Tissue engineering and regenerative medicine in musculoskeletal oncology

Abstract

Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.

Nanostructured Biomaterials for Bone Regeneration

“…For example, the bone healing deficiencies observed in older patients or smokers may require cell-based approaches or growth factors such as rhBMP-2, which may reliably stimulate healing but can be associated with significant adverse effects. Another example is the use of biologics, which is a strategy of choice in several orthopedic procedures, but that remains inappropriate in oncologic patients, where this may potentially exert local or even systemic tumor-promoting effects (Serakinci et al, 2014;Holzapfel et al, 2016). Together, these influences act through a variety of mechanisms to predispose some patients to impaired bone regeneration, which can only be overcome by personalized regenerative strategies.…”

miR-34a promotes bone regeneration in irradiated bone defects by enhancing osteoblastic differentiation of mesenchymal stromal cells in rats

“…Reconstruction of the bone defect after malignant tumor resection is difficult as the healing processes are influenced by the tumor and the treatment strategies including surgery, radiotherapy, or chemotherapy [3]. The regenerative medicine strategies of using stem cells, growth factors, and biomaterials to treat bone defects after tumor resection remain controversial for their potential tumor-promoting effects.…”

“…The resection of tumors can result in extensive bone defects, and reconstruction of the defect is needed [2]. However, radiotherapy hampers wound healing during bone reconstruction and restoration [3], which lead to higher rates of flap losses [4] and implant failures [5] in patients with radiotherapy.…”

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

“…In tissue engineering and regenerative medicine, many implantable biomaterials have been designed with good biocompatibility and osteoconductive ability to promote bone tissue regeneration (Sarigol-Calamak & Hascicek, 2018;Martin & Bettencourt, 2018). Calcium phosphate (Lee et al, 2016), CS (Kozusko et al, 2018), collagen (Cruz-Neves et al, 2017), hyaluronic acid, nHA (Cruz-Neves et al, 2017), polymers (Olthof et al, 2018;Sarigol-Calamak & Hascicek, 2018), metal and some composites (Newman & Benoit, 2016) were often used to fabricate bionic scaffolds with osteogenesis drugs, factors or even cells carried on, like bone morphogenetic protein-2 (BMP-2) (Holzapfel et al, 2016;Lee et al, 2016;Martin & Bettencourt, 2018;Olthof et al, 2018). These implanted bone tissue engineering or bone regeneration materials can be explored as multifunctional materials to carry anti-osteolysis drugs or anti-osteolysis drug delivery systems.…”