Wounds or injuries resulting from burns, chronic disorders, and surgeries can lead to disability and pose significant challenges to healthcare systems worldwide. Despite numerous strategies and advancements in wound healing, managing chronic and deeper wounds remains an unmet therapeutic area due to difficulties in assessment and wound care management. Hence, the development of improved and cost-effective strategies holds great medical importance in the healthcare domain (Kolimi et al. 2022).
Extracellular matrix (ECM)-based approaches are emerging strategies for promoting wound healing. ECM is a non-cellular, dynamic, three-dimensional composite architecture composed of macromolecular components such as collagen, elastin, fibronectin, laminin, proteoglycans, glycosaminoglycans (GAGs), elastic fibres, matricellular proteins, enzymes, hyaluronan, growth factors, and other bioactive fragments and receptors. These biochemical factors provide signalling molecules that allow cells to sense, regulate, and interact with the matrix to control nearly all cellular functions—cell survival, cell polarity, cell differentiation, cell adhesion, cell proliferation, and cell migration (Karamanos et al. 2021).
ECM is locally synthesised and classified into the interstitial matrix and pericellular matrix. ECM-based scaffolds are excellent tools for delivering drugs/growth factors for tissue growth by upregulating and downregulating protein and growth factor synthesis (Pande et al. 2016). Naturally occurring connective tissue matrices are sourced from different species, including bovine, porcine, fish, etc. The preference for ECM sources is shifting from xenogenic to allogeneic due to the lower risk of undesirable immune responses. Among the various ECM-based strategies used for treating chronic wounds, tissue-derived ECM from human sources possesses advantages, retaining structural, biochemical, and functional integrity, along with adequate mechanical properties that provide biomolecular signals to cells, mimicking the native environment for easy host integration. Human-based ECM scaffold sources include dermal matrices, adipose matrices, cardiac matrices, skeletal matrices, tendon ECM, urinary bladder matrices, small intestine submucosa ECM, and placenta-derived ECM, etc. (Xing et al. 2020).
The human placenta is a unique temporary organ that has been used for therapeutic purposes in the form of cell or tissue transplants and extracts, owing to its regenerative properties. Recently, interest in the placental disc as a biomaterial has increased due to its biochemical composition, physiology, and unique function. The extracellular matrix of the placenta offers a favourable environment for wound healing. The biocompatible ECM scaffold from the placenta can facilitate proper tissue remodelling and overcome the limitations of normal repair (Ganesh et al. 2023; Roy et al. 2022). The components reported in the placental connective tissue matrix, placental extract, and their roles in wound healing are presented in Table 1. Aqueous extract from the human placenta has demonstrated effective therapeutic potential, and scientifically proven properties of placental extract include anti-inflammatory activity, antioxidant activity, anti-platelet aggregation activity, anti-melanogenesis activity, wound healing activity, and antiviral properties. It has also shown therapeutic potential in various conditions such as periodontal therapy, oral and maxillofacial surgery, complex regional pain syndrome, fibromyalgia syndrome, osteoarthritis, contact hypersensitivity, chronic fatigue syndrome, improving long-lasting hyperpigmentation, lung tissue protection, and hair growth (Chakraborty et al. 2012; Liu et al. 2015; Devarampati et al. 2022; Nishan 2020; Cho and Park 2016; Park and Cho 2020; Gwam et al. 2019; Samiei et al. 2016; Kim et al. 2010; Park et al. 2016; Noh et al. 2016; Kumar et al. 2003; Phonchai et al. 2019; Kwon et al. 2015; Joshi et al. 2020).
Combination products/therapies have gained significant attention in pharmaceuticals, biopharmaceuticals, and regenerative therapies. A combination product includes two or more regulated components, such as drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity (Combination Product Definition Combination Product Types by USFDA 2023). Given the complexity of chronic and deeper wounds, a single intervention is less likely to yield improved patient outcomes. Instead, combination therapies seem necessary. Ideally, the product should be biocompatible, biodegradable, and modifiable according to the injury. To achieve a paste-like consistency or to make a particular placental connective tissue matrix flowable, sterile saline or autologous fluids are mixed with them before application. Instead of using saline, mixing human placental extract with placental connective tissue matrix could maximise the available quantities of bioactive molecules to enhance therapeutic efficacy and can be effectively applied in irregular cavities. We developed a combination product known as dHPCTM-HPE (decellularized placental connective tissue matrix - human placental extract) and examined the levels of structural and bioactive components present in unprocessed placental tissue, decellularized placental connective tissue matrix, placental extract, and the combination product dHPCTM-HPE.