bioinert implants that can form undesirable fibrous capsules [20-22]. The CaP minerals provide a preferred substrate for cell attachment and expression of the osteoblast phenotype [23,24]. However, for pre-formed bioceramic scaffolds to fit into a bone cavity, a surgeon must machine the graft or carve the surgical site, leading to increases in bone loss, trauma, and surgical time [2]. Pre-formed scaffolds have other drawbacks, including the difficulty in seeding cells deeply into the scaffold and the inability to inject such scaffolds in minimally-invasive surgeries [2,10].
Injectable scaffolds for cell delivery are advantageous because they can: (i) shorten the surgical operation time; (ii) minimize the damaging effects of large muscle retraction; (iii) reduce postoperative pain and scar size; (iv) achieve rapid recovery; and (v) reduce cost. Various injectable hydrogel and polymer carriers can be used for stem cell delivery [10,25]. However, current injectable carriers cannot be used in load-bearing repairs [10,25], such as those required in bone. For example, hydrogel scaffolds do not possess the mechanical strength to be used in load bearing applications [25].
Mechanical properties of scaffolding materials are of crucial importance in regeneration of load-bearing tissues such as bone. Specifically, scaffolding materials must be able to withstand stresses to avoid scaffold fracture and to maintain scaffold structure to define the shape of the regenerated tissue. However, to date, an injectable, bioactive, and strong scaffold for stem cell encapsulation and bone engineering has not yet been developed.
Hydroxyapatite (HA) and other calcium phosphate (CaP) bioceramics are useful in hard tissue repair because of their excellent biocompatibility [5,8,10,20-24]. When implanted into an osseous site, bone bioactive materials such as HA and other CaP implants and coatings provide an ideal environment for cellular reaction and colonization by osteoblasts. This leads to a tissue response termed osteoconduction in which bone grows on and bonds to the implant, promoting a functional interface. These bioceramics are highly useful for bone repair. However, one drawback is that sintered HA implants are generally not resorbable. Another limitation is that these bioceramics are pre-forms that require machining and may leave gaps when fitted into a bone cavity.
In contrast to CaP bioceramics, calcium phosphate cements (CPCs) can self-set in the bone site with intimate adaptation to complex shapes, they can be easily contoured for esthetics in craniofacial repairs, and they are highly osteoconductive and bioresorbable [26-32]. CPCs can be injected or molded, and set in situ to form a bioactive scaffold that bonds to bone [26-29]. The first CPC was approved by the Food and Drug Administration (FDA) in 1996 for craniofacial repairs [26,30-32]. CPC has excellent osteoconductivity and can be replaced by new bone [30-32]. However, several previous studies showed that human stem cell attachment on CPC is relatively poor. Therefore, there is a need to improve the cell attachment to CPC to enhance bone repair efficacy.